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BACKGROUND: Trastuzumab deruxtecan (T-DXd) has been approved for the treatment of human epidermal growth factor receptor-2 (HER2)-positive gastric cancer and other indications in several countries and is considered moderately or highly emetogenic. The management of nausea and vomiting associated with T-DXd treatment has not been fully evaluated and the effectiveness of conventional prophylaxis remains unknown. METHODS: This open-label, randomized, multicenter, phase 2 study aimed to investigate the optimal antiemetic therapy for Japanese patients with gastric cancer undergoing T-DXd treatment. Patients were randomized to a doublet regimen group (dexamethasone and palonosetron) or triplet regimen group (aprepitant, dexamethasone, and palonosetron) at a ratio of one to one, stratified by sex, gastrectomy status, and study institution. Both antiemetic treatments were administered from day 1 before T-DXd administration, and emetic events and nausea were observed for 21 days. The primary endpoint was the antiemetic complete response (CR) rate to assess control for emetic events based on voluntary patient-reported outcomes (PROs) during cycle 1 (1-21 days). RESULTS: Of the 60 enrolled patients, 58 were eligible for inclusion in this analysis (29 patients in each regimen group). The overall CR rates for the doublet and triplet regimens were 41.4% (12/29 patients) and 37.9% (11/29 patients), respectively, and neither regimen met the pre-specified threshold (> 18/29 patients). The CR rate in the acute phase (0-24 h) was 86.2% (25/29 patients) for both regimens, and the CR rates in the delayed phase (2-21 days) were 41.4% (12/29 patients) and 37.9% (11/29 patients) for the doublet and triplet regimens, respectively. CONCLUSIONS: Given that the primary endpoint was not met, further research is needed to better characterize nausea and vomiting with T-DXd to tailor an anti-emetic regimen that suits the needs of the patients.

DOI： 10.1007/s10147-025-02748-8

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BACKGROUND/AIM: Malnutrition is a reported prognostic factor in patients with cancer. The controlling nutritional status (CONUT) score, an index calculated from routine laboratory tests, is correlated with the prognosis of various cancers. This study examined the relationship between the CONUT score and prognosis of patients with gastric cancer (GC) after radical gastrectomy. PATIENTS AND METHODS: Patients with GC who underwent curative gastrectomy were retrospectively reviewed. Patient characteristics, laboratory data, pathological findings, perioperative clinical course, and survival outcomes were recorded. The CONUT score was calculated using serum albumin (mg/dl), total cholesterol (mg/dl), and lymphocyte count (cells/mm3). Based on previous studies, patients were categorized into normal (CONUT score <2) and malnutrition (CONUT score ≥2) groups. Prognostic factors were compared between the groups. RESULTS: In total, 155 patients were included (median age, 69 years; male, n=110; female, n=45). Five-year overall survival (OS) was significantly lower in the malnutrition group (malnutrition group, 42.2%; normal group, 82.7% p<0.001). A multivariate analysis identified the CONUT score as an independent prognostic factor for OS [HR=2.506; 95% confidence interval (CI)=1.288-4.873, p=0.007]. Similar results were obtained for recurrence-free survival (RFS). Additionally, postoperative complications were more frequent (malnutrition group, 44.2%; normal group, 25.9%; p=0.027) and the chemotherapy introduction rate for pStage III or III was lower (malnutrition group, 55.6%; normal group, 78.8%, p=0.054) in the malnutrition group. CONCLUSION: The CONUT score may be an independent prognostic factor for OS and RFS in patients with GC after curative gastrectomy. CONUT scores of ≥2 were associated with higher postoperative complications and lower chemotherapy rates, which may contribute to a poor prognosis.

DOI： 10.21873/anticanres.17512

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BACKGROUND: The postoperative impact of short-term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1 month after surgery in determining postoperative survival and recurrence rates in patients with GC. METHODS: We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1 month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v-ATL), and subcutaneous ATL (s-ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v-ATL and s-ATL measurements. RESULTS: Patients with higher v-ATL and s-ATL had lower overall survival (OS) and recurrence-free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16-4.42; and P = 0.02) and RFS (HR 2.51; 95% CI 1.34-4.71; and P = 0.004) rates. CONCLUSION: A reduction in adipose tissue volume shortly after surgery (1 month) could potentially indicate an increased risk of recurrence and mortality in patients with GC.

DOI： 10.1002/wjs.12370

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BACKGROUND/AIM: In several previous studies, the modified advanced lung cancer inflammation index (mALI) has been reported to be a useful prognostic factor in non-small cell lung cancer. This study aimed to demonstrate the relationship between mALI and the oncological prognosis of patients with esophageal cancer (EC) who underwent curative treatment and to clarify the underlying mechanism. PATIENTS AND METHODS: We retrospectively followed up patients who underwent curative resection of esophageal cancer at Yokohama City University between 2000 and 2020 and extracted clinical data from their medical records. mALI was defined as follows: mALI=[L3 muscle index (L3MI) (cm2/m2)×albumin (g/l)]/neutrophil-to-lymphocyte ratio (NLR) [neutrophil count÷lymphocyte count]. RESULTS: A total of 196 patients were selected for this study, and the cutoff value for mALI was set separately for male and females. When the cutoff value was set at 10 for males and 12 for females, 84 patients were assigned to the mALI-low group and 112 patients were assigned to the mALI-high group. A survival analysis revealed that the 5-year overall survival (OS) rate was 50.3% in the mALI-low group and 62.5% in the mALI-high group (p=0.014). A multivariate analysis of OS revealed that mALI was an independent prognostic factor. The 5-year recurrence-free survival (RFS) rates were 33.0% in the mALI-low group and 44.9% in the mALI-high group (p=0.044). The multivariate analysis of RFS revealed that mALI was an independent prognostic factor. In addition, the mALI-low group had a higher rate of hematogenous metastasis than the mALI-high group. CONCLUSION: mALI is associated with the oncological prognosis of patients with EC who have undergone radical resection via several mechanisms and is a useful prognostic factor.

DOI： 10.21873/invivo.14013

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BACKGROUND/AIM: The randomized phase II COMPASS trial revealed that neither the regimen nor the number of courses of preoperative neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) significantly influence overall survival (OS). However, the impact of NAC regimens on OS may vary from patient to patient. The aim of this study was to identify biomarkers that can predict more appropriate individualized NAC regimens for improved prognosis using biopsy specimens from the COMPASS trial. PATIENTS AND METHODS: RNA was extracted from endoscopic biopsy specimens of primary tumors obtained prior to NAC and real-time PCR analysis of 127 genes was conducted to identify those significantly affecting survival in the context of specific NAC regimens. RESULTS: THBS1, MSI1, and IGF2BP3 were identified as significant factors for stratifying survival among different NAC regimens, with statistically significantly interaction p values. Immunohistochemical analysis confirmed that the protein levels of THBS1, MSI1, and IGF2BP3 strongly correlated with their gene expression levels, validating these proteins as reliable biomarkers. CONCLUSION: This study effectively identified THBS1, MSI1, and IGF2BP3 as promising biomarkers for personalizing NAC regimens in patients with locally advanced GC. By tailoring NAC based on these biomarkers, it is possible to enhance survival outcomes and advance personalized treatment strategies. The findings underscore the potential for incorporating biomarker-guided approaches into clinical trials, aiming to refine and optimize NAC regimens for improved patient-specific treatment efficacy.

DOI： 10.21873/anticanres.17320

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BACKGROUND/AIM: The function of the S-100 protein family member hornerin (HRNR) in gastric cancer (GC) tissues is largely unknown. We researched the clinical significance of HRNR expression in GC tissues of patients with pathological (p)Stage II/III GC after curative resection. PATIENTS AND METHODS: We included patients with pStage II/III GC who underwent curative gastrectomy (n=253). Expression levels of HRNR in GC tissue and in the adjacent normal mucosa were determined using quantitative real-time polymerase chain reaction. Clinicopathological features and overall survival (OS) were compared in patients with different HRNR expression levels in GC tissue. RESULTS: HRNR expression levels were significantly higher in GC tissues than in the adjacent normal mucosa. HRNR expression level in GC tissue showed sex differences. The 5-year OS rate in the high-HRNR expression group was significantly worse than that in the low-expression group (5-year survival 53.6% vs. 74.9%; p=0.004). Furthermore, on multivariate analysis, high-HRNR expression was an independent predictor of poor OS (hazard ratio=1.534; 95% confidence interval=1.130-2.618; p=0.011). CONCLUSION: In patients with pStage II/III GC after curative gastrectomy, HRNR expression in GC tissue may be a useful prognostic marker.

DOI： 10.21873/anticanres.17287

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BACKGROUND/AIM: Granzyme B (GZMB) is mainly produced by natural killer (NK) cells and activated CD8-positive T cells to induce tumor cell apoptosis. We analyzed the significance of GZMB expression in gastric cancer (GC) tissues from patients with pathological (p)Stage II/III GC after curative resection. PATIENTS AND METHODS: Patients with pStage II/III GC who received curative resection (n=253) were included and the expression levels of GZMB in GC tissues and in the adjacent normal mucosa were measured using quantitative real-time polymerase chain reaction. The expression levels in GC tissues and clinicopathological features and overall survival (OS) were compared in these patients. RESULTS: GZMB expression levels were significantly higher in GC tissues than in the adjacent normal mucosa. GZMB expression levels in GC tissues were not associated with any clinicopathological features. The 5-year OS rate in the high-GZMB expression group was significantly better than that in the low-expression group (5-year survival rate 72.0% vs. 55.7%; p=0.009). Furthermore, on multivariate analysis, high-GZMB expression was an independent factor for better OS (hazard ratio=0.652; 95% confidence interval=0.432-0.987; p=0.043). CONCLUSION: In patients with locally advanced GC after curative resection, GZMB expression in GC tissue may be a useful prognostic marker.

DOI： 10.21873/anticanres.17282

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The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC.

DOI： 10.3892/ol.2024.14591

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BACKGROUND/AIM: The Inflammatory Burden Index (IBI) has been reported as a novel prognostic indicator in several cancers and diseases. However, research on the IBI in patients with gastric cancer (GC) after gastrectomy is insufficient. This study investigated the utility of the preoperative IBI as a prognostic indicator in patients with GC. PATIENTS AND METHODS: This retrospective study enrolled 459 patients undergoing gastrectomy for GC between 2013 and 2017 at the Kanagawa Cancer Center, Kanagawa, Japan. The IBI was calculated from preoperative blood test data. We evaluated the relationship between the preoperative IBI and clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC, using propensity score matched analysis. RESULTS: Regarding the association between IBI and clinicopathologic features, the high-IBI group was significantly older and had more lymphatic invasion and more progressive pT status than the low-IBI group before propensity score-matched analysis. OS and RFS after curative surgery were significantly lower in patients with a high IBI than in those with a low IBI (77.5% vs. 86.1%; p=0.02 and 74.3% vs. 85.1%; p=0.03, respectively). Multivariate analysis identified high IBI as an independent predictor of both OS and RFS. CONCLUSION: Preoperative IBI may serve as a valuable prognostic indicator for patients undergoing curative gastrectomy for GC.

DOI： 10.21873/anticanres.17228

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BACKGROUND/AIM: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex. PATIENTS AND METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis. RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females. CONCLUSION: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.

DOI： 10.21873/anticanres.17172

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The prognostic significance of inflammation, immune response and nutritional status in patients with cancer is well-documented. The advanced lung cancer inflammation index (ALI) has emerged as a novel prognostic indicator, reflecting both inflammation and nutritional status. This study aimed to assess the prognostic relevance of preoperative ALI in patients with gastric cancer (GC). Data of 459 patients who underwent curative gastrectomy for GC between December 2013 and November 2017 at the Kanagawa Cancer Center (Yokohama, Japan) were retrospectively analyzed. Preoperative ALI was calculated from blood tests. Patients were divided into the high- and low-ALI groups. This study investigated the association between preoperative ALI, clinicopathological features, overall survival (OS) and relapse-free survival (RFS) after propensity-matched analysis. Comparative analysis revealed that patients in the low-ALI group tended to be older, were predominantly female, had lower body mass index and had a higher incidence of lymphatic invasion compared with those in the high-ALI group before propensity-matched analysis. Notably, the low-ALI group exhibited significantly reduced OS and RFS post-gastrectomy (85.5% vs. 93.8%, P=0.01; and 82.1% vs. 91.8%, P=0.02, respectively). Multivariate analysis identified low ALI as an independent prognostic factor for both OS and RFS. In conclusion, preoperative ALI could provide a valuable prognostic tool for patients with GC undergoing curative resection, offering insights into patient survival outcomes based on their inflammatory and nutritional status.

DOI： 10.3892/ol.2024.14418

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BACKGROUND/AIM: In East Asia, the standard treatment for resectable advanced gastric cancer involves gastrectomy and postoperative adjuvant chemotherapy; nevertheless, neoadjuvant chemotherapy is also expected to improve survival rates. However, it remains unclear whether the same criteria can be used to select adjuvant chemotherapy for patients treated with neoadjuvant chemotherapy, or how survival varies between post-chemotherapy pathological Stage (ypStage) and pathological Stage without chemotherapy (pStage). This study evaluated the long-term outcomes of ypStage and pStage in gastric cancers and investigated the optimal intensity of adjuvant chemotherapy for patients who have received preoperative chemotherapy. PATIENTS AND METHODS: From January 2007 to November 2019, 1,585 patients underwent radical gastrectomy for gastric cancer at the Kanagawa Cancer Center. The patient background was adjusted by propensity score matching, and recurrence-free survival was compared between the two groups. In addition, a prognostic factor analysis was conducted for each yp/pStage. RESULTS: The 5-year recurrence-free survival rates for yp/pStage I were 77.1% and 90.9%, respectively, with no significant difference (p=0.342). The 5-year recurrence-free survival rates for yp/pStage II were 50.4% and 69.1%, respectively, with no significant difference (p=0.062). The 5-year recurrence-free survival rates for yp/pStage III were 42.9% and 68.7%, respectively, with a significant difference observed (p=0.016). In the prognostic factor analysis for each stage, the presence or absence of preoperative chemotherapy was selected as an independent prognostic factor for yp/pStage I [hazard ratio (HR)=17.72; p=0.001] and yp/pStage II (HR=2.655, p=0.003). CONCLUSION: ypStage tends to have a worse prognosis than pStage, and further development of multidisciplinary treatment is necessary.

DOI： 10.21873/anticanres.17073

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BACKGROUND/AIM: The prognostic immune and nutritional index (PINI) was developed and reported as a promising prognostic factor. This study aimed to clarify the clinical impact of the PINI in gastric cancer (GC) patients who received curative treatment. PATIENTS AND METHODS: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The PINI was calculated by dividing the serum albumin concentration (g/dl) by the serum monocyte concentration. Both measurements were performed prior to surgery. RESULTS: A total of 262 patients were included in this study. Based on the 3- and 5-year overall survival (OS), we set the cutoff value of the PINI at 3.4 in the present study. The 3- and 5-year OS rates were 69.0% and 66.1%, respectively, in the PINI-low group and 90.5% and 82.8% in the PINI-high group. There were significant differences between the two groups (p<0.001). A multivariate analysis of factors associated with OS identified PINI as an independent prognostic factor (hazard ratio=1.996; 95% confidence interval=1.096-3.636, p=0.024). Similar results were observed for RFS. In addition, the PINI status affected the recurrence pattern, postoperative anastomotic leakage, and the introduction of postoperative adjuvant chemotherapy. CONCLUSION: The PINI is a promising nutritional and inflammatory marker for patients with GC and might be a useful marker for the treatment and management of patients with GC.

DOI： 10.21873/anticanres.17030

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BACKGROUND/AIM: Recently, the prognostic immune and nutritional index (PINI) was developed and reported to be a promising nutritional and inflammatory prognostic marker. The aim of the present study was to clarify the clinical impact of the PINI for esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: We conducted a retrospective review of medical records and collected data on consecutive esophageal cancer patients who underwent curative resection at Yokohama City University between 2005 and 2020. The PINI was calculated by dividing the serum ALB concentration (g/dl) by the serum monocyte concentration, both of which were measured before surgery. RESULTS: A total of 180 patients were included in this study. The cutoff value of the PINI was 3.0 in the present study. The 3- and 5-year overall survival rates were 45.2% and 33.5%, respectively, in the PINI-low subgroup, and 69.1% and 61.8%, respectively, in the PINI-high subgroup. A multivariate analysis demonstrated that the PINI was an independent prognostic factor for overall survival (hazard ratio=2.091, 95% confidence interval=1.287-3.399, p=0.003). Similar results were observed for recurrence-free survival. When comparing the sites of recurrence between the two groups, the incidence of hematological recurrence was significantly greater in the PINI-low subgroup compared to the PINI-high subgroup (46.8% vs. 21.1%, p<0.001). CONCLUSION: The PINI is a promising nutritional and inflammatory marker for esophageal cancer patients. The PINI might be a useful marker for the treatment and management of esophageal cancer patients.

DOI： 10.21873/anticanres.17025

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BACKGROUND/AIM: The tryptophanyl-tRNA synthetase 1 gene (WARS1), encodes a tryptophan-tRNA synthetase involved in the amino acidification of tryptophan-tRNA and has been reported to be involved in cancer cell growth, metastasis promotion, and drug resistance in a variety of cancers. This study investigated the clinical significance of WARS1 expression as a biomarker in gastric cancer tissues obtained from patients with locally advanced gastric cancer (GC) who underwent radical resection. PATIENTS AND METHODS: WARS1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection was determined using quantitative polymerase chain reaction (PCR). Association of WARS1 expression levels, categorized into high and low expression based on the median expression levels, with clinicopathological factors and overall survival (OS) of these patients was assessed. RESULTS: The low-WARS1 expression group had significantly higher serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage than did the high-WARS1 expression group. OS was significantly worse in the low- than in the high-WARS1 expression group (5-year survival 52.2% vs. 75.9%; p=0.0001). Furthermore, in multivariate analysis, low WARS1 expression was an independent predictor for poor OS (hazard ratio=2.101; 95% confidence interval=1.328-3.322; p=0.002). CONCLUSION: In patients with locally advanced GC, after curative resection, WARS1 expression in GC tissue may be a useful prognostic marker.

DOI： 10.21873/anticanres.16857

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BACKGROUND/AIM: This study aimed to compare dietary intake (DI) after gastrectomy for gastric cancer between patients with (C group) and without (NC group) postoperative surgical complications. PATIENTS AND METHODS: This prospective observational study enrolled patients who underwent gastrectomy for gastric cancer. DI was assessed using a food frequency questionnaire with 82 food items (FFQW82) during nutritional counseling before surgery and at one and three months after surgery. RESULTS: A total of 225 patients participated in this study. Of the 225 patients, 193 had no postoperative complications, and 32 had postoperative complications (Clavien-Dindo grade ≥2). The median DI at 1 month postoperatively was 1508 kcal/day in the NC group and 1,470.5 kcal/day in the C group (p=0.175). The median DI at 3 months postoperatively was 1,623 kcal/day in the NC group and 1575 kcal/day in the C group (p=0.473). There was a significant difference between the NC and C groups in the rate of decrease in DI at one month (median: -8.44% vs. -15.37%, p=0.032) and at three months postoperatively (median: -3.58% vs. -6.12%, p=0.038). CONCLUSION: There was a statistically significant difference in the rate of decrease in DI after gastrectomy between the C and NC groups at 1 and 3 months postoperatively. Our results suggest that patients with postoperative surgical complications require additional nutritional treatment for decreased DI.

DOI： 10.21873/anticanres.16876

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BACKGROUND/AIM: Pregnancy zone protein (PZP), encoded by PZP, belongs to the α-2-macroglobulin superfamily, and plays an important role in inflammatory responses and immune cell activation in cancer. However, the relationship between gastric cancer (GC) and PZP is poorly studied. This study investigated the clinical significance of PZP expression in GC tissues of patients with locally advanced GC after curative resection. PATIENTS AND METHODS: Using quantitative polymerase chain reaction, we measured PZP expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels of PZP in GC tissues and adjacent normal gastric mucosa and examined the relationship of PZP expression in GC tissues with clinicopathological factors and overall survival (OS). RESULTS: PZP expression was significantly associated with histology, venous invasion, and pathological stage. The high PZP expression group had significantly worse OS than did the low expression group (5-year survival 48.6% vs. 68.5%, p=0.0003). Furthermore, in multivariate analysis, high PZP expression was an independent factor for poor OS (hazard ratio=1.984, 95% confidence interval=1.307-3.012, p=0.0013). CONCLUSION: In post-curative resection patients with locally advanced GC, PZP expression in GC tissue may be a useful prognostic marker.

DOI： 10.21873/anticanres.16820

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BACKGROUND/AIM: Chitinase-3-like protein 1 (CHI3L1), encoded by CHI3L1, is thought to be involved in growth, invasion, migration, and resistance to chemotherapy in cancer. This study aimed to investigate the clinical significance of CHI3L1 expression as a biomarker in gastric cancer (GC) tissues of patients with locally advanced GC after curative resection. PATIENTS AND METHODS: Quantitative polymerase chain reaction (PCR) was used to determined CHI3L1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels in GC tissues and adjacent normal gastric mucosa, and examined the relationship between expression in GC tissues and clinicopathological factors and overall survival (OS) in these patients. RESULTS: CHI3L1 expression was significantly associated with lymph-node metastasis and venous invasion. OS rate was significantly lower in the high- than in the low-CHI3L1 expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high CHI3L1 gene expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001). CONCLUSION: In patients with locally advanced GC after curative resection, expression of the CHI3L1 in GC tissue may be a useful prognostic marker.

DOI： 10.21873/anticanres.16813

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BACKGROUND/AIM: The asialoglycoprotein receptor 2 gene (ASGR2) encodes a subunit of the asialoglycoprotein receptor, a transmembrane protein, which has recently been reported to be involved in gastric cancer (GC) progression. This study aimed to investigate the clinical significance of ASGR2 expression in GC tissues of patients with locally advanced gastric cancer (LAGC) after curative resection. PATIENTS AND METHODS: ASGR2 expression was measured in GC tissues and adjacent normal gastric mucosa in 253 patients with pStage II/III GC who underwent curative resection, by using quantitative polymerase chain reaction. We compared the expression levels in GC tissues and adjacent normal stomach mucosa, and evaluated the relationship of its expression in GC tissues with clinicopathological factors and overall survival (OS). RESULTS: ASGR2 expression was significantly associated with lymph node metastasis and venous invasion. The high ASGR2-expression group demonstrated significantly lower survival than the low expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high ASGR2 expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001). CONCLUSION: ASGR2 expression in GC tissues may be a useful prognostic marker in patients with LAGC after curative resection.

DOI： 10.21873/anticanres.16824

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BACKGROUND/AIM: Dietary intake (DI) loss after gastrectomy is a serious problem for patients with gastric cancer. This study compared the dietary intake after surgery in patients with early gastric cancer who received laparoscopic distal gastrectomy (LDG) versus those who underwent conventional open distal gastrectomy (ODG). PATIENTS AND METHODS: This was a prospective, observational study enrolling patients who underwent gastrectomy for gastric cancer. Dietary intake was assessed using the food frequency questionnaire with eighty-two food items (FFQW82) at nutritional counseling before surgery and one and three months after surgery. RESULTS: A total of 118 patients were included. Among them, 69 (58.5%) were male, and 49 (41.5%) were female. Seventy-five (63.6%) received LDG, and 43 (36.4%) received ODG. At 1 month postoperatively, the median DI in the LDG group was 1,540 (1,014-2,195) kcal/day, whereas that in the ODG group was 1547 (986-2,143) kcal/day (p=0.891). At 3 months postoperatively, the median DI in the LDG group was 1,624 (1,050-2,443) kcal/day, and that in the ODG group was 1,652 (917-2,144) kcal/day (p=0.749). There was no significant difference in the DI loss rate at 1 month (median: -8.2% vs. -9.3%, p=0.398) and 3 months (median: -3.2% vs. -3.7%, p=0.635) between the LDG and ODG groups. CONCLUSION: Minimally invasive laparoscopic surgery may not prevent postoperative DI loss after distal gastrectomy. Therefore, methods other than laparoscopic surgery are needed to prevent post-gastrectomy DI loss.

DOI： 10.21873/anticanres.16826

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BACKGROUND/AIM: The perioperative nutritional status has recently been reported to influence the prognosis of various types of cancer. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and overall survival (OS) and recurrence-free survival (RFS) in patients with esophageal cancer who received radical and adjuvant therapy. PATIENTS AND METHODS: Patients who underwent radical resection for esophageal cancer at our hospital (n=187) were included. Background characteristics, surgical factors, and OS were examined retrospectively. The GNRI was calculated using preoperative values, with GNRI <98 classified as low-GNRI. RESULTS: Seventy-five and 112 patients were classified into the GNRI-low and -high groups, respectively. The 3- and 5-year OS rates were 75.7% and 66.7%, respectively, in the GNRI-high group and 43.2% and 36.7% in the GNRI-low group; the difference was statistically significant (p<0.001). In the univariate and multivariate analyses, low-GNRI was selected as a risk factor for OS. The hazard ratio for low-GNRI was 2.184 (95% confidence interval=1.361-3.508, p=0.001). The 5-year RFS rate in the high- and low-GNRI groups was 54.6% and 25.0%, respectively (p=0.001). In the univariate and multivariate analyses, low-GNRI was a risk factor for RFS. The hazard ratio for low-GNRI was 1.704 (95%CI=1.121-2.590, p=0.013). Regarding the type of recurrence, lymph node recurrence was significantly more common in the low-GNRI group (p=0.008). CONCLUSION: Low-GNRI was an independent risk factor for OS and RFS after radical resection of esophageal cancer. The preoperative GNRI may be a useful prognostic factor after esophageal cancer surgery.

DOI： 10.21873/anticanres.16816

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BACKGROUND/AIM: Pretreatment fibrinogen levels are a promising prognostic marker for some malignancies. The aim of the present study was to evaluate the clinical impact of fibrinogen levels before treatment in patients with esophageal cancer who underwent curative resection. PATIENTS AND METHODS: This study included 123 patients who underwent curative treatment for esophageal cancer between 2005 and 2020. The prognosis and clinicopathological parameters in the high fibrinogen and low fibrinogen groups were analyzed. RESULTS: Overall survival (OS) stratified by individual clinical factors was compared using the log-rank test, and a significant difference was observed when a pretreatment fibrinogen level of 400 g/dl was used as a cutoff value. The comparison of the patient background factors between the high fibrinogen (400 g/dl) and low fibrinogen (<400 g/dl) groups revealed significant differences in pathological T status and lymph node metastasis. In the low fibrinogen group, the OS rates at 3 and 5 years after surgery (71.4% and 58.1%, respectively) were significantly higher than those in the high fibrinogen group (38.3% and 32.4%, respectively). Univariate and multivariate analyses for OS showed that the fibrinogen level prior to treatment was a significant prognostic factor. Similar results were observed for recurrence-free survival. In addition, when the first recurrence site was compared, there were marginally significant differences in hematologic recurrence. CONCLUSION: Pretreatment fibrinogen levels are a significant risk factor in patients with esophageal cancer. Therefore, pretreatment fibrinogen levels are a promising prognostic factor for patients with esophageal cancer.

DOI： 10.21873/anticanres.16808

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BACKGROUND/AIM: A new modified nutritional risk index (mNRI), calculated using serum albumin (g/l)+body mass index (BMI) [weight (kg_/height2 (m2)], is a good predictor of postoperative complications and cancer survival. However, no study has used this index in patients with gastric cancer (GC). Therefore, we aimed to investigate the clinical significance of the preoperative mNRI values in patients with GC who underwent curative resection. PATIENTS AND METHODS: We examined 449 patients who underwent curative resection for GC at Kanagawa Cancer Center between 2013 and 2017. The mNRI cutoff value obtained using a receiver operating characteristic analysis was 23.31. Patients were divided into high and low mNRI groups according to the cutoff value, and the clinicopathological characteristics and outcomes were compared between the two groups. RESULTS: In terms of clinicopathological characteristics, the high mNRI group had a higher proportion of men, higher BMI, and a higher proportion of patients with American Society of Anesthesiologists physical status class 2/3 compared with the low mNRI group; the low mNRI group had significantly worse 5-year recurrence-free survival (RFS) and overall survival (OS) than the high mNRI group (OS, p=0.005) (OS, p=0.006; RFS, p=0.018) did. In the multivariate analysis, a low mNRI was an independent predictor of OS (p=0.006) and RFS (p=0.013). CONCLUSION: Preoperative mNRI may be a useful recurrence and prognostic biomarker in patients with GC who have undergone curative resection.

DOI： 10.21873/invivo.13434

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BACKGROUND/AIM: Radical esophagectomy after preoperative neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, careful treatment selection is required when considering organ function in elderly patients. Prealbumin, a rapid turnover protein, is a short-term dynamic nutritional index, and its relationship with long-term postoperative survival in various cancers has been previously reported. However, the association between serum prealbumin level before NAC and survival in elderly patients remains unclear. This study investigated the clinical significance of prealbumin level measurement before NAC in elderly patients with locally advanced ESCC who underwent surgery after NAC. PATIENTS AND METHODS: Eighty patients aged ≥65 years diagnosed with cStage II/III ESCC and undergoing radical esophagectomy after cisplatin and 5-fluorouracil therapy as NAC, were included. The cutoff value of the serum prealbumin level before NAC was set at 18.2 mg/dl using receiver operating characteristic curve analysis, and postoperative complications, recurrence, and overall survival were compared between the low and high prealbumin groups. RESULTS: There were no differences in patient background, clinicopathological characteristics, postoperative complications, or recurrence-free survival between the two groups. Overall survival (OS) was significantly worse in the low prealbumin group than in the high prealbumin group (5-year survival, 33.3% vs. 67.0%; p=0.0341). Furthermore, on univariate and multivariate analysis, low prealbumin level was an independent poor OS factor (p=0.036). CONCLUSION: In elderly patients with locally advanced ESCC, serum prealbumin level before NAC may be a useful prognostic factor and may be important in selecting a treatment strategy that considers individual organ function.

DOI： 10.21873/invivo.13443

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BACKGROUND/AIM: Based on gastric shape, patients with gastric cancer can be divided into storage (hook-shaped and ptotic stomach) and reverse outflow (steer-horn and cascade stomach) groups. In patients with gastric cancer, postoperative loss of lean body mass (LBM) is associated with a poor prognosis. This study investigated the influence of preoperative gastric shape on LBM loss 1 month after curative distal gastrectomy. PATIENTS AND METHODS: Between May 2011 and May 2019, we enrolled 487 patients with pathological stage IA/IB/IIA gastric cancer who underwent curative distal gastrectomy and did not receive adjuvant chemotherapy. Patients were divided into storage (n=370) and outflow (n=117) groups according to whether barium was stored in the stomach during the preoperative fluoroscopic examination. Clinicopathological features, LBM 1 month after gastrectomy, and predictors of postoperative LBM loss were compared between the groups using multivariable logistic regression. RESULTS: The incidence of >5% LBM loss and >7.5% body weight loss 1 month postoperatively were significantly higher in the storage group than in the outflow group (p=0.003 and p=0.009, respectively). Multivariable analysis revealed that gastric shape [odds ratio (OR)=3.30, 95% confidence interval (CI)=1.95-5.59, p<0.001], male sex (OR=3.20, 95% CI=2.07-4.96, p<0.001), and Roux-en-Y reconstruction (OR=1.69, 95% CI=1.08-2.64, p=0.02) were independent predictors of LBM loss. Postoperative dietary problems, especially dumping syndrome, diarrhea, and reflux were more common in the storage group (p<0.001). CONCLUSION: Gastric shape may be a useful independent predictor of postoperative LBM loss in patients with gastric cancer undergoing distal gastrectomy.

DOI： 10.21873/invivo.13458

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BACKGROUND/AIM: Radical resection after preoperative adjuvant chemotherapy (NAC) is a standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LAESCC), but its outcome remains unsatisfactory. In order to develop a personalized treatment program for LAES, we herein compared the survival prediction utility of five pre-NAC nutritional, inflammatory, and immune indexes in patients with LAESCC. PATIENTS AND METHODS: We evaluated the survival of 203 patients with LAESCC who underwent radical resection after NAC from January 2011 to September 2019 for the following representative pre-NAC nutritional, inflammatory, and immune indices: modified Glasgow Prognostic Score, Prognostic Nutritional Index, C-reactive protein/albumin ratio, serum neutrophil/lymphocyte ratio, and Geriatric Nutrition Risk Index (GNRI) were evaluated for their impact on survival. RESULTS: Of the five indices, GNRI was the best predictor of survival as determined by the area under the curve (p<0.05). When patients were divided into three groups according to the nutritional risk assessment of Bouillanne et al. using the pre-NAC GNRI, the 5-year overall survival (OS) and recurrence-free survival (RFS) were significantly stratified (p<0.001). On multivariate analysis, the GNRI independently identified a poor OS group [group 1: hazard ratio (HR)=2.598, p=0.002; group 2: HR=6.257, p<0.001] and a high recurrence risk group (group 1: HR=1.967, p=0.016; group 2: HR=4.467, p<0.001). CONCLUSION: In patients with LAESCC, GNRI may be the most accurate, reliable, and useful prognostic factor among the five major systemic inflammatory and nutritional indices.

DOI： 10.21873/invivo.13514

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BACKGROUND/AIM: Systemic immune-inflammation index (SII) was developed and evaluated for various malignancies. This study evaluated the clinical impact of the SII in patients with gastric cancer (GC) who received curative treatment. PATIENTS AND METHODS: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were chosen consecutively based on their medical records. SII was calculated as follows: platelet (cell/mm3 ×103)× neutrophil (cell/mm3)/lymphocyte (cell/mm3). Three measurements were obtained preoperatively. RESULTS: In total, 258 patients were enrolled in this study. Based on the 3- and 5-year survival rates and previous studies, we set the cutoff value of the SII to 550. The 258 patients were classified into the SII-low (n=152) and SII-high (n=106) groups, respectively. The 3- and 5-year overall survival (OS) rates were 82.6% and 78.7%, respectively, in the SII-low group and 74.5% and 61.9%, respectively, in the SII-high group. There were significant differences between the two groups (p<0.001). In the multivariate analysis of factors associated with OS, the SII was identified as an independent prognostic factor (hazard ratio=1.816; 95% confidence interval=1.075-3.069, p=0.026). Similar results were observed for recurrence-free survival. In addition, the incidence of postoperative surgical complications was 30.9% in the SII-low group and 45.2% in the SII-high group (p=0.019). CONCLUSION: The SII was an independent prognostic factor for GC. Thus, the SII may be a promising biomarker for the treatment and management of GC.

DOI： 10.21873/invivo.13657

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BACKGROUND/AIM: The aim of the present study was to evaluate the clinical impact of the Global Immune-Nutrition-Information Index (GINI) in patients with gastric cancer (GC) who received curative treatment and to clarify the potential of the GINI as a biomarker. PATIENTS AND METHODS: Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The GINI was calculated as follows: GINI=[C-reactive protein × platelet × monocyte × neutrophil]/[albumin × lymphocyte]. RESULTS: A total of 258 patients were included in this study. Of these, 169 patients were categorized into the GINI-low group and 89 into the GINI-high group using a cut-off value of 1,730. The three- and five-year overall survival (OS) rates were 86.4% and 78.4%, respectively, in the GINI-low group, and 66.4% and 58.3% in the GINI-high group (p<0.001). In a multivariate analysis for OS, the GINI was identified as an independent prognostic factor [hazard ratio (HR)=1.772; 95% confidence interval (CI)=1.053-2.979, p=0.031]. Similar results were observed for RFS. In addition, the GINI affected the perioperative clinical course, including postoperative surgical complications and postoperative adjuvant treatment. CONCLUSION: The GINI is a promising biomarker for the treatment and management of GC.

DOI： 10.21873/cdp.10353

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BACKGROUND/AIM: Recently, preoperative inflammatory, immune, and nutritional statuses have attracted attention as prognostic factors in post-curative gastrectomy patients with gastric cancer (GC). The usefulness of the C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic factor in patients with various cancers, has been reported. However, reports on the clinical significance of the CALLY index in patients with GC after gastrectomy remain inadequate. In this prospective study, we focused on the preoperative CALLY index and investigated its usefulness as a prognostic factor in patients with GC. PATIENTS AND METHODS: This study included 459 patients who underwent gastrectomy for GC between December 2013 and November 2017 at Kanagawa Cancer Center, Kanagawa, Japan. The preoperative CALLY index was calculated based on the preoperative blood test data. Patients were divided into high- and low-CALLY groups. The associations of the preoperative CALLY scores with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) after gastrectomy for GC were evaluated. RESULTS: The low-CALLY group was significantly older, had higher venous invasion, and a more progressive pStage than did the high-CALLY group. OS and RFS after gastrectomy in the low-CALLY group were significantly worse than those in the high-CALLY group (77.9% vs. 88.9%; p<0.001 and 73.8% vs. 87.1%; p<0.001, respectively). In the multivariate analysis, a low CALLY score was an independent prognostic factor of worse OS and RFS. CONCLUSION: Preoperative CALLY levels may be a useful prognostic predictor in patients with GC after curative gastrectomy.

DOI： 10.21873/invivo.13518

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BACKGROUND/AIM: This study aimed to investigate the differences in the postoperative dietary intake (DI) loss between men and women after radical resection for early gastric cancer (GC), and to identify effective nutritional support for both sexes. PATIENTS AND METHODS: This prospective, observational study enrolled patients who underwent gastrectomy for GC. DI was assessed using the food frequency questionnaire containing 82 food items (FFQW82) during nutritional counseling before surgery and one and three months postoperatively. RESULTS: The median preoperative DI of all participants was 1,856.3 kcal/day, and DI at 1 and 3 months were 1,532.5 kcal/day and 1,637 kcal/day, respectively. The median preoperative DI was 1805 kcal/day (1,300-2,330 kcal/day) and 1481 kcal/day (1,126-1,957 kcal/day) in men and women, respectively (p<0.0001). The median DI at 1 month was 1627 (1,101-2,195) kcal/day and 1,308 (986-1,915) kcal/day in men and women, respectively (p<0.0001). At 3 months postoperatively, the median DI was 1737 (1,130-2,443) kcal/day in men and 1428 (816-2,005) kcal/day in women (p<0.0001). However, there was no significant difference in the DI loss rate at 1 month (median: -9.7% vs. -9.3%, p=0.765) and 3 months (median: -3.5% vs. -4.8%, p=0.137) between men and women. CONCLUSION: Although the DI loss rate in men and women after gastrectomy for GC was almost similar, the postoperative DI and DI loss differed significantly. Therefore, differences in DI loss after gastrectomy between men and women should be considered while assessing the efficacy of additional nutritional support such as oral nutritional supplements after gastrectomy.

DOI： 10.21873/invivo.13638

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BACKGROUND: We investigated the impact of the prognostic nutritional index (PNI) on esophageal cancer survival and recurrence after curative treatment. METHODS: This study included 120 patients who underwent curative surgery followed by the adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: The PNI of 49 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The OS rates at three and five years after surgery were 47.4% and 36.0% in the PNI low group, respectively, and 62.5% and 56.5% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). The RFS rates at three and five years after surgery were 31.0% and 24.8% in the PNI low group, respectively, and 50.9% and 42.8% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). A multivariate analysis demonstrated that the PNI was a significant independent risk factor for the OS and a marginally significant independent risk factor forRFS. CONCLUSION: The PNI was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the PNI.

DOI： 10.4103/jcrt.JCRT_1595_20

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BACKGROUND/AIM: We evaluated the clinical impact of the Geriatric Nutritional Risk Index (GNRI) in patients who received curative treatment and perioperative adjuvant treatment. We also investigated the association between the GNRI and the clinicopathological features of patients with GC. PATIENTS AND METHODS: This study included 280 patients who underwent curative treatment for GC between 2005 and 2020. The prognosis and clinicopathological parameters of the high-GNRI and low-GNRI groups were compared. RESULTS: In the GNRI-high group, the overall survival (OS) rates at 3 and 5 years after surgery were significantly lower (82.7% and 77.9%, respectively) than those in the GNRI-low group (56.4% and 40.8%). The GNRI was selected for the final multivariate analysis model for OS. The GNRI was also a significant prognostic factor for recurrence-free survival (RFS). The RFS rates at 3 and 5 years after surgery were 79.1% and 74.8%, respectively, in the GNRI-high group, and 48.0% and 38.6% in the GNRI-low group. The GNRI was selected for the final multivariate analysis model for RFS. The GNRI was also found to affect the postoperative clinical course, including postoperative surgical complications and postoperative adjuvant chemotherapy. CONCLUSION: The GNRI may be a promising prognostic and predictive factor for gastric cancer. In the future, the GNRI may be used to select optimal treatment strategies.

DOI： 10.21873/anticanres.16763

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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BACKGROUND: An esophageal diverticulum is a relatively rare disease, with reports of treatment for esophageal cancer in the diverticulum even rarer. CASE PRESENTATION: The case involved a 72-year-old male with a chief complaint of dysphagia. He was diagnosed with an esophageal diverticulum (Zenker's diverticulum) measuring 10 cm in diameter. Five years later, an upper gastrointestinal endoscopy revealed an iodine-unstained 0-IIb lesion of 20 mm in diameter with type B1 vessels in the diverticulum. An endoscopic biopsy and CT revealed it to be squamous cell carcinoma, cT1a-EP/LPM N0 M0, cStage 0. Because the lesion was in the diverticulum and endoscopic resection was difficult with the risk of perforation, surgical resection was set as the course of treatment. Diverticulectomy was performed via a cervical approach, using a stapler, and the patient was discharged on the 16th day without any complications. The pathological diagnosis was pTis-EP, ly0, v0, R0. CONCLUSIONS: We think this case is very rare and diverticulectomy of early esophageal cancer in the diverticulum is available and safe.

DOI： 10.1186/s44215-023-00123-5

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BACKGROUND/AIM: The C-reactive protein to prealbumin ratio (CPAR) has been proposed and introduced in gastrointestinal cancer management. This study aimed to evaluate the clinical impact of the CPAR in patients with gastric cancer (GC) who received curative treatment. PATIENTS AND METHODS: This study included 447 patients who underwent curative treatment for GC between 2013 and 2017. The prognosis and clinicopathological parameters were compared between patients with high and low CPARs. RESULTS: Overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a pretreatment CPAR of 5.0. Significant differences were observed in the 3- and 5-year OS rates of the CPAR-low (CPAR <5.0) and CPAR-high (CPAR ≥5.0) groups. The 3- and 5-year OS rates were 92.6% and 87.8%, respectively, in the CPAR-low group and 88.0% and 75.4% in the CPAR-high group. The CPAR was determined to be a significant prognostic factor for OS in a multivariate analysis (p=0.032). Similar results were observed for recurrence-free survival. CONCLUSION: The CAPR is a prognostic factor for GC patients. Therefore, the CAPR may be a promising nutritional biomarker of inflammation that can be applied in the management of GC patients.

DOI： 10.21873/anticanres.16719

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BACKGROUND/AIM: Intraoperative blood loss (IBL) has been reported to decrease survival after surgical resection of some malignancies; however, there are few reports on the effects of IBL on recurrence and survival in locally advanced esophageal cancer. Therefore, we investigated the relationship between IBL and postoperative recurrence and overall survival in patients who underwent surgery for esophageal cancer. PATIENTS AND METHODS: One hundred and ninety-eight patients with locally advanced esophageal cancer who underwent preoperative adjuvant chemotherapy and curative resection as standard treatment were included in this study. Based on a defined cut-off value for IBL, 27 and 171 patients were classified into the high and low IBL groups, respectively. The relationship between each group and clinicopathological factors, postoperative recurrence, and overall survival were investigated. RESULTS: In terms of the relationship between IBL and clinicopathological factors, the high IBL group had significantly more patients with pathological T4, longer operative time, and higher incidence of postoperative complications than the low IBL group. Both recurrence-free and overall survival were significantly worse in the high IBL group than in the low IBL group. Furthermore, multivariate analysis identified high IBL as an independent factor for predicting poor reference free survival and overall survival. CONCLUSION: Heavy IBL in patients with locally advanced esophageal cancer may be a useful predictor of postoperative recurrence and overall survival.

DOI： 10.21873/anticanres.16718

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AIM: Recently, change in the neutrophil to lymphocyte ratio (cNLR) has been shown to be a promising prognostic inflammation marker in some malignancies. The aim of the present study was to evaluate the clinical impact of the cNLR in gastric cancer patients who received curative gastrectomy. PATIENTS AND METHODS: The present study included 450 patients who underwent curative treatment for gastric cancer between 2013 and 2017 at Kanagawa Cancer Center. The cNLR was defined as follows: cNLR = NLR at 1 month after surgery-NLR at 1 week before surgery. The prognosis and clinicopathological parameters of the increased cNLR and decreased cNLR groups were analyzed. RESULTS: The OS stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a cutoff value of cNLR at 0.762. When comparing the patient background factors between the increased cNLR (≥ 0.762) and decreased cNLR (< 0.762) groups, there were no significant differences in age, sex, T status, or N status. In the increased cNLR group, the OS rates at 3 and 5 years after surgery were 87.5% and 77.3%, respectively, while those in the decreased cNLR group were 92.8% and 87.3%, which amounted to a statistically significant difference (p = 0.041). The univariate and multivariate analyses of factors associated with OS showed that cNLR was a significant prognostic factor. When the postoperative course was compared between the two groups, the incidence rates of postoperative surgical complications and other-cause death were significantly higher in the increased cNLR group (p = 0.001 and p = 0.005, respectively). CONCLUSION: The cNLR is one of the significant risk factors in gastric cancer patients. Our results suggested that the changes of inflammation status during perioperative periods might be a promising prognostic factor for gastrointestinal cancer patients.

DOI： 10.1007/s12029-023-00976-7

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BACKGROUND: Recently, change in the C-reactive protein/albumin ratio (CAR) has become a promising prognostic marker in some malignancies. The aim of the present study was to evaluate the clinical impact of change in the CAR in gastric cancer patients who received curative resection. METHOD: The present study included 458 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The prognosis and clinicopathological parameters were compared between patients who showed a high-change in CAR and those who showed a low-change in CAR. RESULTS: The OS stratified by each clinical factor was compared using a log-rank test, and a significant difference was observed using a 0.05 change in CAR. When the patient background factors were compared between the high-change (change in CAR ≥ 0.05) and low-change (change in CAR < 0.05) groups, the median age, sex ratio, T factor, and N factor were similar. In the low-change group, the OS rates at 3 and 5 years after surgery were 94.1% and 87.6%, respectively, which amounted to a significant difference from the low-change group, with rates of 83.6 and 77.5% in the high-change group. In the low-change group, the RFS rates at 3 and 5 years after surgery were 90.1% and 85.1%, respectively, while those in the high-change group 77.6 and 75.2%. The univariate and multivariate analyses of factors associated with OS and RFS showed that the change in CAR was a significant prognostic factor. CONCLUSIONS: The change in CAR is a significant risk factor and promising prognostic factor for gastric cancer patients.

DOI： 10.1007/s12029-023-00970-z

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The patient was a 27-year-old man. He was referred to our hospital because he was aware of a mass in his abdomen. An abdominal ultrasound showed a 70-mm mass lesion. Enhanced computed tomography showed a 70-mm mass with well- defined margins and heterogeneous internal enhancement near the proximal jejunum. The patient was diagnosed with a suspected primary submucosal tumor of the duodenum or small intestine, and surgery was planned to diagnose and treat the tumor. The tumor was located in the upper jejunal mesentery, and tumor resection and partial small bowel resection were performed. Histopathological examination revealed proliferation of spindle-shaped cells without karyomitosis, and mixed collagen fibers in the tissue. Immunohistochemistry showed β-catenin(+), SMA(+), AE1/AE3(-), KIT(-), CD34(-), and S-100(-). Based on these findings, we diagnosed primary desmoid fibromatosis of the small intestinal mesentery. In this report, we describe a case of primary desmoid fibromatosis of the small intestinal mesentery with a review of the literature.

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Perioperative adjuvant treatment and complete resection is the standard treatment for resectable pancreatic cancer and systemic chemotherapy is standard treatment for unresectable pancreatic cancer. To improve the survival of patients with pancreatic cancer, it is necessary to identify promising biomarkers to optimize the treatment. The availability of biomarkers may allow patients to receive a more aggressive or less toxic treatment. Recent studies showed that the inflammatory and nutritional status perioperatively and/or during chemotherapy affect short and long-term oncological outcomes in pancreatic cancer. Introduction of inflammatory and nutritional status evaluation in pancreatic cancer treatment might improve the postoperative surgical complications or chemotherapy-induced adverse events. However, to introduce these various nutritional and inflammation assessment tools in daily clinical practice, it is necessary to understand the characteristics of each nutrition and inflammation assessment tool. This review summarizes the background, current status, and future perspectives of nutrition and inflammation assessment tools in pancreatic cancer treatment.

DOI： 10.21873/anticanres.16572

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Language：English   Publisher：(一社)日本癌学会  

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BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

DOI： 10.21873/anticanres.16480

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BACKGROUND/AIM: To determine the clinical significance of pre-treatment circumferential tumor location within the esophageal wall in patients with locally advanced esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients (n=96) with cStage IB-III esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy were categorized into two groups based on the circumferential tumor location within the esophageal wall on diagnostic endoscopy: left or anterior wall group (L/A patients, n=49); right or posterior wall group (R/P patients, n=47). Analyses were conducted to examine the relationship between circumferential tumor location, clinicopathological characteristics, 3-year overall survival (3Y-OS), and 3-year recurrence-free survival (3Y-RFS). RESULTS: The lymph node status and recurrence rates of mediastinal lymph node metastases were significantly higher in patients with L/A than in patients with R/P. Furthermore, patients with L/A had significantly poorer 3Y-OS and 3Y-RFS than those with R/P. Tumor location within the esophageal wall was identified in multivariate analysis as an independent risk factor for 3Y-RFS (hazard ratio=2.92, 95% confidence interval=1.35-6.32, p=0.0064). CONCLUSION: Pre-treatment of circumferential tumor located within the esophageal wall may be a useful prognostic factor in patients with cStageIB-III esophageal squamous cell carcinoma who underwent curative resection after neoadjuvant chemotherapy.

DOI： 10.21873/anticanres.16436

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AIM: We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan PATIENTS AND METHODS: The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). RESULTS: A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). CONCLUSION: POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

DOI： 10.1007/s10147-023-02332-y

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BACKGROUND/AIM: Mucinous gastric carcinoma (MGC) has a poor prognosis. Due to the differences in clinicopathology factors between MGC and non-MGC (NMGC), it is difficult to compare them. In this study, we compared the clinicopathological characteristics and prognosis of MGC and NMGC patients. PATIENTS AND METHODS: For gastric carcinoma (GC), 3,042 gastrectomy patients were included in the study and divided into the MGC (n=86) and NMGC (n=2,956) groups. The characteristics and prognoses of patients in both groups were compared before and after (both groups, n=86) propensity score matching. RESULTS: Significant differences were observed in the tumor location (upper) (MGC group: 28.0% vs. NMGC group: 24.7%, p=0.003), tumor diameter (median) [65 mm (8-200 mm) vs. 40 mm (2-75 mm), p<0.001], lymph node metastasis (70.9% vs. 37.3%, p<0.001), venous invasion (57.0% vs. 40.4%, p<0.001), and lymphatic invasion (62.8% vs. 34.9%, p<0.001) before propensity score matching. The 5-year overall survival (OS) (70.9% vs. 76.2%, p=0.006) and cancer-specific survival (CSS) (75.5% vs. 82.4%, p=0.014) rates were significantly lower in the MGC group. After propensity score matching, there were no significant differences in either the 5-year OS (70.9% vs. 73.7%, p=0.230) or CSS (75.5% vs. 75.7%, p=0.587) rates. In addition, no substantial difference was observed in either of the recurrence forms. CONCLUSION: MGC is rare and usually diagnosed at a more advanced stage. However, MGC and NMGC have similar prognoses.

DOI： 10.21873/anticanres.16456

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Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR's clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.

DOI： 10.3390/jpm13060923

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The standard treatment for gastrointestinal cancer is surgical resection and perioperative adjuvant treatment. Thus far, gastrointestinal cancer research has mainly focused on cancer cells themselves. Recently, the tumor microenvironment (TME) has been a subject of investigation. The TME is a complex system composed of various cell types, including tumor cells, endothelial cells, stromal cells, immune cells, and extracellular components. Among them, the stromal cells surrounding tumor cells are being investigated in gastrointestinal cancers. Stromal cells play a role in tumor growth, invasion, and metastasis. Moreover, stromal cells are associated with increased chemotherapy resistance and reduced chemotherapy delivery. Therefore, it is necessary to develop prognostic or predictive factors that consider the tumor-stroma interaction. The tumor stroma ratio (TSR) has recently been shown to be a promising outcome prediction tool in various malignancies. The TSR is based on the proportion of the stroma to tumor area. Recent studies demonstrated that a high amount of stroma or low TSR was associated with a poor prognosis and was a predictor of various treatment modalities. Therefore, to optimize the gastrointestinal cancer treatment, it is necessary to understand the role of the TSR in gastrointestinal cancers. This review summarizes the background, current status, and future perspectives of the TSR for gastrointestinal cancer treatment.

DOI： 10.21873/anticanres.16346

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BACKGROUND: Peritoneal lavage cytology positivity (CY1) has been identified as a prognostic factor for distant metastases that is equivalent to peritoneal dissemination in Japan. Peritoneal lavage cytology is usually diagnosed by microscopic findings; a diagnostic procedure using a liquid biopsy (LB) technique has not yet been established. PATIENTS AND METHODS: We evaluated the feasibility of a LB approach using peritoneal lavage samples from 15 patients with gastric cancer. Samples were collected from both the Douglas pouch and the left subdiaphragmatic area, and cell-free DNA was extracted for analysis of TP53 mutations using droplet digital polymerase chain reaction. RESULTS: All 10 patients with CY1 had positive cytology for the left subdiaphragmatic specimen. However, only six out of the 10 patients had positive cytology for their Douglas pouch specimens, and these six patients had peritoneal tumor DNA (ptDNA) in these specimens. In all five patients with CY0, ptDNA was not detected. The overall survival was significantly shorter in the ptDNA-positive group than in the ptDNA-negative group. The survival of the group with a high amount of DNA from free intraperitoneal cells (ficDNA) was significantly worse than that of those with a low amount. In contrast, the group with a high amount of DNA from peritoneal cell-free DNA (pcfDNA) had significantly better survival than the group with a low amount. CONCLUSION: LB cytology showed equivalent utility to that of conventional microscopic examinations regarding its diagnostic ability. Therefore ptDNA, pcfDNA and ifcDNA are expected to be useful as prognostic factors.

DOI： 10.21873/anticanres.16367

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BACKGROUND/AIM: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC). PATIENTS AND METHODS: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined. RESULTS: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival. CONCLUSION: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC.

DOI： 10.21873/anticanres.16376

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BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is an anticancer-agent that is administered as third-line or later chemotherapy for metastatic gastric/gastroesophageal junction cancer (mGC/GEJC). Although inflammatory and nutritional statuses have attracted attention as prognostic factors for patients with mGC/GEJC in this therapy, their usefulness has not been fully clarified. Thus, this study investigated the clinical significance of prognostic nutritional index (PNI), neutrophil/lymphocyte ratio (NLR), and NLR/serum albumin (Alb) ratio in patients administered FTD/TPI. PATIENTS AND METHODS: This retrospective study included 64 patients who underwent FTD/TPI treatment for mGC/GEJC at Kanagawa Cancer Center, Kanagawa, Japan, between October 2019 and June 2022. Patients were divided into high and low PNI, NLR, and NLR/Alb groups according to their pretreatment blood data. This study evaluated the associations between the inflammatory and nutritional indexes and survivals. RESULTS: Overall survival (OS) and progression-free survival (PFS) of patients with low PNI were significantly poorer than those with high PNI. However, low PNI was not an independent prognostic factor for OS and PFS. There was no significant association between NLR and OS or PFS. In contrast, the OS of patients with high NLR/Alb was significantly poorer than those with high PNI and low NLR/Alb. Furthermore, multivariate analysis showed that high NLR/Alb was an independent prognostic factor for OS. CONCLUSION: The NLR/Alb may be a useful prognostic factor in patients with mGC/GEJC being administered FTD/TPI as third-line or later chemotherapy.

DOI： 10.21873/anticanres.16321

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BACKGROUND/AIM: Pancreatic cancer has the highest risk of venous thromboembolism (VTE). Additionally, chemotherapy for cancer patients increases the risk of developing VTE. Due to recent advances in neoadjuvant chemotherapy (NAC) regimens, more patients with resectable pancreatic cancer will receive NAC. However, the incidence, risk, and predictors of developing VTE in these patients have not been fully evaluated. PATIENTS AND METHODS: We retrospectively evaluated the incidence, risk, and predictors of VTE among 67 consecutive patients with resectable pancreatic cancer who received neoadjuvant combination therapy with gemcitabine+S-1 (NAC-GS) followed by surgery and 45 patients with resectable pancreatic cancer who underwent upfront surgery (Up-S). RESULTS: The incidence of VTE in the NAC-GS and Up-S groups was 10.4% and 6.6%, respectively. Preoperative D-dimer levels were significantly higher in the NAC-GS group, and D-dimer levels were significantly increased during NAC-GS. Preoperative D-dimer level was the only predictor for VTE in patients with resectable pancreatic cancer who received NAC-GS. CONCLUSION: There is an increased risk of developing VTE during NAC. Screening with D-dimer and taking appropriate measures to suppress critical VTE is essential to provide NAC to patients with resectable pancreatic cancer.

DOI： 10.21873/anticanres.16327

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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We present a case of benign esophageal leiomyoma with video-assisted thoracic enucleation. A 39-year-old woman was found to have an abnormal shadow in the mediastinum on a chest X-ray on a medical check-up. Chest CT performed for the purpose of close examination revealed a tumor with a size of 62×33 mm from the middle intrathoracic esophagus to the lower esophagus. Upper gastrointestinal endoscopy revealed a left half-circumferential elastic soft submucosal bulge in the thoracic middle-lower esophagus. Endoscopic ultrasonographic fine-needle aspiration biopsy(EUS-FNA)was performed, and immunostaining showed positive muscular markers SMA, but negative for CD34, c-kit, and S-100, and the diagnosis was esophageal leiomyoma. Therefore, thoracoscopic-assisted esophageal leiomyoma resection was performed. Postoperative immunohistological examination showed positive for SMA and Desmin, and the diagnosis was leiomyoma.

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BACKGROUND/AIM: The present study quantified the changes in the dietary and nutritional intake after gastrectomy between elderly and non-elderly patients. PATIENTS AND METHODS: This prospective observational study enrolled patients who underwent curative gastrectomy for gastric cancer. RESULTS: Twenty-three patients ≥ 75 years old were classified into the elderly group, and 127 patients < 75 years old were classified into the non-elderly group. The respective median % dietary intake losses at 1 and 3 months postoperatively were -12.4% and -5.3% in the elderly group and -8.3% and -2.8% in the non-elderly group (p = 0.075 and 0.080). On comparing the intake loss of three major nutrients, the respective median % lipid intake losses at 1 and 3 months postoperatively were -13.5% and -5.8% in the elderly group and -7.3% and 0% in the non-elderly group (p = 0.029 and 0.045). CONCLUSION: Our results suggested that elderly patients experienced more serious lipid intake loss after gastrectomy than non-elderly patients.

DOI： 10.1007/s12029-021-00776-x

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BACKGROUND: We investigated the clinical influence of the prealbumin level on the gastric cancer survival and recurrence after curative treatment. METHODS: This study included 447 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A prealbumin level of 20 mg/dl was regarded as the optimal point of classification, considering the 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 80.7% and 65.0% in the low-prealbumin group, respectively, and 93.1% and 87.9% in the high-prealbumin group, respectively, a statistically significant difference (p < 0.001). The RFS rates at 3 and 5 years after surgery were 71.7% and 68.0% in the low-prealbumin group, respectively, and 90.1% and 84.7% in the high-prealbumin group, respectively, a statistically significant difference (p = 0.031). A multivariate analysis demonstrated that the prealbumin level was a significant independent risk factor for the OS and RFS. In addition, the rate of introduction of adjuvant chemotherapy was significantly lower and the frequency of peritoneal recurrence and lymph node recurrence significantly higher in the low-prealbumin group than in the high-prealbumin group. CONCLUSION: Prealbumin is a risk factor for the survival in patients who undergo curative treatment for gastric cancer. It is necessary to develop an effective plan of perioperative care and surgical strategy according to the prealbumin level.

DOI： 10.1007/s12029-021-00777-w

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Preoperative inflammatory and nutritional statuses have potential prognostic effects on patients with gastric cancer (GC) after curative gastrectomy. We investigated the prognostic usefulness of the preoperative neutrophil-to-lymphocyte ratio/albumin ratio (NLR/Alb) in patients with GC. Among 483 patients who underwent gastrectomy for GC, the preoperative prognostic nutritional index (PNI), NLR, and NLR/Alb were calculated using preoperative blood test data. The patients were divided into the high and low PNI, NLR, and NLR/Alb groups. The associations of preoperative PNI, NLR, and NLR/Alb with clinicopathological features, 3-year (3Y) overall survival (OS) rates, and relapse-free survival (RFS) rates after gastrectomy for GC were evaluated. The number of female individuals and the C-reactive protein levels were significantly higher in the high- compared to the low-NLR/Alb group (both p < 0.05). The 3Y OS and 3Y RFS rates following gastrectomy were significantly lower in the high- compared to the low-NLR/Alb group (88.2% vs. 97.8%, p = 0.003 and 84.2% vs. 95.6%, p = 0.002, respectively). In multivariate analysis, high NLR/Alb could independently predict prognosis and recurrence (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.26-13.55; p = 0.02 and HR: 3.16; 95% CI: 1.34-7.45, p = 0.009, respectively). Preoperative NLR/Alb might be a useful prognostic factor for patients with GC after curative gastrectomy.

DOI： 10.3390/jpm13030432

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BACKGROUND/AIM: Patients are at-risk for vitamin B12 deficiency after total gastrectomy due to a lack of intrinsic factors. The aim of the study was to clarify the clinical course and risk factors for vitamin B12 deficiency after total gastrectomy for gastric cancer patients. PATIENTS AND METHODS: Patients who underwent curative resection for gastric cancer were selected from the medical records of the Yokohama City University from 2000 to 2020. A logistic regression analysis was performed to identify risk factors for vitamin B12 deficiency. RESULTS: We evaluated 47 patients. The median serum vitamin B12 levels before surgery were 359 pg/ml, while those at 3, 6, 9, and 12 months after surgery these were 255 pg/ml, 197.5 pg/ml, 195 pg/ml, and 206 pg/ml, respectively. Univariate analyses to identify factors associated with vitamin B12 deficiency at 6 months after surgery showed that the occurrence of postoperative complications was a significant risk factor (OR=6.347, 95%CI=1.607-25.774, p=0.009), while adjuvant chemotherapy was a marginally significantly risk factor (OR=3.562, 95%CI=0.877-14.477, p=0.076). CONCLUSION: Almost half of the patients were diagnosed with vitamin B12 deficiency at 6 months after total gastrectomy for gastric cancer. In addition, the occurrence of postoperative complications and adjuvant chemotherapy were risk factors for vitamin B12 deficiency at 6 months after surgery.

DOI： 10.21873/anticanres.16207

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BACKGROUND: No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy. METHODS: We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups. RESULTS: The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03). CONCLUSIONS: Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.

DOI： 10.1016/j.ejso.2022.09.003

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BACKGROUND/AIM: When nivolumab is administered as second-line therapy for esophageal cancer, radiotherapy may also be provided in cases either concurrently or sequentially. The aim of this study was to retrospectively examine whether the incidence of adverse events increases in such cases. PATIENTS AND METHODS: Twenty-two esophageal cancer patients [17 males and 5 females; mean age 71 years (range=58-87 years)] treated with nivolumab were included. Patients were divided into two treatment groups: nivolumab alone (N group) (12 patients) and nivolumab combined with radiotherapy (R group) (10 patients). All patients had squamous cell carcinoma. The primary outcomes measured were the severity and frequency of adverse events. RESULTS: Adverse events were seen in 6 of the 12 patients in the N group and 8 of the 10 in the R group. There were significantly more adverse events in the R group (p=0.035), but no difference in Grade 3 or higher adverse events (p=0.781), indicating that the adverse events were controllable. There was no significant difference in treatment effect between the N and R groups. CONCLUSION: In this report, 50% of adverse events in the N group were grade 3-4, 25% of which were grade 4, as seen in previous reports. In the present study, the side effects were not enhanced by treatment with immune checkpoint inhibitors plus radiotherapy. Immune checkpoint inhibitors plus radiation therapy would be a relatively safe treatment and may become an option for esophageal cancer treatment in the future.

DOI： 10.21873/invivo.13264

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BACKGROUND/AIM: Gastrectomy with lymphadenectomy is a standard treatment for gastric cancer. Anastomotic leakage remains a potentially fatal complication of gastrectomy. Forceful stapler extraction may cause anastomotic complications. We focused on the duodenal peristalsis, as we hypothesized that it might cause forceful stapler extraction. We then retrospectively investigated duodenal peristalsis and reviewed videos of Da Vinci system cases to clarify the relationship between peristalsis and anastomotic complications. PATIENTS AND METHODS: Forty-nine cases with stored videos of laparoscopic surgery using the Da Vinci system from 2015 to March 2021 were included. Peristalsis was defined by repeated contraction and expansion that was clearly visible three or more times in a row. The duodenum was investigated because it is frequently observed during gastrectomy. Suture failure was evaluated in cases with and without peristalsis. RESULTS: The study population included 49 patients [male, n=32; female, n=17; median age, 71 (42-82) years]. Duodenal peristalsis was observed in 14 (28.6%) cases. Three patients experienced complications. A comparative study of cases with and without complications showed significant peristalsis in cases with complications (p=0.0198). CONCLUSION: A new definition to evaluate duodenal peristalsis was established. Anastomotic complications were significantly more frequent in cases with peristalsis (p=0.0198). Our results suggest the utility of manual over-sewing or the use of reinforcement material.

DOI： 10.21873/invivo.13281

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BACKGROUND/AIM: We investigated the influence of the preoperative Oral Health Assessment Tool (OHAT) score on the outcomes of patients with esophageal cancer after curative surgery. PATIENTS AND METHODS: This study included 90 patients with esophageal cancer who underwent curative surgery and who were screened with the OHAT between 2008 and 2021. The OHAT consists of eight categories with three possible scores. The risk factors for 5-year overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Patients were divided into healthy (n=42) and unhealthy (n=48) groups. The OHAT score was identified as a significant risk factor for postoperative pneumonia (11.9% vs. 43.8%, p=0.001) and postoperative hospital stay (20.5 days vs. 50.1 days, p=0.042). The 5-year OS rate after surgery was 71.2% in the healthy group and 43.2% in the unhealthy group, which was a significant difference (p=0.015). A multivariate analysis showed that a high OHAT score was a significant independent factor for 5-year OS (p=0.034). CONCLUSION: The OHAT score was a useful prognostic marker in patients who underwent curative surgery for esophageal cancer. To improve the oncological outcomes of patients with esophageal cancer, it is necessary to carefully plan perioperative oral/dental care using the OHAT score.

DOI： 10.21873/invivo.13327

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BACKGROUND/AIM: The platelet-to-lymphocyte ratio (PLR) is a promising prognostic marker in some malignancies. The present study evaluated the clinical impact of the PLR in patients with gastric cancer who underwent curative resection. PATIENTS AND METHODS: This study included 258 patients who underwent curative treatment for gastric cancer between 2005 and 2020. The prognosis and clinicopathological parameters between the high- and low-PLR statuses were analyzed. RESULTS: The overall survival (OS) stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a pretreatment PLR of 150. When comparing the patient backgrounds between the high-PLR (PLR≥150) and low-PLR (PLR<150) groups, there were no significant differences between the two groups. The OS rates at 3 and 5 years after surgery were significantly higher at 70.8% and 60.4%, respectively, for the high-PLR group than at 83.6% and 79.7%, respectively, for the low-PLR group. Univariate and multivariate analyses of the OS showed that the PLR was a significant prognostic factor. In addition, when comparing the first recurrence sites, there were significant differences in peritoneal recurrence. CONCLUSION: The PLR is a significant risk factor for gastric cancer, making it a promising prognostic factor for patients with gastric cancer.

DOI： 10.21873/invivo.13379

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BACKGROUND: We investigated the impact of the lymphocyte-to-C-reactive protein ratio (LCR) on esophageal cancer survival and recurrence after curative treatment. PATIENTS AND METHODS: This study included 89 patients who underwent curative surgery followed by adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: LCR of 12,177 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 33.2% and 29.9% in the LCR low group, respectively, and 74.0% and 60.9% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). The RFS rates at 3 and 5 years after surgery were 25.3% and 21.7% in the LCR low group, respectively, and 52.1% and 47.4% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). A multivariate analysis demonstrated that the LCR was a significant independent risk factor for both the OS and RFS. CONCLUSION: LCR was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the LCR.

DOI： 10.4103/jcrt.jcrt_139_21

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BACKGROUND/AIM: The prognostic nutritional index (PNI) has been reported as an immunonutritional index that can easily evaluate nutritional status and immunocompetence from blood tests. The purpose of this study was to investigate the usefulness of PNI as a prognostic factor in postoperative gastric cancer patients. PATIENTS AND METHODS: In this retrospective cohort study, we evaluated 258 patients with pStage I-III gastric cancer who underwent radical resection at Yokohama City University Hospital, from 2015 to 2021. To examine the association with prognosis, we analyzed clinicopathological factors including PNI (<47/≥47), age (<75/≥75), sex (male/female), depth (pT1/≥pT2), lymph node metastasis (pN+/pN-), lymphatic invasion (ly+/ly-), vascular invasion (v+/v-), histological type (enteric/spread) and postoperative complications. RESULTS: In univariate analysis, PNI (p<0.001), depth of tumor invasion (p<0.001), lymph node involvement (p<0.001), age (p=0.002), lymphatic invasion (p<0.001), vascular invasion (p<0.001), and postoperative complications (p=0.003) were associated with overall survival. In multivariate analysis, PNI (HR=2.100, 95% confidence interval 1.225-3.601, p=0.007), tumor invasion, lymph node metastasis, and postoperative complications were shown as poor prognostic factors for overall survival. CONCLUSION: PNI is an independent prognostic factor for overall and recurrence-free survival in postoperative gastric cancer patients. PNI could be implemented in clinical practice to identify patients at higher risk for poor outcomes.

DOI： 10.21873/invivo.13207

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Multidisciplinary treatment for esophageal cancer leads to nutritional and inflammatory changes. Recent studies showed that nutritional and inflammatory changes during multidisciplinary treatment affect both short and long-term oncological outcomes in esophageal cancer treatment. Therefore, evaluation of the nutritional and inflammatory status during treatment is necessary in order to optimize and utilize multidisciplinary therapy for esophageal cancer. If patients with esophageal cancer are able to determine their nutritional and inflammatory status, they will be able to select the optimal esophageal cancer, anti-inflammation, and nutritional treatments. Various types of nutrition and inflammation assessment tools have been developed and reported for esophageal cancer, with each tool having its own clinical characteristics, which must be understood before being applied in clinical practice. This review summarizes the background, current status, and future perspectives on the application of nutrition and inflammation assessment tools in esophageal cancer treatment.

DOI： 10.21873/invivo.13051

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BACKGROUND/AIM: Clinical staging in the eighth edition of the Union for International Cancer Control TNM classification (TNM8) is reported to predict the prognosis of patients with gastric cancer. However, there have been no reports on using the TNM8 for prognostic stratification of patients with adenocarcinoma of the esophagogastric junction (AEG). This study aimed to investigate whether it was possible to stratify the prognosis of patients who underwent curative surgery for Siewert type II/III AEG according to the TNM8 clinical stage (cStage). PATIENTS AND METHODS: This study included patients with Siewert type II/III AEG who underwent curative surgery between 2000 and 2019 at Kanagawa Cancer Center. Those who received neoadjuvant chemotherapy were excluded. We investigated the survival of patients with AEG of each TNM8 cStage. RESULTS: This study included 138 patients, among whom 102 (74%) had Siewert type II and 36 (26%) had Siewert type III AEG. A total of 50, 38, 43, and seven patients were classified with cStage I, II, III, and IV, respectively. The median duration of follow-up of the survivors was 54.7 months. The 5-year overall survival rate of the entire cohort was 65.8%, whereas for patients with cStage I, II, III and IV was 81.6%, 69.0%, 54.3% and 14.3%, respectively. The hazard ratio with reference to cStage I was 1.83, 3.07, and 8.13 for cStage I, III, and IV, respectively, increasing in a stepwise manner. CONCLUSION: TNM8 Clinical staging is able to stratify the prognosis of patients with Siewert type II/III AEG.

DOI： 10.21873/invivo.13268

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AIMS: Feeding jejunostomy tube (FJT) is one option for enteral nutrition after pancreaticoduodenectomy (PD); however, controversy regarding its clinical outcome(s) persists. The aim of the present study was to determine the safety and efficacy of FJT management. MATERIALS AND METHODS: Data from 156 consecutive patients, who underwent PD between January 2015 and December 2017, were retrospectively reviewed. Safety was assessed according to postoperative and tube-related complications. Nutritional efficacy was evaluated based on improvement in serum albumin levels. RESULTS: Thirty-day morbidity and mortality rates were 61.0% (n = 95) and 1.9% (n = 3), respectively. The rates of clinically relevant postoperative pancreatic fistula and delayed gastric emptying were 30.8% and 9.0%, respectively. In total, nine (5.8%) patients experienced complications directly related to FJT. Eight patients experienced surgical site infection adjacent to the catheter/skin interface. Although all required catheter removal at the bedside or in the office, none required reoperation. The improvement in serum albumin level 1 month after PD was 40.7% compared with 1 week after PD. CONCLUSION: FJT was useful in improving nutritional intake and status. Although FJT was associated with minor self-limiting complications, they could be managed by simple bedside or office treatment. As such, results of this study support the safety and efficacy of the FJT protocol used in the authors' department for nutritional management.

DOI： 10.4103/jcrt.JCRT_1655_20

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BACKGROUND/AIM: SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection. PATIENTS AND METHODS: We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival. RESULTS: SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002). CONCLUSION: SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection.

DOI： 10.21873/anticanres.16097

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Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

DOI： 10.1007/s00535-022-01919-y

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BACKGROUND/AIM: The present study evaluated the clinical impact of other metachronous or synchronous primary cancer (OPC) in patients who received curative treatment for esophageal cancer. PATIENTS AND METHODS: The present study included 168 patients who underwent curative treatment for esophageal cancer between 2005 and 2018. Prognosis and differences between the OPC status (metachronous/synchronous) and clinic pathological parameters was analyzed. RESULTS: A total of 168 patients were included in this study. Forty patients were diagnosed with metachronous/synchronous OPC. When comparing the clinicopathological factors between the patients with and without OPC, the patients' background and postoperative clinical courses were very similar between the two groups. The 3- and 5-year overall survival rates in patients with esophageal cancer with OPC were 66.0% and 54.5%, respectively, while those in patients without OPC were 50.1% and 41.4%, respectively. There was no statistically significant difference in these rates (p=0.156). The OPC status was not included in the final multivariate analysis model. CONCLUSION: The OPC status was not found to be a prognostic factor for patients who received curative treatment for esophageal cancer. Therefore, it is not necessary to avoid performing curative treatment for esophageal cancer because of a patient's OPC status.

DOI： 10.21873/anticanres.16072

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The standard treatment for gastric cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastric cancer leads to nutritional and inflammatory changes. Nutritional and inflammatory changes during multidisciplinary treatment can lead to poor physical activity, severe toxicity in patients receiving chemotherapy or radiation therapy, and poor oncological outcomes. Evaluation of the perioperative nutritional and inflammatory status during treatment is necessary in order to utilize and optimize multidisciplinary therapy for gastric cancer. If physicians were able to detect the perioperative nutritional and inflammatory status before and during gastric cancer treatment, they would be able to select the optimal treatment and perioperative nutritional treatment. Recently, various types of nutrition and inflammation assessment tools were developed and reported for gastric cancer. These nutrition and inflammation assessment tools have some clinical advantages, such as ease of implementation, perioperative accessibility, and low cost. On the other hand, each tool has its own clinical characteristics, which must be understood before using it in the clinical practice. This review summarizes the background, current status, and future perspectives on the application of nutrition and inflammation assessment tools in gastric cancer treatment.

DOI： 10.21873/anticanres.16023

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Language：Japanese   Publishing type：Research paper (scientific journal)  

According to the risk classification of recurrence, the standard treatment for gastrointestinal stromal tumor(GIST)is complete surgical resection and postoperative adjuvant therapy with imatinib; however, the usefulness of neoadjuvant therapy is unclear. We report a case of giant GIST in the pelvis suspectedly having bladder infiltration that was radically resected and underwent preoperative imatinib therapy. A 52-year-old man visited a clinic because of abdominal pain, fever, and frequent urination. An abdominal mass was determined, and the patient was referred to our hospital for detailed examination and treatment. Contrast-enhanced CT revealed a 17 cm diameter irregular mass from the lower navel to the pelvis, and the bladder boundary was partially unclear. Transrectal biopsy was performed using endoscopic ultrasonography, and according to the Fletcher classification, a high-risk GIST was diagnosed. After preoperative imatinib therapy of 400 mg/day was administered for 3 months, surgery was performed. The tumor was strongly adhered to the bladder, but no invasion was observed, and partial small intestine resection was performed. The surgical margin was negative without capsule damage. On day 34 postoperatively, imatinib therapy was resumed, and as of 1 year postoperatively, the course is well without recurrence.

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A 74-year-old man presented with a metastatic brain tumor in the right parietal lobe observed through an MRI scan. Lower gastrointestinal endoscopy revealed that the tumor was located in the rectum. He was diagnosed with Stage Ⅳb rectal cancer(cT4aN1bM1b[BRA, SKN]). After prior stereotactic radiotherapy for brain metastases, the patient underwent rectal amputation and D3 dissection as management for the primary tumor. His postoperative course was uneventful, and he was discharged from the hospital 33 days postoperatively. He displayed partial response with capecitabine plus L-OHP therapy, and chemotherapy was terminated due to the development of renal dysfunction. On follow-up, elevated tumor markers, enlarged left mediastinal lymph nodes, and FDG accumulation on PET-CT were observed. Despite initiating UFT/UZEL therapy, the patient was judged to have progressive disease. The patient was then administered 5-FU plus l-LV plus CPT-11. However, this was later discontinued due to the development of hyperammonemia. The patient was placed on follow-up observation due to the decrease in his tumor markers and the disappearance of his enlarged lymph nodes. He is still alive seven years after his initial diagnosis. We report a case of a patient with rectal cancer that metastasized to the brain and the skin. He was successfully managed with multidisciplinary therapy. A relevant literature discussion is also included.

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: We sought to identify an optimal combination of survival risk stratification markers in patients with pathological (p) stage II/III gastric cancer (GC) after curative resection. METHODS: We measured the expression levels of 127 genes in pStage II/III GC tissues of two patient cohorts by quantitative polymerase chain reaction (qPCR) and the expression of 1756 proteins between two prognosis (good and poor) groups by proteomic analysis to identify candidate survival stratification markers. Further, immunohistochemistry (IHC) using tumor microarrays (TMAs) in another cohort of patients was performed to identify an optimal biomarker combination for survival stratification in GC patients. RESULTS: secreted protein acidic and rich in cysteine (SPARC), erb-b2 receptor tyrosine kinase 2 (ERBB2), inhibin subunit beta A (INHBA), matrix metallopeptidase-11 (MMP11), tumor protein p53 (TP53), and platelet-derived growth factor receptor-beta (PDGFRB) were identified as candidate biomarkers from qPCR analysis, and SPARC and galectin-10 were obtained from the proteomic analysis. The combination of PDGFRB, INHBA, MMP11, and galectin-10 was identified as the optimal combination of survival risk stratification markers. CONCLUSIONS: A combination of four proteins in GC tissues may serve as useful survival risk stratification markers in patients with pStage II/III GC following curative resection. Our results may facilitate future multicenter prospective clinical trials.

DOI： 10.3390/cancers14184427

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BACKGROUND/AIM: Preoperative sarcopenia is associated with various cancers and affects the long-term prognosis of patients. After gastrectomy for gastric cancer, dynamic changes in body composition occur, and sarcopenia becomes more apparent after surgery than before surgery. However, the relationship between sarcopenia in the early postoperative period and long-term survival is not fully understood. The aim of this study was to determine the effects of surgical sarcopenia on long-term outcomes of patents with gastric cancer. PATIENTS AND METHODS: We included 408 patients who underwent curative gastrectomy (distal or total gastrectomy) for gastric cancer at the Kanagawa Cancer Center from December 2013 to November 2017. Sarcopenia was defined using the skeletal muscle index (SMI), using computed tomography (CT) one month after gastrectomy. We compared the long-term outcomes between patients with and without sarcopenia. RESULTS: The 5-year overall survival (OS) rates were 83.2% and 91.4% in the surgical and non-surgical sarcopenia groups, respectively. The hazard ratio (HR) of surgical sarcopenia for OS was 2.410 (95% confidence interval (CI)=1.321-4.396). In addition, surgical sarcopenia was associated with non-cancer-related deaths and deaths from other cancers. CONCLUSION: Patients with surgical sarcopenia after gastrectomy should be carefully monitored not only for gastric cancer recurrence but also for the occurrence of other diseases, including other cancers.

DOI： 10.21873/anticanres.15957

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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BACKGROUND/AIM: The albumin-bilirubin (ALBI) score is a promising tool for the evaluation of the perioperative hepatic function. The present study aimed to evaluate the clinical impact of the preoperative ALBI status in patients with gastric cancer (GC) who received curative treatment. PATIENTS AND METHODS: The present study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7849. The 3- and 5-year OS rates were 87.3% and 80.9%, respectively, in the ALBI-low group, and 66.9% and 60.6% in the ALBI-high group; these differences were statistically significant (p<0.001). The ALBI score was included in the final multivariate analysis model [Hazard ratio (HR)=2.120, 95% confidence interval (CI)=1.177-3.818, p=0.012]. Similar results were observed for RFS. In addition, the ALBI score correlated with the introduction of postoperative adjuvant chemotherapy. CONCLUSION: The preoperative ALBI score correlated with both the OS and RFS of GC patients as well as the clinical course of adjuvant chemotherapy. Taken together, the ALBI score is a promising prognostic factor for GC.

DOI： 10.21873/anticanres.15887

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BACKGROUND/AIM: This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 μg/day replacement compared with oral Vitamin B12 1,500 μg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive oral Vitamin B12 500 μg/day or Vitamin B12 1,500 μg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment. RESULTS: From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 μg/day arm and 38 to Vitamin B12 1,500 μg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level >200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 μg/day arm and 100% (38/38) in the Vitamin B12 1,500 μg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar. CONCLUSION: Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 μg/day replacement is as effective and safe as oral Vitamin B12 1,500 μg/day replacement for Vitamin B12 deficiency.

DOI： 10.21873/anticanres.15891

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BACKGROUND/AIM: Epiregulin (EREG) is a ligand of the epidermal growth factor receptor (EGFR) and promotes tumour progression mainly by stimulating the EGF pathway. We investigated the clinical significance of EREG mRNA expression in cancer tissues from patients with gastric cancer (GC) in pathological (p) Stage II/III who have undergone curative surgery. PATIENTS AND METHODS: Expression of EREG mRNA was measured in cancer tissues obtained from 253 patients with pStage II/III GC who underwent curative surgery. Patients were divided into groups based on high or low expression of EREG mRNA. We examined the relationship between EREG mRNA expression levels and clinicopathological features and survival. RESULTS: Clinicopathological features did not vary between the high and low EREG mRNA expression groups. Overall survival was significantly lower in the high-expression group compared to that in the low-expression group (5-year survival probability: 55.0% vs. 73.0%; p=0.005). Multivariate analysis showed EREG mRNA expression to be an independent predictor of poor survival (hazard ratio=1.794; 95% confidence interval=1.186-2.712; p=0.006). CONCLUSION: Expression of EREG mRNA in cancer tissue from patients with pStage II/III GC may be a useful prognostic marker after curative surgery.

DOI： 10.21873/anticanres.15880

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BACKGROUND: Glutaraldehyde (GA)-fixed autologous tissues, including the pericardium, are widely used as patches and valve substitutes in cardiovascular surgery. However, GA treatment causes tissue calcification. No rapid anticalcification method has been established for use during surgery. Here, we aimed to establish a rapid anticalcification method using ethanol, as has already been demonstrated for bioprosthetic valves. METHODS: Thoracic aorta tissues were first fixed with GA for 3 min and then treated with ethanol for 0 (group 2), 10 (group 3), 20 (group 4), and 30 (group 5) min; untreated tissues (group 1) served as the control. The treated tissues were subdermally implanted into 3-week-old male Wistar rats and kept in place for 28 days. The calcification in each explant was semiquantitatively evaluated by annotating and measuring the area using virtual slides, and the data obtained were statistically analyzed. RESULTS: Semiquantitative analysis revealed that calcification of the implants from the untreated group (group 1; P = 0.0014) and groups 4 (P = 0.0014) and 5 (P = 0.0031) was significantly lower than that of implants from group 2. Moreover, implants from group 3 showed a tendency toward decreased calcification, although it was not significant (P = 0.0503). CONCLUSIONS: A rapid ethanol treatment prevents calcification of GA-fixed tissues in a rat model of subdermal implantation. This method may facilitate effective and rapid anticalcification of autologous tissues for use during cardiovascular surgery.

DOI： 10.1186/s13019-022-01895-7

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BACKGROUND/AIM: Postoperative complications are associated with increased recurrence in colorectal cancer (CRC). We investigated the impact of infectious complications on the recurrence of CRC and overall survival after curative surgery in a single study group. PATIENTS AND METHODS: In total, 1,668 patients who underwent radical resection for CRC in Yokohama City University, Yokohama Minami Kyosai Hospital, and Kanagawa Cancer Center between 2011 and 2019 were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (Non-IC group). The risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: Postoperative complications were found in 560 of the 1,668 patients (33.5%), and IC, which occurred in 312 patients (18.7%), included pneumonia, anastomotic leakage, and intraperitoneal abscess. The 5-year OS rates in the Non-IC and IC groups were 95.5% and 90.4%, respectively, while the 5-year RFS rates were 74.4% and 68.1%, respectively. The multivariate analysis demonstrated that postoperative IC were significant independent risk factors for OS and RFS. CONCLUSION: The presence of postoperative IC after CRC resection is associated with decreased long-term survival. The surgical procedure, surgical strategy, and perioperative care should be carefully planned in order to avoid causing IC.

DOI： 10.21873/anticanres.15755

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BACKGROUND: The current expectancy of long-term survival of patients with pathological stage (pStage) III gastric cancer (GC) is not satisfactory. However, neoadjuvant chemotherapy (NAC) is expected to improve survival rates in these patients. An appropriate pretherapeutic diagnostic strategy is necessary for selecting patients who are eligible for NAC. Surgical findings can often identify serosal invasion or metastatic lymphadenopathy, thereby facilitating the selection of candidates for NAC. Therefore, we aimed to evaluate the accuracy and potential of surgical staging in improving the management and survival of patients with GC. PATIENTS AND METHODS: We assessed the accuracy of surgical staging in comparison to preoperative staging using data from patients who underwent gastrectomy for GC. In addition, differences in survival after using the surgical staging criterion were assessed. RESULTS: A total of 915 patients were evaluated in this study. The sensitivity of surgical staging in detecting pStage III in the surgical T4N0-3 plus surgical T3N1-3 group was satisfactory (79.3%). The proportion of patients with pStage I using the surgical staging criterion was 7.8%. CONCLUSION: Surgical staging using laparoscopy or laparotomy may assist in selecting candidates for enrollment in clinical trials for NAC.

DOI： 10.21873/anticanres.15750

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BACKGROUND/AIM: Perioperative systemic inflammation affects the long-term oncological outcomes in cases of malignancies. We evaluated the clinical impact of the preoperative systemic inflammation score (SIS) in resectable esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rate, we set the cut-off value for SIS at 2 in the preset study. Among the 168 total patients, 119 were categorized as the Low-SIS group, and 49 were categorized as the High-SIS group. The respective 3- and 5-year OS rates were 61.9% and 52.4% in the Low-SIS group and 33.3% and 26.6% in the High-SIS group. There were significant differences in OS (p<0.001). The SIS was therefore selected for the final multivariate analysis model (hazard ratio=2.094, 95% confidence interval=1.355-3.234, p<0.001). On comparing the perioperative clinical course between the High- and Low-SIS groups, there were significant differences in the rate of postoperative anastomosis leakage of grade ≥2 between the groups (61.5% in the High-SIS group vs. 30.3% in the Low-SIS group; p=0.021). CONCLUSION: The systemic inflammation score had a clinical effect on the long-term oncological outcomes in esophageal cancer patients, suggesting that it might be a promising prognostic factor for esophageal cancer patients.

DOI： 10.21873/anticanres.15749

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Basic and clinical reports have suggested that eicosapentaenoic acid (EPA) exhibits anti-tumor activity. The present study evaluated whether perioperative EPA could improve the survival of patients with localized gastric cancer as a key secondary endpoint of a randomized clinical study. The present study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA on body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either the standard-diet group (EPA-off group) or EPA-on group by a centralized dynamic method. An EPA-enriched supplement (ProSure®) was given to the EPA-on group in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. Among the 126 patients who were randomized, 123 patients (EPA-off group, n=60; EPA-on group, n=63) were examined in the survival analyses. All background factors were well balanced between the two groups. The 3-year and 5-year overall survival rates were 74.6 and 67.8%, respectively, in the EPA-off group, and 77.8 and 76.2% in the EPA-on group. There was no significant difference between the EPA-off and EPA-on groups (hazard ratio, 0.77; P=0.424). In the subgroup analysis, the hazard ratio was 0.39 in patients who received neoadjuvant chemotherapy and 0.57 in patients with nodal metastasis. In conclusion, a clear survival benefit of perioperative EPA was not observed in localized gastric cancer. The value of EPA should be further tested in a future study in patients with unfavorable advanced gastric cancer. Clinical trial number: UMIN000006380; date of registration, September 21, 2011.

DOI： 10.3892/ol.2022.13272

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

DOI： 10.1002/jso.26730

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BACKGROUND/AIM: To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC). PATIENTS AND METHODS: Patients with unresectable advanced GC and recurrence after curative resection who received nivolumab monotherapy were included in the study. Survival was compared between patients who did and did not develop irAEs, and between those who continued and discontinued treatment due to irAEs. RESULTS: Of 110 GC patients, 22 developed irAEs. Grade ≥3 IrAEs included rash and diarrhoea associated with enteritis. Progression-free and overall survival (OS) were significantly better in patients with irAEs than in those without. The overall survival of patients who continued treatment despite irAEs was better than that of those who discontinued treatment. CONCLUSION: irAE development was associated with better survival in patients with GC who received nivolumab monotherapy. Continuing nivolumab with appropriate treatment in GC patients with irAEs may improve survival.

DOI： 10.21873/anticanres.15626

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BACKGROUND: As non-ampullary duodenal cancer is relatively rare, the optimal treatment strategy, including the appropriate surgical procedure and efficacy of adjuvant chemotherapy, remains unclear. This nationwide survey aimed to clarify the actual lymph node spread pattern and determine the optimal treatment strategy for this disease, using a large-scale database. METHODS: We used a questionnaire and a retrospective registry of 1083 patients with non-ampullary duodenal cancer who had undergone surgery during 2008-2017 in 114 high-volume Japanese Society of Hepatobiliary and Pancreatic Surgery-certified training institutions. Propensity score-matched analyses were conducted to minimise background bias. Cox regression was performed to identify covariates associated with recurrence-free survival. There were distinct disparities in the nodal dissection rate according to the predominant tumor location and tumor invasion depth. Metastases were frequently observed in the peripancreatic nodes and those along the superior mesenteric artery, irrespective of tumor location. Their dissection seemed to be beneficial for improved survival. In the overall cohort, no survival benefit was observed in patients who received adjuvant chemotherapy when compared with that in patients who underwent surgery alone. Nevertheless, in the matched cohort, adjuvant chemotherapy for > 6 months was associated with a significant improvement in recurrence-free survival (median: 43.5 vs. 22.5 months, p = 0.016), particularly in patients with tumor invasion of the subserosa or deeper tumor invasion, lymph node metastasis, or elevated serum carbohydrate antigen 19-9 levels. CONCLUSION: Pancreatoduodenectomy should be the standard procedure for advanced non-ampullary duodenal cancer. Adjuvant chemotherapy for > 6 months, especially for advanced tumors, significantly improves survival.

DOI： 10.1007/s00535-021-01841-9

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PURPOSE: The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. METHODS: This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. RESULTS: PFS was superior in group M (median PFS; 8.7 vs. 11.5 months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0 months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6 weeks/course, P = 0.051) in the induction term. CONCLUSION: We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

DOI： 10.1007/s00384-021-04064-9

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Some authors have suggested that a relationship exists between gastrectomy for gastric cancer and metabolic bone disorders. However, few studies have investigated metabolic bone disorders after gastrectomy for gastric cancer in detail. Thus, we reviewed the findings of our recent prospective study and those of other reports on this subject. Osteoporosis and osteomalacia have been observed after gastrectomy and appear to be caused by reduced food intake and absorption, and steatorrhea. Moreover, the incidence of fracture is high after gastrectomy, although subtotal or total gastrectomy and reconstruction for gastric cancer have not been identified as significant risk factors for decreased bone mineral density (BMD). Recently, we reported that the BMD decreased significantly within 12 months after gastrectomy for gastric cancer in both male and female patients, but there was no significant gender-related difference in the rate of change in BMD. More than 1 year after gastrectomy, the steep decrease in the BMD stabilized and normal levels of 1,25(OH)2 vitamin D3 were maintained, despite the lack of precursor for 1,25(OH)2 vitamin D3 synthesis after gastrectomy. Alendronate therapy might be effective and prevent postgastrectomy metabolic bone disorders; however, the optimal treatment and prevention strategy for this bone disorder has not been delineated.

DOI： 10.1007/s00595-021-02253-1

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DOI： 10.1111/ped.15243

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BACKGROUND: We investigated the influence of the preoperative Controlling Nutritional Status (CONUT) score on survival and recurrence of gastric cancer in patients after curative treatment. PATIENTS AND METHODS: This study included 331 patients who underwent curative surgery followed by adjuvant treatment for gastric cancer between 2013 and 2017. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 1-, 3- and 5-year survival rates, a CONUT score of 2 was regarded as the optimal cut-off value for classification. The 3- and 5-year OS rates were 93.6% and 88.6%, respectively in the low-CONUT group, and 82.7% and 73.6% in high-CONUT group (p=0.022). The 3- and 5-year RFS rates were 78.8% and 68.7%, respectively, in the low-CONUT group, and 89.3% and 86.6%, respectively, in the high-CONUT group (p=0.05). A multivariate analysis showed that the CONUT score was a significant independent predictive factor for OS and RFS. CONCLUSION: The CONUT score was a predictive factor for survival in patients who underwent curative treatment for gastric cancer. It is necessary to develop an effective plan for perioperative care and surgical strategy according to the CONUT score.

DOI： 10.21873/invivo.12784

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BACKGROUND/AIM: Perioperative nutrition and inflammation affect the oncological outcomes of various malignancies. We evaluated the clinical impact of the preoperative platelet-to-albumin ratio (PAR) in resectable esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the PAR at 80×103 in the present study. Among 168 patients, 134 (79.8%) were defined as the PAR-low and 34 (20.2%) as the PAR-high group. The 3- and 5-year OS rates were 60.2% and 51.7% in the PAR-low group and 30.2% and 18.9% in the PAR-high group, respectively. There were significant differences in OS (p=0.005). The PAR was therefore selected for the final multivariate analysis model [hazard ratio=1.997, 95% confidence interval (CI)=1.230-3.241, p=0.037]. On comparing the perioperative clinical course between the PAR-high and PAR-low groups, there were marginally significant differences in the postoperative surgical complications and intraoperative blood loss between the groups. CONCLUSION: The PAR had clinical influence on the long-term oncological outcomes of esophageal cancer patients and might thus be a promising prognostic factor for esophageal cancer patients.

DOI： 10.21873/invivo.12909

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BACKGROUND/AIM: The albumin-bilirubin (ALBI) score, which evaluates the perioperative liver function, was developed, and had a clinical impact on both the short- and long-term oncological outcomes in some malignancies. We evaluated the clinical impact of preoperative albumin-bilirubin status in patients with resectable esophageal cancer who received curative treatment. PATIENTS AND METHODS: The study included 121 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7. Eighty patients were classified into the ALBI-low group (ALBI score <-2.7), 41 patients were categorized into the ALBI-high group (ALBI score >-2.7). The 3- and 5-year OS rates were 62.2% and 53.2%, respectively, in the ALBI-low group, and 42.2% and 35.2% in the ALBI-high group. There was a significant difference in OS (p=0.0113). The 3- and 5-year RFS rates were 43.1% and 40.3%, respectively, in the ALBI-low group and 37.7% and 26.1% in the ALBI-high group. There was a significant difference in RFS (p=0.048). When comparing the perioperative clinical course between the ALBI-high and ALBI-low groups, the incidence of postoperative anastomotic leakage was 46.3% (19/41) in the ALBI-high group, and 27.5% (22/80) in the ALBI-low group (p=0.038). CONCLUSION: The ALBI status had a clinical impact on both OS and RFS in esophageal cancer patients. Therefore, ALBI may have potential application as a prognostic factor for esophageal cancer patients.

DOI： 10.21873/invivo.12847

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BACKGROUND: Perioperative systemic inflammation affects the long-term oncological outcomes of patients with malignancies. We evaluated the clinical impact of the preoperative platelet-to-lymphocyte ratio (PLR) in patients with resectable esophageal cancer who received curative treatment. PATIENTS AND METHODS: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value of the PLR at 150 in the present study. Among 168 patients, 78 patients (46.4%) were categorized into the PLR-low group and 90 patients (53.6%) were categorized into the PLR-high group. The 3- and 5-year OS rates were 64.4% and 53.8%, respectively, in the PLR-low group, and 46.9% and 38.1% in the PLR-high group; the difference in OS was significant (p=0.046). PLR was therefore selected for the final multivariate analysis model (hazard ratio=1.553, 95% confidence interval=1.026-2.350, p=0.037). When the perioperative clinical course was compared between the two groups, the incidence of grade 2 or more anastomotic leakage after surgery was significantly lower in the PLR-low group at 26.9% compared to 43.3% in the PLR-high group (p=0.027). CONCLUSION: The PLR had a clinical impact on the long-term oncological outcomes of patients with esophageal cancer treated with curative intent. Therefore, the PLR might be a promising prognostic factor for patients with esophageal cancer.

DOI： 10.21873/invivo.12912

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BACKGROUND/AIM: To clarify the clinical significance of measuring the mean corpuscular volume (MCV) of red blood cells before applying neoadjuvant chemotherapy (NAC) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who will receive NAC followed by curative resection. PATIENTS AND METHODS: We retrospectively investigated 169 eligible patients at the Kanagawa Cancer Center between 2011-2018. The patients were divided into high and low-MCV groups. The cutoff value of the MCV was determined by the maximum χ2 statistic value on the log-rank test and was set at 92.8 fl. Clinicopathological features and outcomes were compared between the two groups. RESULTS: There was no significant association between the MCV and clinicopathological features. Both five-year recurrence-free survival (RFS) and overall survival (OS) in the high-MCV group were significantly poorer than those in the low-MCV group (RFS, p=0.026; OS, p=0.006). On multivariate analysis, a high-MCV was an independent predictive survival factor for RFS [hazard ratio (HR)=1.728; 95% confidence interval (CI)=1.033-2.891; p=0.037] and OS (HR=1.836; 95%CI=1.002-3.365; p=0.049). CONCLUSION: Measurement of the MCV before NAC may be a useful prognostic biomarker in patients with locally advanced ESCC who will receive NAC followed by curative resection.

DOI： 10.21873/invivo.12969

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INTRODUCTION: Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic-assisted (LA) and open (OP) colectomy; however, patients with transverse colon cancer were not analyzed. The aim of this study was to confirm the oncological safety and the advantages of the short- and long-term results of LA surgery for transverse colon cancer in comparison to OP surgery. MATERIALS AND METHODS: The study data were retrospectively collected from the databases of four hospitals. Patients with transverse colon cancer who underwent LA or OP R0 or R1 resection were registered. RESULTS: Among the 204 patients, 149 underwent OP colectomy and 55 underwent LA colectomy. The median follow-up period was 43 months. The rate of conversion to OP resection was 7.3%. The 5-year overall survival rate of the LA group was higher than that of the OP surgery group for all-stage patients (97.5% vs. 91.1%, P = 0.108), and it was similar in Stage II and Stage III patients (94.1% vs. 94.2%, P = 0.510). The LA group had significantly lower blood loss and a significantly longer operative time in comparison to the OP surgery group. Furthermore, the postoperative hospital stay was significantly shorter (9 vs. 13 days, P = 0.001) and the incidence of Grade ≥III complications was lower in the LA group (3.7% vs. 14.8%, P = 0.031). CONCLUSION: We concluded that LA surgery for transverse colon cancer is oncologically safe and yields better short-term results in comparison to OP surgery.

DOI： 10.4103/jcrt.JCRT_946_20

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BACKGROUND/AIM: The present study evaluated the clinical characteristics and prognostic factors of gastric cancer (GC) patients with synchronous and metachronous other primary cancer who received curative treatment for GC. PATIENTS AND METHODS: The study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A total of 244 patients were included in this study. Among them, 58 patients were diagnosed with synchronous and metachronous other primary cancer. When comparing the patient background characteristics and clinical course between GC patients without and with synchronous and metachronous other primary cancer, the background, postoperative surgical complications, and details of adjuvant treatment were similar between the two groups. The 3- and 5-year OS rates in GC patients with synchronous and metachronous other primary cancer were 69.7% and 48.0%, respectively, while those in patients without synchronous and metachronous other primary cancer were 80.6% and 74.3%, respectively, showing a statistically significant difference (p<0.001) The synchronous and metachronous other primary cancer status was included in the final multivariate analysis model (hazard ratio=2.201; 95% confidence interval=1.229-3.942; p=0.008). CONCLUSION: Synchronous and metachronous other primary cancer status is a prognostic factor in GC patients. Therefore, synchronous and metachronous other primary cancer patients need both other primary cancer and GC follow-up to improve their survival.

DOI： 10.21873/invivo.12987

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BACKGROUND/AIM: The systemic inflammation score (SIS) is a promising tool for the evaluation of prognosis. The present study aimed to evaluate the clinical impact of the preoperative SIS status in gastric cancer (GC) patients who underwent curative resection. PATIENTS AND METHODS: This study retrospectively analyzed 258 patients with primary gastric cancer who received curative treatment at Yokohama City University. The SIS was evaluated before surgery as determined by the lymphocyte-to-monocyte ratio (cut-off value=4.44) and serum albumin level (cut-off value=4.0 g/dl). RESULTS: A high SIS was identified as an independent predictor of overall survival [hazard ratio (HR)=1.784, p<0.05] and multivariate analysis showed marginal significance for recurrence-free survival (HR=1.710, p<0.05). CONCLUSION: The preoperative SIS score was correlated with both the OS and RFS of GC patients, as well as the clinical course of adjuvant chemotherapy. Thus, the SIS score is a promising prognostic factor for GC.

DOI： 10.21873/cdp.10152

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BACKGROUND/AIM: We investigated the association of the preoperative lymphocyte-to-C-reactive-protein ratio (LCR) with gastric cancer survival and recurrence after curative treatment. PATIENTS AND METHODS: This study included 480 patients who underwent curative surgery followed by adjuvant treatment for gastric cancer between 2013 and 2017. The prognostic factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A LCR of 7,000 was regarded as the optimal critical point of classification, considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 84.4% and 73.9% in the low-LCR group, respectively, and 92.4% and 87.0% in the high-LCR group, respectively, and were statistically significantly different. The RFS rates at 3 and 5 years after surgery were 78.8% and 68.7% in the low-LCR group, respectively, and 89.3% and 86.6% in the high-LCR group, respectively, with a statistically significant difference. A multivariate analysis showed that the LCR was a significant independent prognostic factor for both OS and RFS. CONCLUSION: The LCR was a significant prognostic factor for survival in patients who underwent curative treatment for gastric cancer.

DOI： 10.21873/invivo.12728

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BACKGROUND/AIM: The present study investigated the clinical impact of the lymph node ratio (LNR) on overall survival (OS) and recurrence-free survival (RFS) in cancer patients with lymph node metastasis who received curative treatment. PATIENTS AND METHODS: Eighty-six patients who received curative surgery for gastric cancer between 2000 and 2015, and in whom lymph node metastasis was pathologically confirmed, were included in this study. The LNR was defined as the ratio of the number of metastatic lymph nodes to the total number of harvested lymph nodes. RESULTS: A lymph node ratio of 0.23 was considered the optimal cutoff point for classification according to OS. Statistically significant differences were observed in the 3- and 5-year OS rates and 3- and 5-year RFS rates. The 3-year and 5-year OS rates in the LNR <0.23 group were 57.6% and 57.6%, respectively, whereas those in the LNR ≥0.23 group were 33.0% and 0% (p<0.001). The 3-year and 5-year RFS rates in the LNR <0.23 group were 45.9% and 43.6%, respectively, whereas those in the LNR >0.23 group were 25.2% and 0% (p=0.002). Regarding the site of first relapse, the incidence rates of peritoneal and lymph node metastasis in the LNR >0.23 group were significantly different in comparison to the LNR <0.23 group. CONCLUSION: A high LNR was associated with significantly worse OS and RFS in patients who received curative treatment for gastric cancer. The lymph node metastasis status should be utilized in the development of treatment strategies for gastric cancer.

DOI： 10.21873/invivo.12792

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In recent years, the radial incision and cutting(RIC)method has been developed as a treatment for intractable anastomotic stenosis after esophageal cancer surgery, and its usefulness is attracting attention. We report a case in which the RIC method was effective for endoscopic balloon dilatation-resistant anastomotic stenosis. The case was a 69-year-old woman. Transthoracic esophagectomy with three-field lymph node dissection, and narrow gastric tube reconstruction through antethoracic route, were performed for middle thoracic esophageal cancer. The patient suffered from Grade Ⅲa anastomotic leakage, but was discharged relieved. After discharge, the patient needed regular endoscopic balloon dilation for against intractable anastomotic stenosis. RIC was performed for the patient. Although stenosis relapsed after the RIC, the pain during balloon dilatation improved and oral intake can be continued without surgery. The required interval of dilatation was about 2 weeks before RIC, but it has been gradually extended to about 4 weeks after 1 year after the RIC. Moreover, oral intake and body weight of the patient were increased. The RIC method may be useful for intractable anastomotic stenosis after esophageal cancer surgery, and further case accumulation is needed.

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BACKGROUND: The lymph node (LN) ratio (LNR) has been proposed as a sensitive prognosticator in patients with esophageal squamous cell carcinoma (ESCC), especially when the number of LNs harvested is insufficient. We investigated the association between the LNR and survival in patients with locally advanced ESCC who received neoadjuvant chemotherapy (NAC) and explored whether the LNR is a prognosticator in these patients when stratified by their response to NAC. METHODS: We retrospectively reviewed 199 locally advanced ESCC patients who received curative resection after NAC between January 2011 and December 2019. The predictive accuracy of the adjusted X-tile cut-off values for LNR of 0 and 0.13 was compared with that in the Union for International Cancer Control pathological N (UICC pN) categories. The association between survival rate and clinicopathological features was examined. RESULTS: Multivariate analysis identified that the LNR was an independent risk factor for recurrence-free survival [RFS; hazard ratio (HR) 6.917, p < 0.001] and overall survival (OS) (HR 4.998, p < 0.001). Moreover, even when stratified by response to NAC, the LNR was a significant independent risk factor for RFS and OS (p < 0.001). The receiver operating characteristic curves identified that the prognostic accuracy of the LNR tended to be better than that of the UICC pN factor in all cases and responders. CONCLUSION: The LNR had a significant prognostic value in patients with locally advanced ESCC, including in those who received NAC.

DOI： 10.1245/s10434-021-10240-6

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BACKGROUND/AIM: The number of patients who have cardiovascular-morbidities and use antiplatelet and/or anticoagulation therapy is rapidly growing worldwide. The present study evaluated the safety and feasibility of gastrectomy for gastric cancer in patients who received antiplatelet and/or anticoagulation therapy in the perioperative period. PATIENTS AND METHODS: Cases were selected from the medical records of consecutive patients who were diagnosed with gastric cancer and underwent complete resection at the Kanagawa Cancer Center from 2013 to 2017. The patients were divided into the antiplatelet and/or anticoagulation treatment group and the non-antiplatelet and/or anticoagulation treatment group. RESULTS: Five hundred and six patients underwent gastrectomy for gastric cancer and were analyzed in the present study. Among them, 62 patients (12.3%) received anticoagulation therapy (anticoagulation group). When the anticoagulation and non-anticoagulation groups were compared, although there were some differences in patient background factors, the surgical findings, perioperative clinical course, and details of postoperative complications were similar. The incidence of postoperative bleeding was 0.8% (4/506) in all patients. The incidence of postoperative bleeding was 1.6% (1/62) in the anticoagulation group and 0.7% (3/446) in the non-anticoagulation group. Preoperative anticoagulation therapy was not identified as a significant independent risk factor for postoperative bleeding. CONCLUSION: These results suggest that curative gastrectomy for gastric cancer is safe and feasible, regardless of the perioperative use of antiplatelet and/or anticoagulation treatment. In addition, the perioperative use of antiplatelet and/or anticoagulation treatment was not a significant risk factor for postoperative bleeding after gastrectomy for gastric cancer.

DOI： 10.21873/anticanres.15375

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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AIM: D3 lymph node dissection (LND) for stage II and III colon cancer has been shown to improve prognosis, however, it generally increases surgical stress. Studies have reported that the C-reactive protein/albumin ratio (CAR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis for with various types of cancer. Our purposes were to assess the short- and long-term outcomes of D3 LND in patients with a high preoperative CAR (≥ 0.04). PATIENTS AND METHODS: This was a retrospective cohort analysis reviewing a prospectively collected database of Yokohama City University and three affiliated hospitals. A total of 449 patients with stage II or III colon cancer with high CAR who underwent primary resection with D2 or D3 LND were identified between 2008 and 2020. The primary and secondary outcomes of interests were the 3-year recurrence-free survival and postoperative complication rates. RESULTS: After propensity matching, 230 patients were evaluated. There was no significant difference between the D3 and D2 groups in the rate of postoperative complications overall (14.8% versus 11.3%, p=0.558), however, the incidence of anastomotic leakage tended to be greater in the D3 group (9.6% versus 2.6%, p=0.050). The long-term findings showed that there was no significant difference between the two groups (3-year recurrence-free survival rate: 77.2% versus 77.2%, p=0.880). CONCLUSION: D3 LND did not improve survival outcomes for patients with colon cancer with a poor CAR in this study. D2 LND may be a treatment option for patients with stage II-III colon cancer with a high preoperative CAR.

DOI： 10.21873/anticanres.15326

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Language：English   Publisher：(一社)日本癌治療学会  

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BACKGROUND/AIM: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. CONCLUSION: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.

DOI： 10.21873/anticanres.15259

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Language：Japanese   Publisher：(一社)日本大腸肛門病学会  

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BACKGROUND: Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index. METHODS: We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1-2; Group 2: NPS = 3-4). We compared the clinicopathological characteristics and survival rates among the groups. RESULTS: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P < 0.001). The NPS was superior to other systemic inflammatory and nutritional index for predicting prognoses, as determined using area under the curves (P < 0.05). Multivariate analysis demonstrated that the NPS was a significant predictor of poor RFS (Group 1: hazard ratio [HR] 1.897, P = 0.049; Group 2: HR 3.979, P < 0.001) and OS (Group 1: HR 2.152, P = 0.033; Group 2: HR 3.239, P = 0.006). CONCLUSIONS: The present study demonstrated that NPS was an independent prognostic factor in patients with locally advanced ESCC and more reliable and accurate than the other systemic inflammatory and nutritional index.

DOI： 10.1245/s10434-020-09549-5

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DOI： 10.1245/s10434-021-10301-w

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BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

DOI： 10.21873/anticanres.15146

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INTRODUCTION: Laparoscopic gastrectomy has become a standard procedure for treatment of gastric cancer, and hence, the opportunity for trainees to perform open gastrectomies may decrease. We investigated whether laparoscopic distal gastrectomy, performed by surgical trainees without sufficient experience performing open gastrectomies, was feasible and safe. PATIENTS AND METHODS: We compared short-term outcomes in patients when laparoscopic distal gastrectomies were performed by experienced trainees (ET group; n = 124) and inexperienced trainees (IT group; n = 98) from 2013 to 2019. RESULTS: The operation time was significantly shorter in the ET group (median time: 253 minutes vs 286 minutes, P < 0.001). The incidence of grade ≥ 2 postoperative complications did not differ significantly between the groups. In the multivariate analysis, experience performing open gastrectomies was not an independent predictor of postoperative complications. CONCLUSION: Laparoscopic distal gastrectomies performed by trainees, with insufficient experience performing open gastrectomies, are as feasible and safe as that performed by ET.

DOI： 10.1111/ases.12901

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. METHODS: Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. RESULTS: A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3-16.0), the median OS was 45.4 months (95% CI 37.4-NA), and the RR was 56.0% (95% CI 42.3-68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). CONCLUSIONS: First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

DOI： 10.1007/s00280-021-04232-2

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BACKGROUND: The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs. METHODS: The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor. RESULTS: Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05). CONCLUSION: LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.

DOI： 10.1245/s10434-020-09433-2

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AIM: To compare the mid-term oncological results between patients with low rectal cancer who underwent minimally invasive laparoscopic surgery (MILS) and those who underwent open surgery (OS). PATIENTS AND METHODS: Overall, 262 matched patients who underwent primary resection for low rectal cancer between 2000 and 2019 were divided into MILS (n=131; n=107, conventional laparoscopic surgery; n=24, robotic surgery) and OS (n=131) groups. The short- and mid-term outcomes were compared. RESULTS: Similar baseline characteristics were noted. The operative time was longer and blood loss was lesser in the MILS group; the conversion rate was 3.8%. The incidence of postoperative complications was similar. The 2-year cumulative incidence of local recurrence was noted to be much lower in the MILS group (1.9%) than in the OS group (8.4%). MILS had a significantly low hazard ratio (0.208, p=0.036). CONCLUSION: MILS has potential benefits in reducing local recurrence of low rectal cancer.

DOI： 10.21873/anticanres.15042

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The standard treatment for gastrointestinal cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastrointestinal cancer leads to body composition changes. Body composition changes, such as skeletal muscle loss and body weight loss, during multidisciplinary treatment result in poor physical activity, severe toxicity of chemotherapy and/or radiation therapy, and poor oncological outcomes. Therefore, the hypothesis is that minimization of body composition changes during multidisciplinary treatment in gastrointestinal cancer patients, the continuation of postoperative adjuvant treatment in these patients might improve, thereby improving the oncological outcomes. Given this hypothesis, recent studies have focused on introducing perioperative oral nutritional treatment for gastrointestinal cancer patients. Thus far, oral nutritional treatment has proven promising and showed some clinical benefits for gastrointestinal cancer patients during the perioperative period. However, whether or not oral nutritional treatment has clinical benefits on the long-term oncological outcomes in gastrointestinal cancer remains unclear. To optimize oral nutritional treatment for gastrointestinal cancer patients, it is necessary to clarify the benefits of oral nutritional treatment on the long-term oncological outcomes in gastric cancer patients and establish the optimal approach to oral nutritional treatment.

DOI： 10.21873/anticanres.14937

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BACKGROUND/AIM: Stanniocalcin2 (STC2) is associated with proliferation, invasion, and metastasis in various cancers. We examined the clinical significance of STC2 mRNA expression in patients with colorectal cancer (CRC). PATIENTS AND METHODS: Relative expression levels of STC2 mRNA in CRC tissues and corresponding normal mucosa obtained from 202 patients were measured using quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: Expression of STC2 mRNA was higher in the cancer tissue than in the adjacent normal mucosa. STC2 mRNA expression in cancer tissues was associated with tumour size, liver metastasis, venous invasion, and lymph node metastasis. High expression of STC2 mRNA was significantly associated with poorer postoperative survival (p=0.0003). Multivariate analysis showed that high expression of STC2 mRNA was an independent predictor of postoperative survival. CONCLUSION: High expression of STC2 mRNA in CRC tissue may be a useful prognostic marker in patients with CRC.

DOI： 10.21873/anticanres.14983

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The patient was a 59‒year‒old woman. In 2005, she underwent low anterior resection plus D2 dissection for rectal cancer (pT4aN2aM0, pStage Ⅲb). In 2007, she underwent hepatic S8 subsegment resection for liver metastasis. After that, FOLFIRI therapy was performed as chemotherapy for recurrence of the right upper lung lobe and para‒aortic lymph node(PALN). CR was once obtained in both(of)PALN and lung, but PALN re‒expansion and left ovary enlargement were observed in 2009, and resection of PALN plus left ovariectomy was performed. Histological examination showed PALNs were metastases from rectal cancer and the ovary was benign. Eleven years after the first operation, she stayed alive without recurrence.

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BACKGROUND: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. METHODS: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. RESULTS: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. CONCLUSIONS: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

DOI： 10.1093/jjco/hyaa221

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It is well known that surgery is the mainstay treatment for duodenal adenocarcinoma. However, the optimal extent of surgery is still under debate. We aimed to systematically review and perform a meta-analysis of limited resection (LR) and pancreatoduodenectomy for patients with duodenal adenocarcinoma. A systematic electronic database search of the literature was performed using PubMed and the Cochrane Library. All studies comparing LR and pancreatoduodenectomy for patients with duodenal adenocarcinoma were selected. Long-term overall survival was considered as the primary outcome, and perioperative morbidity and mortality as the secondary outcomes. Fifteen studies with a total of 3166 patients were analyzed; 995 and 1498 patients were treated with limited resection and pancreatoduodenectomy, respectively. Eight and 7 studies scored a low and intermediate risk of publication bias, respectively. The LR group had a more favorable result than the pancreatoduodenectomy group in overall morbidity (odd ratio [OR]: 0.33, 95% confidence interval [CI] 0.17-0.65) and postoperative pancreatic fistula (OR: 0.13, 95% CI 0.04-0.43). Mortality (OR: 0.96, 95% CI 0.70-1.33) and overall survival (OR: 0.61, 95% CI 0.33-1.13) were not significantly different between the two groups, although comparison of the two groups stratified by prognostic factors, such as T categories, was not possible due to a lack of detailed data. LR showed long-term outcomes equivalent to those of pancreatoduodenectomy, while the perioperative morbidity rates were lower. LR could be an option for selected duodenal adenocarcinoma patients with appropriate location or depth of invasion, although further studies are required.

DOI： 10.1007/s10147-020-01840-5

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BACKGROUND: This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer. METHODS: This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed. RESULTS: Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966). CONCLUSION: Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.

DOI： 10.1186/s12957-021-02155-z

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Osteosarcoma (OS) is an aggressive mesenchymal tumor for which no molecularly targeted therapies are available. We have previously identified TRAF2- and NCK-interacting protein kinase (TNIK) as an essential factor for the transactivation of Wnt signal target genes and shown that its inhibition leads to eradication of colorectal cancer stem cells. The involvement of Wnt signaling in the pathogenesis of OS has been implicated. The aim of the present study was to examine the potential of TNIK as a therapeutic target in OS. RNA interference or pharmacological inhibition of TNIK suppressed the proliferation of OS cells. Transcriptome analysis suggested that a small-molecule inhibitor of TNIK upregulated the expression of genes involved in OS cell metabolism and downregulated transcription factors essential for maintaining the stem cell phenotype. Metabolome analysis revealed that this TNIK inhibitor redirected the metabolic network from carbon flux toward lipid accumulation in OS cells. Using in vitro and in vivo OS models, we confirmed that TNIK inhibition abrogated the OS stem cell phenotype, simultaneously driving conversion of OS cells to adipocyte-like cells through induction of PPARγ. In relation to potential therapeutic targeting in clinical practice, TNIK was confirmed to be in an active state in OS cell lines and clinical specimens. From these findings, we conclude that TNIK is applicable as a potential target for treatment of OS, affecting cell fate determination.

DOI： 10.1172/jci.insight.137245

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BACKGROUND: Most evidence regarding lateral lymph node dissection for rectal cancer is from expert settings. This study aimed to evaluate the safety and efficacy of this procedure in a practice-based cohort. METHODS: A total of 383 patients who were diagnosed with stage II-III mid-to-low rectal cancer between 2010 and 2019 and underwent primary resection with curative intent at a general surgery unit were retrospectively reviewed. After propensity matching, 144 patients were divided into the following groups for short- and long-term outcome evaluation: mesorectal excision with lateral lymph node dissection (n = 72) and mesorectal excision (n = 72). RESULTS: This practice-based cohort was characterized by a high pT4 (41.6%) and R1 resection (10.4%) rate. Although the operative time was longer in the lateral dissection group (349 min vs. 237 min, p < 0.001), postoperative complications (19.4% vs. 16.7%, p = 0.829), and hospital stay (18 days vs. 22 days, p = 0.059) did not significantly differ; 5-year relapse-free survival (62.5% vs. 66.4%, p = 0.378), and cumulative local recurrence (9.7% vs. 15.3%, p = 0.451) were also in the same range in both groups. In the seven locally recurrent cases in the lateral dissection group, four had undergone R1 resection. CONCLUSIONS: Lateral lymph node dissection was found to be safe in this practice-based cohort; however, the local control effect was not obvious. To maximize the potential merits of lateral lymph node dissection, strategies need to be urgently established to avoid R1 resection in clinical practice.

DOI： 10.1186/s12893-021-01053-1

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Language：Japanese   Publisher：横浜市立大学医学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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BACKGROUND/AIM: The changes of dietary intake (DI) after gastrectomy have not been objectively reported. It has not been clear how much DI loss is experienced after total gastrectomy (TG) in comparison to after distal gastrectomy (DG). This study quantified the changes of DI after gastrectomy, and clarified how much DI loss is experienced after TG. PATIENTS AND METHODS: This was a prospective observational study. Patients who underwent gastrectomy for gastric cancer were enrolled. The DI loss was evaluated at 1 and 3 months postoperatively. RESULTS: Thirty-three patients underwent TG, and 117 patients underwent DG. The median %DI loss of the overall study population at 1 and 3 months after surgery was -9.3% and -3.6%. The median %DI loss at 1 and 3 months postoperatively was -15.6% and -5.3% in TG group, -8.9% and -3.3% in DG group (p=0.10 and 0.49, respectively). CONCLUSION: The patients experienced DI loss of approximately 10% at 1 month after gastrectomy. Patients who received TG tended to show a greater %DI loss at 1 month postoperatively.

DOI： 10.21873/invivo.12514

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BACKGROUND: The aim of the present study was to determine the utility of the C-reactive protein-to-albumin ratio (CAR) for predicting the overall survival (OS) in locally advanced colorectal cancer (CRC) patients. PATIENTS AND METHODS: This retrospective multicenter study was performed using data from a prospectively maintained database of pathological Stage II or III patients undergoing CRC surgery at the Yokohama City University, Department of Surgery, and its affiliated institutions between April 2000 and March 2016. The risk factors for the OS were identified. RESULTS: A CAR of 0.03 was considered to be the optimal cutoff point for classification based on the 1-, 3-, and 5-year survival rates and receiver operating characteristic curve. The OS rates at 3 and 5 years after surgery were 92.4% and 85.7% in the CAR-low group, respectively, and 86.7% and 81.1% in the CAR-high group. A multivariate analysis showed that the CAR was a significant independent risk factor for the OS. When comparing the patients' demographic and clinical characteristics between the CAR ≤0.03 and >0.03 groups, the incidence of patients who received adjuvant chemotherapy and the incidence of postoperative complications were significantly different between the two groups. CONCLUSION: The present study showed that the preoperative CAR was a risk factor for the OS in patients who underwent surgery for CRC. To improve the patients' survival, CAR might be a useful tool for devising treatment strategies.

DOI： 10.4103/jcrt.JCRT_355_19

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BACKGROUND: Resection of the primary lesion with radical lymph node dissection is the most promising treatment avenue for patients with cancer. On the other hand, these procedures often induce excessive intraoperative blood loss (IBL) and require perioperative blood transfusion. The influence of IBL on the long-term postoperative outcomes of patients with digestive cancer is controversial. We investigated the impact of IBL on survival and recurrence after curative surgery in patients with colorectal cancer (CRC) in a single study group. PATIENTS AND METHODS: In total, 1,597 patients who underwent radical resection for CRC at three group hospitals between 2000 and 2019 were reviewed. Patients were classified into a group with high IBL (≥200 ml) or low IBL (<200 ml). The risk factors for disease-free (DFS) and overall (OS) survival were analyzed. RESULTS: A total of 489 and 1,108 patients were classified into the high and low IBL groups, respectively. The OS and DFS rates at 5 years after surgery were 89.3% and 63.4%, respectively, for the high IBL group and 96.9% and 77.8% for the low IBL group; these differences were statistically significantly (p<0.001). The multivariate analysis demonstrated that IBL was a significant independent risk factor for OS and DFS. CONCLUSION: The amount of IBL was associated with significant differences in the OS and DFS of patients with stage II/III CRC who received curative resection. The surgical procedure, surgical strategy, and perioperative care should be carefully planned to avoid causing IBL.

DOI： 10.21873/invivo.12649

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BACKGROUND: We investigated the impact of the pre-surgical C-reactive protein-to-albumin ratio (CAR) on survival and recurrence after curative treatment for gastric cancer. PATIENTS AND METHODS: This study included 481 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. RESULTS: A CAR of 0.05 was regarded as the optimal critical point of classification considering the 3- and 5-year survival rates and patients were divided according to their CAR. The OS rates at 3 and 5 years after surgery were significantly higher at 92.5% and 87.9%, respectively, in the low-CAR group compared with 84.9% and 71.9%, respectively, in the high-CAR group. The corresponding RFS rates were 89.1% and 85.5%, and 81.0% and 72.2%, respectively, also a significant difference. A multivariate analysis demonstrated that the CAR was a significant independent risk factor for the OS and marginally significant independent risk factor for the RFS. In addition, the incidences of pancreatic fistula and abdominal abscess were significantly higher and the rate of introduction of adjuvant chemotherapy significantly lower in the high-CAR group. CONCLUSION: The CAR was a risk factor influencing survival in patients who underwent curative treatment for gastric cancer. An effective perioperative care plan and surgical strategy need to be developed according to the CAR.

DOI： 10.21873/invivo.12648

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BACKGROUND: The aim of the present study was to evaluate the efficacy of TJ-107 for oxaliplatin-induced peripheral neurotoxicity in prospective, multi-institutional, randomized, double-blind, placebo-controlled Phase II trials using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire (FACT-GOG-NTX-12). PATIENTS AND METHODS: The patients who were registered to the Goshajinkigan oxaliplatin neurotoxicity evaluation study (UMIN000002211) were analyzed. A NTX-12 from the validated FACT/GOG-NTX-12 was assessed before treatment and at the end of every 2 cycles. RESULTS: The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). CONCLUSION: There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin.

DOI： 10.4103/jcrt.JCRT_1123_19

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AIM: Recent studies have reported that the albumin-to-globulin ratio (AGR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis in various types of patients with cancer. However, its prognostic value in patients with esophageal cancer is still unclear. We aimed to examine the utility of the AGR for predicting the short- and long-term outcomes in patients with esophageal cancer who underwent curative resection. PATIENTS AND METHODS: This was a retrospective cohort analysis reviewing the medical records of consecutive patients who underwent esophagectomy for clinical stage I to III esophageal cancer at Yokohama City University. A total of 105 patients were identified between 2005 and 2018. The overall survival (OS), recurrence-free survival (RFS), and postoperative complication rates were compared between patients with high AGR (>1.48) and those with low AGR (≤1.48) group. RESULTS: A total of 57 and 48 patients were classified into the high and low AGR groups, respectively. There was no significant difference between the two groups in the rate of overall postoperative complications of more than Clavien-Dindo grade 3 (50.9% vs. 54.2%, p=0.85). The long-term findings showed that 5-year OS and RFS rates were significantly better for the group with a high AGR (67.2% vs. 33.8%, p<0.001 and 51.6% vs. 28.5%, p=0.003, respectively). CONCLUSION: This study suggests that a low preoperative AGR is a risk factor for poor RFS and OS in patients who are planning to undergo curative surgery for esophageal cancer. AGR may be a useful biomarker for establishing treatment strategies to improve patients' survival.

DOI： 10.21873/invivo.12658

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BACKGROUND/AIM: We hypothesised that the prognostic nutrition index (PNI) is useful for evaluating host immunity and response to immune checkpoint inhibitors. We investigated the effect of PNI on nivolumab monotherapy efficacy in advanced or recurrent gastric cancer (GC) or gastro-oesophageal junction cancer (GOC) patients. PATIENTS AND METHODS: We retrospectively examined 110 patients, divided them into a high-PNI group and a low-PNI group, and compared treatment efficacy, adverse events (AEs), and survival between the groups. RESULTS: Median overall survival (OS) was significantly longer in the high-PNI group than in the low-PNI group (205 vs. 109 days; p<0.001). Multivariate analysis revealed that low PNI was an independent risk factor for OS (hazard ratio=2.398; 95% confidence interval=1.384-4.154; p=0.002). The overall response rate and frequency of AEs were not significantly different between the groups. CONCLUSION: PNI could be a useful prognostic factor in GC or GOC patients undergoing nivolumab monotherapy.

DOI： 10.21873/invivo.12292

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BACKGROUND/AIM: This study was designed to investigate gender-related differences in changes in bone metabolism after gastric cancer surgery. PATIENTS AND METHODS: We prospectively recruited 47 patients (38 males and 9 females) who had early gastric cancer. The bone mineral density (BMD), serum levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), and estradiol (E2) were measured before and after surgery. RESULTS: BMD significantly decreased 12 months after surgery by median degrees of 3.4% and 3.9% in male and female patients, respectively (p<0.001 and p=0.023). There was no significant difference between both genders in the rate of change in BMD after surgery. The serum E2 level in male patients significantly increased by a median value of 22 pg/ml 12 months after gastrectomy (p=0.030). Both the serum 25(OH)VD and 1,25(OH)2VD levels remained nearly within the normal range throughout the observation period in both male and female patients. CONCLUSION: BMD significantly decreased within 12 months after gastrectomy in both male and female patients with gastric cancer, and there was no significant gender-related difference in the rate of change in BMD.

DOI： 10.21873/invivo.12510

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Gastrectomy with D2 lymph node dissection and perioperative adjuvant treatment is the standard treatment for locally advanced gastric cancer. However, the morality rate is reported to be 20%-40% after gastrectomy for gastric cancer. Perioperative sarcopenia and obesity are strongly related to postoperative surgical complications after gastrectomy. Furthermore, recent studies have shown that postoperative surgical complications are related to long-term oncological outcomes. If we can prevent or improve perioperative sarcopenia or obesity in gastric cancer patients, the rate of postoperative surgical complications in these patients might be reduced, thereby improving the long-term oncological outcomes. Given this hypothesis, recent studies have focused on enacting perioperative exercise programs for gastric cancer patients with sarcopenia and overweight/obesity. Such exercise programs have proven promising and demonstrated some clinical benefits for gastric cancer patients with sarcopenia and overweight/obesity. However, whether or not perioperative exercise programs have clinical benefits with regard to long-term oncological outcomes in gastric cancer patients is unclear. To optimize these perioperative exercise programs for gastric cancer patients, it is necessary to clarify the benefits with regard to the long-term oncological outcomes in these patients and establish an optimal perioperative exercise program.

DOI： 10.21873/invivo.12311

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BACKGROUND/AIM: Cancer stem cells (CSCs) are reported to associated with cancer metastasis, relapse, and chemoresistance. This study examined the clinical significance of the expression of two CSC markers, the transporter associated with antigen processing 1 (TAP1) and the Delta-like 4 (DLL4) protein, in patients with locally advanced GC. PATIENTS AND METHODS: This study was performed using samples obtained from 413 pathological stage II/III GC patients after curative gastrectomy. We examined TAP1 and DLL4 expression using immunohistochemical analysis with tissue microarray and examined the association between TAP1 or DLL4 expression, clinicopathological factors and survival. RESULTS: High TAP1 expression was associated with better overall survival compared to low TAP1 expression (p=0.004). Furthermore, in multivariate analysis, high TAP1 expression was defined as a predictive factor for good survival. There was no significant difference between DLL4 expression and clinicopathological features and overall survival. CONCLUSION: TAP1 expression may be a useful prognostic marker in patients with locally advanced GC.

DOI： 10.21873/invivo.12562

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A case of 69-year-old man underwent resection for the plantar surface of left foot malignant melanoma and received a sentinel biopsy of left inguinal lymph node. Two years and 10 months later, a mass of 30 mm in diameter in the ileum was detected by contrast-enhanced computed tomography, which showed abnormal uptake using FDG positron emission tomography. The partial intestinal resection was performed, and then, the mass was diagnosed as metastasis of malignant melanoma by pathological examination. Malignant melanoma is highly malignant disease that frequently shows distant metastasis. Although the malignant melanoma with distant metastasis shows poor prognosis, previous studies reported the prognosis could be improved when the patient could receive curative resection for single intraabdominal metastasis. Therefore, surgical resection should be considered for the single metastasis of malignant melanoma. We report a case of malignant melanoma with ileum metastasis resected curatively with literature review.

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BACKGROUND: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on the pancreatic cancer survival and recurrence after curative surgery followed by adjuvant chemotherapy. PATIENTS AND METHODS: This study included 155 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: An ACCI of 8 was regarded as the optimum critical point of classification considering the 1-, 3- and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 25.7% and 19.0% in the ACCI-low group, respectively, and 7.6% and 0% in the ACCI-high group, which amounted to a statistically significant difference (P = 0.019). The RFS rates at 3 and 5 years after surgery were 17.3% and 13.8% in the ACCI-low group, respectively, and 7.1% and 0% in the ACCI-high group, which amounted to a marginally statistically significant difference (P = 0.104). A multivariate analysis showed that the ACCI was a significant independent risk factor for both the OS and RFS. CONCLUSIONS: The ACCI was a risk factor for the OS in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. An effective plan is needed for determining the optimum surgical strategy according to the ACCI.

DOI： 10.4103/jcrt.JCRT_440_18

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BACKGROUND: Intractable ascites secondary to malignant disease deteriorates patients' quality of life. The purpose of this study was to evaluate the safety and efficacy of percutaneous peritoneovenous (Denver) shunt in treating intractable malignant ascites in cancer patients. MATERIALS AND METHODS: Thirty-five patients who had undergone Denver peritoneovenous shunt for the treatment of ascites associated with malignant tumor from October 2014 to 2017 were retrospectively analyzed. The demographic characteristics, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analyses were performed. RESULTS: The sites of primary tumor were pancreatic cancer in 19 patients, bile duct cancer in 8, gallbladder cancer in 5, breast cancer in 2, and peritoneal malignant mesothelioma in 1. Palliation of abdominal distention was achieved in 29 patients (82.9%). Postoperative complications of Grade 2 or higher were seen in 11 patients (31.4%), and Grade 5 complications were observed in three patients (8.6%). Patients with a high American Society of Anesthesiologists (ASA) grade and high ascites drainage volume had a significantly higher incidence of postoperative complications than a low ASA grade and low ascites drainage volume, and a multivariate logistic analysis showed that the intraoperative ascites drainage volume was an independent risk factor for all complications. CONCLUSIONS: The Denver shunt for malignant ascites is useful for improving patients' quality of life if the indications are selected properly. Drainage of intraoperative ascites was a risk factor for postoperative complications after the Denver shunt technique in cancer patients with malignant ascites. Further experience and discussion are necessary to establish the patient selection criteria.

DOI： 10.4103/jcrt.JCRT_606_18

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A 76-year-old man with a past history of liver transplantation because of liver cirrhosis visited a hospital in October 2018 because of vomiting and abdominal pain. Although the patient underwent conservative medical treatment, no improvement of the symptoms was observed, and he received consultation at our hospital. After thorough examination, and because of the policy of inpatient treatment after the diagnosis of adhesion ileus obstruction post liver transplantation surgery, intestinal decompression was performed using an ileus tube. However, there was no improvement in the symptoms even after inserting the ileus tube, and intestinal obstruction was diagnosed in November 2018. During the preoperative examination, a tumorous shadow was found in the right lung, although it became a policy of scrutiny after improvement of the bowel obstruction. During the laparotomy, a macroscopic tumor exposed on the serosal surface was observed on the anal side at 120 cm from the Treitz ligament, and this site was considered to be the blocking origin. Partial resection of the small intestine including the blockage site was performed. The pathological result revealed the diagnosis of adenosquamous carcinoma. Furthermore, immunostaining was CK7 positive, CK20 negative, TTF-1 negative, and Napsin negative, suggesting the possibility of a metastatic tumor derived from lung cancer. The postoperative course was uneventful, and the patient was discharged on postoperative day 9. On day 30 after surgery, the left pleural effusion increased and pleural effusion cytology revealed a diagnosis of primary lung adenocarcinoma Stage Ⅳ. Considering the patient's PS, it became a best supportive care(BSC)policy after consultation with the family, and it ended on postoperative day 70. Here, we report about a case diagnosed with metastatic small bowel cancer and intestinal obstruction and conduct a literature review.

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A 63-year-old-woman was diagnosed with gastric cancer cStage ⅠA after ESD, and then, underwent robot-assisted distal gastrectomy. She vomited on the postoperative day 2 and then was inserted nasogastric tube. The amount of drainage from the tube was increased on the postoperative day 5, therefore, abdominal computed tomography scan was performed, which showed herniation of small bowel at the 8 mm port site in the left upper abdomen. The emergent surgery was performed because of difficulty in manual reduction. Intraoperative findings showed that small intestine was incarcerated at the left 8 mm port-site. The intestine was released by incising the fascia of hernia orifice, then, the fascia was repaired. There was no recurrence of gastric cancer and port-site hernia for 34 months after surgery. In general, the fascia of over 10 mm port site is sutured and closed to avoid port-site hernia, however, it is unclear whether the fascia of 8 mm port-site should be closed after robotic surgery. Since we experienced this case, we have also performed fascia suture on the 8 mm port-site in all cases. And then, we could prevent occurrence of port-site hernia in the 8 mm port-site.

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BACKGROUND: Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition). PATIENTS AND METHODS: We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared. RESULTS: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (P < 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS [M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254-4.342, P < 0.001; H-LNR: HR 5.148, 95% CI 3.546-7.474, P < 0.001] and OS (M-LNR: HR 2.749, 95% CI 2.038-3.708, P < 0.001; H-LNR: HR 4.654, 95% CI 3.288-6.588, P < 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (P < 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (P = 0.001 and < 0.001, respectively). CONCLUSIONS: High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage.

DOI： 10.1245/s10434-020-08616-1

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BACKGROUND/AIM: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. RESULTS: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. CONCLUSION: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

DOI： 10.21873/anticanres.14599

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Language：Japanese   Publisher：横浜市立大学医学会  

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BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the extrahepatic bile duct (EHBD) is very rare but is known for its aggressiveness and poor prognosis. We herein report a case of rapidly progressed NEC in the extrahepatic bile duct. CASE PRESENTATION: An 84-year-old man was referred to our facility with obstructive jaundice and abdominal pain. Imaging studies revealed an irregular filling defect in the middle bile duct by endoscopic retrograde cholangiopancreatography and an enhanced wall thickening from the middle to distal portion by enhanced computed tomography. The patient was initially diagnosed with extrahepatic cholangiocarcinoma by a bile duct biopsy and underwent pancreatoduodenectomy with lymph node dissection. The pathological findings showed an NEC with an adenosquamous carcinoma component in the extrahepatic bile duct with lymph node metastases. The patient experienced multiple liver metastases 1 month after surgery and died 3 months after surgery. Due to the rapid progression of his disease, his general condition deteriorated, and he was unable to receive any additional treatments, such as chemotherapy. CONCLUSION: As shown in our case, NEC of the EHBD has an extremely poor prognosis and can sometimes progress rapidly. Multimodality treatment should be considered, even in cases of locoregional disease.

DOI： 10.1186/s40792-020-00945-3

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND: The findings of COMPASS, a randomized phase II study, suggested that the regimens and courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (GC) did not affect the pathological response. However, pathological complete response was achieved in 10% patients who received four courses of either S-1/cisplatin or paclitaxel/cisplatin. We hypothesized that if relevant biomarkers could be used to predict the suitable NAC regimen before treatment initiation, further improvements could be ensured in the outcomes of locally advanced GC. MATERIALS AND METHODS: mRNA extraction, real-time polymerase chain reaction, and immunohistochemical analyses were performed using endoscopic biopsy specimens of primary tumors, collected prior to NAC, to determine the clinically relevant biomarkers. RESULTS: TIMP1, DSG2, RRM1, MUC2, EGFR, ZDHHC14, and CLDN18.2 were identified as biomarker candidates, since their expression was significantly associated with the pathological responses to each NAC regimen. Furthermore, TIMP1 and DSG2 were identified as predictive biomarkers of the pathological response to each NAC regimen. CONCLUSIONS: The effective prediction of the pathological response to NAC regimens in locally advanced GC using biomarkers identified from endoscopic biopsy specimens indicates the possibility of personalizing NAC based on biomarker analysis.

DOI： 10.18632/oncotarget.27658

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BACKGROUND: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer. PATIENTS AND METHODS: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses. RESULTS: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001). CONCLUSION: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer.

DOI： 10.21873/anticanres.14404

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BACKGROUND: Several immune-inflammatory markers are associated with cancer progression. The purpose of the present study was to clarify the influence of the preoperative C-reactive protein-to-albumin ratio (CRP/ALB ratio) on survival of patients with esophageal cancer and recurrence after curative resection. PATIENTS AND METHODS: The preoperative CRP/ALB ratio was evaluated in 122 patients who underwent radical resection for esophageal cancer from 2005 to 2018. The correlations between the CRP/ALB ratio and cancer-specific overall (OS), recurrence-free (RFS) survival and the clinicopathological status were analyzed. RESULTS: The optimal cut-off value of the CRP/ALB ratio determined using receiver operating characteristic curve analysis was 0.04. Patients were divided into two groups based on this cut-off value: the low CRP/ALB group (n=59) and the high CRP/ALB group (n=50). The OS rate at 5 years after surgery was significantly lower in the group with high CRP/ALB at 40.5% whilst it was 63.5% in the low CRP/ALB group (p=0.005). The corresponding RFS rates at 5 years after surgery were 32.5% and 48.3%, respectively, which was a statistically significant difference (p=0.007). A multivariate analysis showed that a high CRP/ALB ratio was a significant independent risk factor for poorer cancer-specific OS and RFS. CONCLUSION: The preoperative CRP/ALB ratio was a strong prognostic marker for patients with esophageal cancer. The surgical strategy, including procedure and perioperative care should be carefully planned for patients with a high CRP/ALB ratio.

DOI： 10.21873/anticanres.14205

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INTRODUCTION: We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients. METHODS: The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified. RESULTS: Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014). CONCLUSION: A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.

DOI： 10.1007/s10147-019-01603-x

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BACKGROUND: The aim of the present study was to evaluate the clinical impact of the perioperative use of antiplatelet/anticoagulation therapy for postoperative bleeding after esophagectomy for esophageal cancer. PATIENTS AND METHODS: Patients were selected from the medical records of consecutive patients who were diagnosed with primary esophageal adenocarcinoma or squamous cell carcinoma and who underwent complete resection at Yokohama City University from January 2005 to September 2018. The patients were divided into the antiplatelet/anticoagulation treatment group and the non-treatment group. We compared the safety and feasibility of esophagectomy between two groups. RESULTS: One hundred and twenty-two patients underwent esophagectomy for esophageal cancer and were analyzed in the present study. Among them, 18 (14.8%) received anti-thrombotic therapy (anticoagulation group). The incidence of postoperative bleeding in patients overall was 8.2% (10/122). The incidence of postoperative bleeding in the anticoagulation group was 22.2% (4/18), while that in the non-anticoagulation group was 5.8% (6/104). Preoperative anticoagulation therapy was identified as a significant independent risk factor for postoperative bleeding (hazard ratio=4.673, 95% confidence interval=1.170-18.519; p=0.029). CONCLUSION: The perioperative use of anti-thrombotic therapy was a significant risk factor for postoperative bleeding after esophagectomy for esophageal cancer. Thus, when patients receive perioperative antiplatelet/anticoagulation treatment, careful attention is required after esophagectomy due to their increased risk of postoperative bleeding.

DOI： 10.21873/anticanres.14204

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AIM: To clarify the benefits of robotic-assisted laparoscopic surgery (RALS) regarding short-term outcomes in patients with technically demanding rectal cancer (TDRC). PATIENTS AND METHODS: Between April 2015 and September 2019, 88 TDRC cases were identified from our database, and divided into the RALS (n=32) and conventional laparoscopic surgery (CLS) (n=56) groups. TDRC was defined as mid-rectal tumors presenting at least one of the following risk factors: Male sex, high body mass index, T4 stage, bulky tumor, or low rectal tumor. RESULTS: Patient baseline characteristics were similar in both groups. One and 15 patients developed anastomotic leakage in the RALS and CLS groups (3% vs. 27%, p<0.01), respectively. The postoperative complication rate was lower in the RALS group (19% vs. 43%, p=0.03). Multivariate analysis showed the surgical approach to be an independent predictor for anastomotic leakage. CONCLUSION: RALS has potential advantages to prevent anastomotic leakage complications in patients with TDRC.

DOI： 10.21873/anticanres.14201

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AIM: We examined whether the perioperative systemic inflammation score (SIS), which describes systemic inflammation and/or malnutrition, affected the tumor recurrence and survival in advanced gastric cancer patients. PATIENTS AND METHODS: The study retrospectively analyzed 160 patients with stage II/III gastric cancer who underwent curative resection at the Kanagawa Cancer Center. The SIS was evaluated before surgery, one week after surgery and one month after surgery, as determined by the serum albumin level (cut-off value=4.0 g/dl) and lymphocyte-to-monocyte ratio (cut-off value=4.44). RESULTS: A high SIS at one month after surgery was identified as an independent predictor for overall survival [hazard ratio (HR)=2.143, p=0.020] and showed a marginal significance for the relapse-free survival (HR=1.814, p=0.053) in multivariate analyses. CONCLUSION: The SIS at one month after surgery is a useful biomarker for predicting the long-term outcome in patients with advanced gastric cancer.

DOI： 10.21873/anticanres.14095

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BACKGROUND: This study aimed to investigate the impact of postoperative complications (PCs) in patients with pathological stage (pStage) II or III gastric cancer (GC) who received adjuvant chemotherapy with S-1 after curative surgery. PATIENTS AND METHODS: Altogether, data for 226 patients were examined retrospectively. The relationship between PCs and clinicopathological features and survival were examined. RESULTS: Recurrence-free survival was significantly worse in the group with PCs than in the PC-negative group. On multivariate analysis, having PCs of grade 2 or more was an independent risk factor for recurrence (hazard ratio=1.721; 95% confidence intervaI=1.014-2.920; p=0.044). In addition, for each pStage analysis, having PCs of grade 2 or more was a risk factor for recurrence even in patients with pStage II GC. CONCLUSION: PC of grade 2 or more was an independent risk factor for recurrence in patients with pStage II GC who received adjuvant chemotherapy with S-1 after curative gastrectomy. Thus, for patients with PCs, even for those with pStage II GC, more effective adjuvant chemotherapy, such as S-1 plus docetaxel, may be needed.

DOI： 10.21873/anticanres.14120

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Surgical resection and perioperative adjuvant therapy are widely accepted standard treatments for gastrointestinal cancer. However, body composition changes, such as weight loss and skeletal muscle loss, are unavoidable during these treatments. Several studies have shown that perioperative body composition changes are affected by multimodal treatment for gastrointestinal cancer. This review summarizes the background, current status, and future perspectives of perioperative body composition changes in the multimodal treatment of gastrointestinal cancer. Recent studies have described the body composition changes observed in the early period after surgery and during adjuvant therapy. Changes in the body composition might affect adjuvant chemotherapy toxicity after surgery and postoperative complications after neoadjuvant therapy. The mechanisms underlying body composition changes during multimodal therapy are multifactorial and include systemic inflammation, reduced nutrient intake, and physical inactivity. Several approaches have been tested to maintain the body composition, and especially prevent skeletal muscle wasting, during multimodal therapy. Although the ideal approach for managing body composition changes in gastrointestinal cancer patients remains unclear, recent studies support the combination of multiple approaches rather than a single approach.

DOI： 10.1007/s00595-019-01815-8

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BACKGROUND: The short- and long-term outcomes of esophagectomy for esophageal cancer were fully evaluated in patients older than 75 years of age. PATIENTS AND METHODS: The present study selected patients who received esophagectomy for esophageal cancer. Patients were divided into non-elderly patients [age <75 years (non-elderly group)] and elderly patients [age ≥75 years (elderly group)]. The postoperative surgical morbidity, postoperative 30-days mortality, recurrence-free survival (RFS), and overall survival (OS) rates were evaluated between the non-elderly group and elderly group. RESULTS: One hundred twenty-two patients were evaluated in this study. Ninety-eight patients and 24 patients were classified into the non-elderly group and elderly group, respectively. The postoperative surgical complication rates in the non-elderly and elderly groups were 71.4% and 75.0%. There was not a statistically significant difference between the two groups (p=0.710). Mortality was observed in 1 patient in the elderly group (4.2%) due to cardiovascular disease. Significant differences were observed in the five-year OS and RFS rates of the elderly and non-elderly groups (55.4% vs. 29.7%, p=0.0017 and 42.2% vs. 21.2%, p=0.0334, respectively). CONCLUSION: Although the rate of postoperative surgical complications after esophagectomy for esophageal cancer was almost equal in the elderly and the non-elderly patients, significant differences were observed in the mortality and long-term outcomes of the two groups. Thus, the surgical strategy and perioperative care must be carefully planned for esophageal cancer patients older than 75 years of age.

DOI： 10.21873/anticanres.14047

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Language：Japanese   Publisher：(株)癌と化学療法社  

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The effectiveness of lymph node dissection tends to be reduced clinically in elderly patients with colorectal cancer because of physical limitations, such as comorbidities and organ dysfunction. We investigated the influence of the level of lymph node dissection on the prognosis of elderly patients with colorectal cancer. A total of 137 patients with pT2 or more-advanced tumors or lymph node metastasis were retrospectively studied. The 5-year overall survival(OS)andrelapse free survival(RFS) rates were 74.1% and 63.9%, respectively. Lymph node dissection was an independent prognostic factor in the examination of prognostic factors of OS. In the propensity-matchedcohort, the 5-year OS rates were 87.2% and5 8.2%(p=0.02), and the 5-year RFS rates were 77.8% and4 6.4%(p=0.03)in the D3 andred ucedgroups, respectively. The D3 group hada significantly better prognosis than the reduced group. D3 lymph node dissection might contribute to the improvement of prognosis in elderly people with colorectal cancer.

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Language：Japanese   Publisher：(株)癌と化学療法社  

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BACKGROUND/AIM: To evaluate the outcomes of curative resection for Borrmann type IV gastric cancer through an analysis of the clinical, surgical and pathological data and through identifying which of these prognostic factors are associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 2798 patients who had undergone excision of the primary lesion and 122 patients with type IV gastric cancer undergoing curative resection (R0 or 1) at Yokohama City University Hospital and Kanagawa Cancer Center between November 1995 and May 2016. RESULTS: Borrmann type IV gastric cancer had more advanced and unfavorable clinicopathological factors compared to other types. The 5-year overall survival rate was 28%, and the median survival was 21.8 months. The overall survival rate was influenced by the depth of invasion, lymph node metastasis, peritoneal lavage cytology (CY), stage and intraoperative blood loss. Of these, independent prognostic factors were intraoperative blood loss (<400 vs. ≥400 ml, risk ratio 1.64; p=0.045) and CY (0 vs. 1, risk ratio 2.25; p=0.004). CONCLUSION: The control of intraoperative bleeding had a positive impact on the survival of patients receiving curative resection for Borrmann type IV gastric cancer.

DOI： 10.21873/anticanres.13967

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BACKGROUND: We investigated the clinical influence of anastomotic leak (AL) on esophageal cancer survival and recurrence after curative surgery. PATIENTS AND METHODS: This study included 122 patients who underwent curative surgery for esophageal cancer between 2008 and 2018. The patients were classified into those with AL and those without. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. RESULTS: AL was found in 44 out of the 122 patients (36.1%). The respective OS rates at 3 and 5 years after surgery were 43.9% and 40.2% in the AL group and 63.9% and 53.2% in the non-AL group, which were significantly different (p=0.0049). In contrast, the respective RFS rates at 3 and 5 years after surgery were 44.8% and 29.8%, and 44.9% and 42.4%, which were not significantly different (p=0.2306). A multivariate analysis showed that AL was a significant independent risk factor for both poorer OS and RFS in patients who underwent curative surgery for esophageal cancer. CONCLUSION: To improve survival of patients with esophageal cancer, the surgical procedure, perioperative care and surgical strategy must be carefully planned in order to prevent AL.

DOI： 10.21873/anticanres.13972

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PURPOSE: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. RESULTS: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. CONCLUSION: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

DOI： 10.1007/s00432-019-03087-8

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BACKGROUND/AIM: We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on esophageal cancer survival and recurrence after curative treatment. PATIENTS AND METHODS: This study included 122 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: An ACCI of 5 was regarded as the optimal critical point of classification considering the survival rates. The OS rates at 3 and 5 years after surgery were 64.2% and 54.4% in the low-ACCI group, respectively, and 42.3% and 29.2% in high-ACCI group, respectively (p=0.035). The RFS rates at 3 and 5 years after surgery were 50.2% and 43.6% in the low-ACCI group, respectively, and 28.5% and 21.3% in high-ACCI group, respectively (p=0.021). A multivariate analysis demonstrated that ACCI was a significant independent risk factor for both the OS and RFS. CONCLUSION: ACCI is a risk factor for survival in patients who undergo curative treatment for esophageal cancer. An effective plan for the perioperative care and surgical strategy should be developed according to ACCI.

DOI： 10.21873/invivo.12103

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BACKGROUND/AIM: We performed a retrospective multi-center cohort analysis to compare the outcomes of laparoscopic surgery vs. open surgery for obstructive colon cancer. PATIENTS AND METHODS: A total of 455 patients with colon cancer with ileus underwent surgery at Yokohama City University Hospital and four related institutions from April 2000 to March 2016. RESULTS: There were 414 cases in the open surgery group and 41 cases in the laparoscopic surgery group with no marked differences in the gender or age. The postoperative complication rate, according to the Clavien-Dindo classification, was lower in the laparoscopic group compared to the open surgery group. The postoperative hospital stay was 16 days in the open surgery group and 9 days in the laparoscopic surgery group (p=0.004). Among the various factors examined, the operation approach was identified as a statistically significant independent risk factor for postoperative complications (p=0.015). CONCLUSION: Preoperative treatment for colon cancer with ileus and elective laparoscopic surgery are thought to be useful for achieving curative treatment, avoiding colostomy, and shortening the length of hospital stay.

DOI： 10.21873/invivo.12105

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BACKGROUND/AIM: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. PATIENTS AND METHODS: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. RESULTS: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). CONCLUSION: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

DOI： 10.21873/invivo.11796

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BACKGROUND: Pancreatic cancer is a fatal disease with a poor prognosis. Pancreatic cancer is often unresectable at the time of diagnosis, so the analysis of risk factors in patients with indications for surgery is important. We investigated the impact of intraoperative blood loss (IBL) on survival and recurrence in patients with stage II/III pancreatic cancer after curative surgery. PATIENTS AND METHODS: This study included 76 patients who underwent curative surgery for stage II/III pancreatic cancer between 2007 and 2012. The risk factors for overall (OS) and recurrence-free (RFS) survival were identified. RESULTS: IBL of 1,000 ml was considered to be the optimal cut-off value for classification based on a receiver operating characteristic (ROC) curve analysis. The OS rates at 5 years after surgery in the groups with low and high IBL were 36.6% and 11.4%, respectively, which was a statistically significant difference (p=0.003). The RFS rates at 1 year after surgery were 49.8% and 24.6%, respectively, which was a significant difference (p=0.045). A multivariate analysis demonstrated that IBL was a significant independent risk factor for OS. CONCLUSION: IBL is an independent prognostic factor after curative resection of stage II/III pancreatic cancer. The reduction of bleeding during surgery is necessary to improve the results of pancreatic cancer surgery.

DOI： 10.21873/invivo.11931

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BACKGROUND/AIM: The present study aimed to identify risk factors for anastomosis leak (AL) after esophagectomy for esophageal cancer. PATIENTS AND METHODS: One-hundred twenty-two patients who underwent esophagectomy for esophageal cancer between 2008 and 2018 were included. The rate of AL was measured based on the definition of leak as adapted from the Surgical Infection Study Group. To identify the risk factors for AL, logistic regression analysis was used. RESULTS: AL was found in 44 of the 122 patients (36.1%). Among the factors examined, the lymph node dissection status (p=0.007) and preoperative serum albumin level (p=0.022) were significant independent risk factors for AL. The incidence of AL was 26.7% (20 of 75) among patients who received 2-field lymph node dissection and 51.1% (24 of 47) among those who received 3-field lymph node dissection. The incidence of AL was 29.9% (23 of 77) in the preoperative serum albumin levels ≥4.0 g/dl group and 46.7% (21 of 45) in the serum albumin levels <4.0 g/dl group. CONCLUSION: Lymph node dissection status and preoperative serum albumin levels were risk factors for AL in patients who received esophagectomy for esophageal cancer.

DOI： 10.21873/invivo.11849

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BACKGROUND/AIM: The aim of the present study was to evaluate the optimal number of harvested LNs (LNs) in patients who were LN metastasis-negative after curative esophagectomy for esophageal cancer. PATIENTS AND METHODS: Sixty-one patients who underwent curative surgery for esophageal cancer between 2005 and 2017 and diagnosed as lymph node metastasis-negative were included in this study. RESULTS: The 5-year overall survival rates were 27.8% for 0-20 harvested LNs, 35.7% for 21-30 harvested LNs, 79.4% for 31-40 harvested LNs, and 85.2% for ≥41 harvested LNs. Thirty harvested LNs was regarded as the optimal critical point of classification, considering the 5-year OS rate. The number of harvested LNs was selected as a significant prognostic factor in both univariate and multivariate analyses. The respective 3- and 5-year OS rates were 50.3% and 36.7% for <30 harvested LNs and 82.4% and 82.4% for ≥30 harvested LNs (p=0.003). CONCLUSION: Thirty or more harvested LNs was a significant prognostic factor in patients with metastasis-negative LNs after curative esophagectomy for esophageal cancer. Therefore, the number of harvested LNs might be useful for predicting the LN metastasis status in esophageal cancer.

DOI： 10.21873/invivo.12001

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BACKGROUND/AIM: Lymphovascular invasion (LVI) is recognized as a prognostic predictor of recurrence in certain carcinomas. According to current Japanese guidelines, however, in gastric cancer, LVI is not clinically useful information, except for predicting the curability of endoscopic resection. We clarified the clinical significance of LVI in gastric cancer and its correlation with disease prognosis. PATIENTS AND METHODS: A total of 2,090 cases of gastric cancer undergoing radical gastrectomy were enrolled. The correlation of LVI and other histopathological factors was evaluated with regards to patient prognosis. RESULTS: LVI(+) was noted in 894 cases. A multivariate analysis showed that pT, pN, and LVI were independent risk factors for patient prognosis. In pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVI(+) cases were lower than those in LVI(-) (60.9% vs. 76.7%, p=0.005). CONCLUSION: LVI in gastric cancer is an independent prognostic factor, and tends to worsen prognosis, especially in advanced cancers with lymph node metastases.

DOI： 10.21873/invivo.11942

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BACKGROUND/AIM: We investigated the clinical impact of the lymph node ratio (LNR) on overall survival (OS) and recurrence-free survival (RFS) in esophageal cancer patients who underwent curative surgery. PATIENTS AND METHODS: One hundred twenty patients who underwent curative surgery for esophageal cancer between 2005 and 2017 were included in this study. The LNR was defined as the ratio of the number of metastatic lymph nodes (LNs) to the total number of harvested LNs. RESULTS: A lymph node ratio of 10% was regarded as the optimal critical point for classification based on the overall survival rate. The 3-year and 5-year OS rates were 65.5% and 57.0%, respectively, in the LNR<10% group, and 11.8% and 0% in the LNR≥10% group; the difference was statistically significant (p<0.001). The 3-year and 5-year RFS rates were 52.6% and 44.6%, respectively, in the LNR<10% group, and 0% and 0% in the LNR>10% group; the difference was also statistically significant (p<0.001). When comparing the sites of first relapse, the incidence of distant lymph node metastasis in the LNR>10% group was significantly higher than that in the LNR<10% group. CONCLUSION: The LNR was a risk factor for both OS and RFS in patients who underwent curative surgery for esophageal cancer.

DOI： 10.21873/invivo.12012

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AIM: To compare long- and short-term outcomes of laparoscopic surgery with those of open surgery for patients with colorectal cancer and body mass index over 25 kg/m2 Patients and Methods: This multicentre, retrospective study analysed clinical records and identified 178 patients with body mass index over 25 kg/m2 who underwent surgery for colon and rectosigmoid cancer between 2000 and 2016. After applying propensity score matching, 96 patients were finally included. The primary outcome was the 3-year recurrence-free survival rate, and the secondary outcomes were short-term results during and after surgery. RESULTS: The 3-year recurrence-free survival rates were similar for the laparoscopic and open surgery groups. The laparoscopic surgery group had longer operative times but less blood loss and shorter periods of hospital stay. There were no differences in incidence of postoperative complications. CONCLUSION: Laparoscopic and open surgeries had similar long-term outcomes for obese patients. Laparoscopic surgery is an effective option for this population.

DOI： 10.21873/invivo.12011

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Transabdominal ultrasound is a promising technique to evaluate inflammatory bowel disease. Several studies have demonstrated a relationship between ultrasound findings and colonic inflammation. However, the applicability of transabdominal ultrasound in patients with ulcerative colitis (UC) has not been elucidated. The aim of this study was to clarify the relationship between the transabdominal ultrasound findings and endoscopic activity in patients with UC. METHODS: Patients with active and underwent transabdominal ultrasound and colonoscopy were enrolled in this retrospective single-center analysis. Blood flow in the bowel wall was evaluated by power Doppler ultrasound. Both the thickness and stratification of the bowel wall were assessed by B-mode ultrasound imaging. The endpoints were the correlations between the ultrasound appearances (i.e., blood flow, thickness, and stratification of the bowel wall) and endoscopic activity (endoscopic Mayo Score). RESULTS: There were 34 lesions in 26 patients evaluated. Blood flow and thickness of the bowel wall were positively significantly correlated with the endoscopic Mayo Scores (r=0.43, p=0.011 and r=0.503, p=0.002, respectively). According to the bowel stratification, the endoscopic Mayo Scores were significantly higher in unclear and diminished bowel wall stratifications than in the clear bowel wall stratifications (p<0.001 and p<0.001, respectively). When focusing on the endoscopic Mayo Scores of three lesions, blood flow was lower in ulcer lesions with a diameter of ≥10mm than in those with a diameter of <10mm. CONCLUSION: All transabdominal ultrasound findings of bowel blood flow, wall thickness, and wall stratification reflected colonic inflammation.

DOI： 10.11405/nisshoshi.117.695

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Kampo medicine or Japanese/Chinese traditional herbal medicine has long been used for the treatment of various diseases, mainly in Asian countries. In recent years, Asian investigators have attempted to clarify the mechanism and clinical efficacy of Kampo medicine. This review summarizes the background, current status, and future perspectives of Kampo medicine in the multimodal treatment of gastrointestinal cancer. Regarding the clinical effect of Kampo medicine on postoperative dysfunction after gastrointestinal surgery, several investigators have reported that Daikenchuto (TJ-100) had clinical efficacy after abdominal digestive surgery. The administration of TJ-100 during the immediate postoperative period after esophageal cancer surgery, gastric cancer surgery, and liver cancer surgery appeared to promote early recovery of the postoperative bowel function. Regarding Kampo medicine for chemotherapy-induced adverse effects in gastrointestinal cancer, promising results have been obtained for Hangeshashinto (TJ-14) and Goshajinkigan (TJ-107). The addition of TJ-14 might be associated with an improvement in the duration of chemotherapy-induced oral mucositis, and the addition of TJ-107 might be associated with an improvement in oxaliplatin-induced peripheral neurotoxicity. However, while several clinical trials have shown the positive results of Kampo medication for gastrointestinal cancer treatment, the clinical effects of such medicines have been limited. Further trials to investigate the clinical benefits of Kampo medicine are needed.

DOI： 10.7150/jca.46748

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BACKGROUND: The short- and long-term outcomes of gastrectomy in elderly patients with gastric cancer have not been fully evaluated. PATIENTS AND METHODS: Patients who underwent gastrectomy were classified into two groups: Non-elderly patients (<80 years old) and elderly patients (≥80 years old). The surgical morbidity, overall and cancer-specific survival in the two groups were compared. RESULTS: A total of 411 patients were evaluated. The rate of overall complication was 29.4% in the non-elderly and 32.4% in the elderly (p=0.699). In the elderly, the overall and cancer-specific survival rates at 5 years after surgery were inferior to those of the younger group (59.8% vs. 66.7%, p=0.103 and 67.9% vs. 78.2%, p=0.028, respectively). CONCLUSION: The short-term outcomes after gastrectomy were almost equal for the two groups in the present study. The prognosis was poor in elderly patients, especially those with advanced gastric cancer.

DOI： 10.21873/invivo.12090

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DOI： 10.21873/invivo.11848

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DOI： 10.4993/acrt.28.97

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BACKGROUND: The C-reactive protein (CRP)-to-serum albumin ratio is associated with a poor prognosis in patients with several cancers. The purpose of this study was to clarify the relationship between the preoperative CRP/Alb ratio and overall survival of pancreatic ductal adenocarcinoma (PDAC) in patients who received radical surgery and S-1 adjuvant chemotherapy. PATIENTS AND METHODS: We included 117 patients who underwent radical surgery with S-1 adjuvant chemotherapy. We constructed receiver operating characteristic curve (ROC curve) of the CRP/Alb ratio to determine the cut-off value. We analyzed the relationship among the CRP/Alb ratio, clinicopathological status, and survival. RESULTS: The optimal cut-off value of the CRP/Alb ratio was 0.036. All patients were divided into a high-ratio group (CRP/Alb ratio ≥0.036) and low-ratio group (CRP/Alb ratio <0.036). The 5-year overall survival (OS) rates in the high- and low-ratio groups were 22.5% and 36.4%, respectively (p=0.0089). The 5-year disease-free survival (DFS) rates in the high- and low-ratio groups were 12.5% and 22.1%, respectively (p=0.0097). The univariate and multivariate analyses of the OS showed that the pathological N factor and CRP/Alb ratio were independent factors of the survival. The univariate and multivariate analyses of the RFS showed that the pathological N factor, resection margin, and CRP/Alb ratio were independent factors of the survival. CONCLUSION: The preoperative CRP/Alb ratio is a strong prognostic factor for PDAC patients with undergo curative resection with S-1 adjuvant chemotherapy.

DOI： 10.21873/invivo.11780

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A 61-year-old man had a sudden severe abdominal pain and visited our hospital. He was diagnosed with intestinal perforation, given the peritoneal irritation symptoms, the thickening of the intestinal wall and free air as shown on enhanced abdominal computed tomography. He then underwent emergent surgery. A tumor with small perforation was found on the intestine about 15 cm distant from the terminal ileum. Partial resection of the ileum was performed. Microscopically, a type 2 tumor of 70×50mm in diameter, was observed in the resected intestine. The tumor was diagnosed as diffuse large B-cell lymphoma via immunochemical staining. He received 6courses of R-CHOP therapy after surgery without recurrence. A primary intestinal malignant lymphoma is easily perforated, which lead to poor prognosis of the patient. We report a case of perforated intestinal malignant lymphoma, which was induced to remission by multidisciplinary therapy.

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The patient was a 73-year-old man. A liver tumor was found in the posterior segment(S6)during the follow-up period post the interferon treatment for hepatitis C in September 1999. An S6 sub-segmentectomy was performed. The tumor was diagnosed as a moderately differentiated carcinoma, hepatocellular carcinoma(HCC)with pT2N0M0, pStage Ⅱ(UICC TNM 7th edition). The tumor recurred twice post-surgery. The recurrent tumors were treated with local therapies such as transcatheter arterial chemoembolization(TACE), percutaneous ethanol injection(PEI)and radiofrequency ablation(RFA). The third recurrence was found in the posterior segment(S7)in April 2009. RFA was unsuccessful because an appropriate puncture route could not be found. Then, a transdiaphragmatic RFA under thoracotomy was performed as an alternative treatment, which led to an optimal outcome. We report a case of HCC that could not be treated with percutaneous RFA but with a transdiaphragmatic RFA under thoracotomy.

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BACKGROUND/AIM: The KIAA1199 gene has been associated with cancer-cell proliferation, but its functions remain poorly studied. Here, we examined the clinical significance of the KIAA1199 mRNA levels in locally advanced gastric cancer (GC). Materials and Methods/Results: Using samples from 254 patients with stage II/III GC, we found significantly higher KIAA1199 levels in cancerous tissues compared to adjacent normal mucosa (ANM). There was no significant relationship between KIAA1199 expression and clinical features. Although overall survival rates (OSR) of patients, who underwent surgery did not correlate with KIAA1199 expression, patients who underwent adjuvant chemotherapy with S-1 and had high KIAA1199 levels displayed significantly lower OSR. KIAA1199 knock down (KIAA1199-KD) suppressed proliferation, invasiveness, and sensitivity of GC cells to 5-fluorouracil (5-FU). CONCLUSION: KIAA1199 expression appears to be a promising prognostic marker in patients with locally advanced GC, who underwent postoperative adjuvant chemotherapy with S-1. KIAA1199 may represent a novel target for GC pharmacotherapy.

DOI： 10.21873/anticanres.13872

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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We report a case of altered consciousness related to hyperammonemia due to FOLFIRI plus bevacizumab therapy in a patient with recurrent colorectal cancer and renal dysfunction.A 76-year-old man received third-line chemotherapy for left mediastinal lymph node metastasis.He complained of diarrhea on the evening of the same day, and mental confusion on day 3 of the first FOLFIRI therapy.He had a JCS of Ⅲ(200).The laboratory results revealed a marked hyperammonemia.5 - fluorouracil(5-FU)-induced hyperammonemia was diagnosed and the patient was ventilated and managed with branchedchain amino acid solutions, lactulose, and hemodialysis in the ICU.After hemodialysis, the blood ammonia level reduced to the normal limits, and the symptoms of encephalopathy resolved on the following day.He was discharged home on the 19th day of hospitalization.5 -FU-containing therapy should be carefully administered in patients with renal dysfunction.Herein, we report a case of 5-FU-induced hyperammonemia with literature considerations.

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Appendiceal mucinous neoplasm has a risk for pseudomyxoma peritonei caused by appendiceal perforation.It has been reported that laparoscopic surgery is more risky than open surgery.We investigated 4 patients who underwent laparoscopic surgery for appendiceal mucinous neoplasm.The median age was 69.5(49-85).There were 3 males and 1 female.Three cases of partial laparoscopic resection of the cecum and 1 case of ileocecal resection with lymph node dissection were performed. The pathology was low-grade mucinous neoplasm in all cases.The median hospital stay was 6 days, and there were no postoperative complications(CD Grade 3 or higher)or hospital death.As for long-term results, peritoneal pseudomyxoma developed in 1 case, which had already ruptured at the time of surgery.There were no recurrences in other cases.This result suggests that laparoscopic surgery for appendiceal mucinous neoplasm is safe with optimal selection of the procedure and a protective technique.

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Primary carcinoma of the vermiform appendix is a rare neoplasm, and its treatment strategy has not yet been established. We retrospectively analyzed 8 cases of primary carcinoma of the vermiform appendix from 2007 to 2017. Six cases were male and two were female, with a median age of 60.5 years. Ileocecal resection and right hemicolectomy were performed in 7 cases and 1 case, respectively. Regarding pathological staging, 5 cases were of pStage Ⅱ, 2 were of pStage Ⅲa, and 1 was of pStage Ⅳ. Three cases had recurrences after curative resection. The postoperative median overall survival time was 45 months. Three cases with a tumor diameter of 20mm were alive without any recurrence; however, 3 of 5 cases with a tumor diameter of B21mm had recurrences. Although only 1 of 3 cases with adjuvant chemotherapy(pStage Ⅲa case)had recurrence, 2 of 4 cases without adjuvant chemotherapy, including a pStage Ⅱ case, had recurrences. Early diagnosis, surgery, and adjuvant chemotherapy could improve the long-term outcomes of patients with primary carcinoma of the vermiform appendix.

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We report a long-surviving case of malignant peritoneal mesothelioma requiring 4 operations in 5 years. A 63-year-old man was diagnosed with gastrointestinal stromal tumor(GIST)that was excised for the first time in June 2011. The pathological diagnosis was malignant peritoneal mesothelioma. Thereafter, we excised recurrences of the tumor in the hepatic hilum in December 2011. Similar operations were performed in March 2012 and August 2015 because of tumors in the small bowel mesentery and the segment 8 of the liver. The pathological diagnosis was malignant peritoneal mesothelioma. It is an extremely rare variant of malignant peritoneal mesothelioma. There is no record of multiple excision of malignant peritoneal mesothelioma for recurrences. In this case, the cause of long survival was considered to be the excision of recurrent tumors.

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A 52-year-old man whose fecal occult blood test was positive was found to have type 2 sigmoid colon cancer by colonoscopy. On enhanced barium enema study, the cecum was in the pelvis, and the ascending colon was running medially in the abdomen. Enhanced CT scan of the abdomen revealed rotation of the superior mesenteric vein(SMV). We diagnosed the case as sigmoid colon cancer(cT3N0M0, StageⅡA)with non rotation-type intestinal malrotation, and performed laparoscopic surgery. We confirmed the small intestine to be located on the right side of the abdomen, the cecum to be located in the pelvis, and the ascending colon to be running medially in the abdomen. The ascending mesocolon was adherent to the right of the sigmoid mesocolon. Following dissections of the ascending mesocolon from the sigmoid mesocolon, we performed surgery via the inside approach as usual. We dissected the root of the inferior mesenteric artery(IMA), and the operation was completed. In laparoscopic surgery for colorectal cancer with intestinal malrotation, there are some reports that it could be performed safely if attention is paid to adhesion of the mesenteries and vascular variation in the course of preoperative imaging diagnosis. We report a case of laparoscopic surgery that could be safely performed for sigmoid colon cancer with non rotation-type intestinal malrotation.

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A 77-year-old woman was taking anticoagulant medication for pulmonary hypertension. Black stools were noted in August 2018. Close abdominal ultrasonography revealed a broad-based tumor at the base of the gallbladder. Lower endoscopy showed no obvious digestive tract hemorrhage but hemorrhage from a gallbladder tumor was suspected. The resected procedure was suspected for gallbladder cancer(cT2N0M0, cStageⅡ), but dizziness 5 days before operation. The patient complained of severe anemia, and underwent laparoscopic cholecystectomy for hemorrhage control. In the macroscopic examination of the specimens, tumorous lesions and blood clots were found adhered to the bottom of the gallbladder. The histopathological diagnosis was papillary adenocarcinoma.

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BACKGROUND: Laparoscopic surgery in patients with retroperitoneal fibrosis has been reported to be difficult due to mesenteric and retroperitoneal fibrotic thickening. Here, we report a case of laparoscopic surgery with IgG4-related disease. CASE PRESENTATION: A 60-year-old man with IgG4-related kidney disease and autoimmune pancreatitis was diagnosed with cecal cancer. Laparoscopic ileocecal resection was performed. Preoperative CT showed no evidence of retroperitoneal fibrosis but showed a localized fibro-inflammatory lesion between the retroperitoneum and mesentery in front of the right kidney due to interstitial nephritis. Intraoperative findings revealed focal adhesions in the duodenal front within the range consistent with CT findings. CONCLUSIONS: This report shows that the degree and extent of fibrosis were similar between preoperative CT and actual surgical findings. Thus, it is possible that tissue fibrosis in patients with IgG4-related disease could be predicted by preoperative CT.

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This case involved a 42-year-old woman who had no remarkable findings in terms of case history and family history. Upper gastrointestinal series performed during a medical examination revealed ulcerative lesions in the anterior wall of the stomach body. Upper gastrointestinal endoscopy was performed, and a submucosal tumor with a maximum diameter of 50mm accompanied by an ulcerative lesion was found in the anterior wall of the lower part of the stomach. She was diagnosed with a schwannoma based on endoscopic ultrasonography-guided fine needle aspiration, and we received consultation for surgical purpose. Surgery was performed with laparoscopic partial resection of the stomach and lymph nodes in the lesser curvature of the stomach. She was discharged on the 7th day after the surgery. The postoperative pathologic findings showed no nuclear fissure or atypia with a diagnosis of a schwannoma and no lymph node metastasis. Gastric schwannoma is a rare disease that arises from Schwann cells of the Auerbach's plexus of the gastric wall muscularis and comprises 0.1-0.2% of all stomach tumors. Preoperative diagnosis is often extremely difficult, and there are reports of malignancy. Treatments and surgical methods should be carefully considered. Herein, we encountered a case of a resected giant gastric schwannoma by laparoscopic surgery, which is reported with a literature review.

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Language：Japanese   Publisher：日本臨床外科学会  

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This is a case of a 76-year-old man who had no significant past medical or family history. In the current medical history, in November 2017, upper gastrointestinal endoscopy showed a semicircular protruding lesion in the posterior wall of the gastric antrum, and gastric cancer was diagnosed following biopsy. Endoscopic submucosal dissection(ESD)was performed in the same year for the treatment of gastric cancer(cT1aN0M0). Pathological findings after ESD treatment showed invasion into the submucosa requiring non-curative resection. For this reason, laparoscopic pylorus side gastrectomy(D1 dissection)and Billroth Ⅰ reconstruction were performed as additional procedures in March 2018. The patient was discharged on the 10th postoperative day and was followed-up on an outpatient basis. On the postoperative day 14, he was re-admitted with complaints of upper abdominal pain and exacerbation of inflammation. Medical treatment, such as antibiotic administration was followed, however, a high degree of inflammatory response, renal dysfunction, and occult blood in urine were observed. Because of suspicion of vasculitis-related nephritis, the case was diagnosed as anti-GBM antibody type rapid progressive nephritis. We came across a case of rapidly progressive glomerulonephritis after laparoscopic pylorus side gastrectomy performed for early gastric cancer, and hence, We will review the related literature.

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BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.

DOI： 10.21873/anticanres.13771

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Undifferentiated cancer of the small intestine has a poor prognosis and has rarely been reported.We report a case of undifferentiated intestinal carcinoma.A 55-year-old man presented with epigastralgia in December 2018. Blood test results showed a high degree of anemia.Contrast -enhanced abdominal CT showed a small intestinal tumor with a diffuse thickened wall along with multiple liver metastases.Capsule endoscopy revealed a bleeding tumor.It was diagnosed as carcinoma by transhepatic-ultrasound-guided core needle biopsy.Given the preoperative diagnosis of intestinal carcinoma, we resected the tumor along with a part of the small intestine and the enlarged lymph nodes.The pathological diagnosis was undifferentiated intestinal carcinoma.The patient was discharged on the 6th postoperative day after surgery.He was scheduled to receive postoperative chemotherapy.There was no evidence of undifferentiated intestinal carcinoma.Herein, we review case reports from the literature.

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DOI： 10.1007/s10151-019-02081-z

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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Perioperative oral/dental care has been introduced to cancer surgery patients as perioperative management using a multimodal approach. Several approaches were tested for managing perioperative oral/dental health care in this population. However, while the clinical impact of perioperative oral/dental care on patients with various types of malignancies has been evaluated, most previous studies have used and evaluated data obtained from relatively small sample sizes of fewer than 200 patients from individual institutions. Therefore, the recommendation of perioperative oral/dental care is controversial. Recent studies have shown that perioperative oral/dental care affects the cancer surgery outcomes. In addition, perioperative oral/dental care by dentistry professionals and the number of oral/dental care sessions have been shown to be important for this beneficial effect, even when patients were temporarily intubated. Further studies are, therefore, necessary to establish the optimal perioperative dental/oral care regiment and verify the beneficial effect of perioperative oral/dental care on cancer surgery outcomes. This review summarizes the background, current status, and future perspectives of perioperative oral/dental care for cancer surgery.

DOI： 10.21873/anticanres.13396

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PURPOSE: The benefits of laparoscopic surgery for colorectal cancer have been well established. Several randomized controlled trials have demonstrated similar oncological outcomes between laparoscopic and open surgery for colon cancer. However, whether or not laparoscopic surgery is acceptable in patients with clinical N2 colon cancer is unclear. Therefore, the present study aimed to evaluate the safety and oncological outcomes of laparoscopic surgery for clinical N2 colon cancer. METHODS: This retrospective study assessed a prospective database and identified 262 consecutive patients with clinical N2 colon cancer who underwent either laparoscopic or open primary resection between 2000 and 2016. After propensity-score matching, 162 patients were analyzed. The primary outcome of interest was the 3-year recurrence-free survival rate, and the secondary outcome of interest was the postoperative complication rate. RESULTS: The 3-year recurrence-free survival rate did not differ markedly between the laparoscopic and open surgery groups (77.4% vs. 76.5%, p = 0.620). In addition, the incidence of postoperative complications did not differ markedly between the laparoscopic and open surgery groups (16.6% vs. 24.0%, p = 0.317). CONCLUSIONS: Our findings suggest that laparoscopic surgery is safe and effective for clinical N2 colon cancer. Laparoscopic resection can be considered in patients diagnosed with clinical N2 colon cancer.

DOI： 10.1007/s00595-019-1762-z

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BACKGROUND/AIM: Postoperative pneumonia after esophageal cancer can lead to additional pain, prolonged hospital stay, and respiratory failure. These adverse events might lead to early recurrence and/or death. We investigated the influence of postoperative pneumonia on the esophageal cancer survival and recurrence after curative surgery. PATIENTS AND METHODS: This study included 122 patients who underwent curative surgery for esophageal cancer between 2008 and 2018. The patients were classified into: i) those with postoperative pneumonia (pneumonia group) and ii) those without postoperative pneumonia (non-pneumonia group). The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. The rate of postoperative pneumonia was measured by the revised Uniform Pneumonia Score. RESULTS: Postoperative complications were found in 34 of the 122 patients (27.9%). The OS rate at 5 years following surgery was 28.2% in the pneumonia group and 55.1% in the non-pneumonia group (p=0.006). The RFS rate at 5 years after surgery was 18.9% in the pneumonia group and 49.2% in the non-pneumonia group (p=0.061). A multivariate analysis showed that postoperative pneumonia was a significant independent risk factor for OS. CONCLUSION: The development of postoperative pneumonia was a risk factor for a decreased overall survival in patients who underwent curative surgery for esophageal cancer. The surgical procedure, perioperative care and surgical strategy should be carefully planned in order to avoid postoperative pneumonia.

DOI： 10.21873/anticanres.13392

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BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear. METHODS: We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more. RESULTS: One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien-Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group. CONCLUSION: This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.

DOI： 10.1007/s10120-018-0873-3

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PURPOSE: The favorable oncological impact of D3 lymph node dissection after colon cancer surgery has been described previously. However, D3 lymph node dissection is potentially more invasive than conventional D2 lymph node dissection. The oncological merit of D3 lymph node dissection in elderly patients with colon cancer remains unclear. This study aimed to clarify the oncological outcome after D3 lymph node dissection in patients with colon cancer aged > 75 years. METHODS: This is a retrospective cohort analysis using propensity matching method. The study was conducted at a university hospital and two community teaching hospitals in a large urban city. A total of 378 consecutive patients with pathological stage II and stage III colon cancer who underwent primary resection with either D2 or D3 lymph node dissection were retrospectively identified on a prospective database between 2000 and 2015. The primary and secondary outcomes of interests were recurrence-free survival and postoperative complication rate, respectively. RESULTS: After propensity matching, 232 patients were analyzed. The long-term findings showed that the elderly who underwent D3 lymph node dissection had significantly better recurrence-free survival than those who underwent D2 lymph node dissection (p = 0.01). The incidence of postoperative complication was almost similar between the two groups. CONCLUSIONS: D3 lymph node dissection provides better recurrence-free survival than D2 lymph node dissection after primary resection for elderly patients with pathological stage II and stage III colon cancer.

DOI： 10.1007/s00384-018-03233-7

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Language：Japanese   Publisher：(一社)日本外科学会  

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A 66-year-old woman diagnosed with advanced Stage Ⅳ gastric cancer(T4aN3M1[LYM])received RAM plus wPTX as third-line chemotherapy(ramucirumab 8mg/kg on the 1st and 15th day, paclitaxel 80mg/m2 on the 1st, 8th, and 15th day).After receiving 3 courses of this treatment, para-aortic lymphadenopathy had diminished but anemia had progressed because of tumor hemorrhage.Six weeks after the last administration of RAM, an open distal gastrectomy with D1 plus lymph node dissection and Billroth Ⅰ reconstruction was performed.The patient was discharged on the 9th day after surgery without complications such as postoperative bleeding and delayed wound healing.RAM plus wPTX therapy was restarted 6 weeks after the operation.Postoperative late complication there is no adverse event including adenocarcinoma and continues the same therapy at present.The perioperative treatment under the use of angiogenesis inhibitor has risk of postoperative bleeding and wound healing delay and includes surgery timing of treatment may be difficult.In our case, surgery was performed 6 weeks after the final administration of RAM.

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In a 65-year-old woman, anemia was observed during outpatient follow-up after right lung cancer surgery, and upper gastrointestinal endoscopy was performed for examination.Gastrointestinal endoscopy revealed a Type 2 tumor on the small curvature in the middle part of the stomach, and she was diagnosed with gastric cancer.Distal gastrectomy with D2 lymph node dissection and BillrothⅠ reconstruction was performed for the gastric cancer.There were no postoperative complications, and she was discharged on the ninth day after surgery.The pathological diagnosis was gastric cancer, ML, Less, Type 2, 67×55×15 mm, muc>sig>por, pT4a(SE)N2M0, fStage ⅢB.S -1 adjuvant chemotherapy was administered, but then discontinued in the second course due to the development of adverse events.Reflux symptoms appeared after the surgery, and her dietary intake was poor.Her body weight and serum albumin level at 3 and 5 months after surgery were 51 kg and 52.5 kg, respectively, and 3.2 g/dL and 2.7 g/dL, respectively.Because there was no improvement in the reflux symptom, oral administration of acotiamide hydrochloride was initiated 7 months after the surgery.After initiating oral intake of acotiamide hydrochloride, her dietary intake improved, and her body weight and serum albumin level at 11 and 15 months after surgery were 54 kg and 57 kg, respectively, and 3.0 g/dL and 2.7 g/dL, respectively.Peritoneal recurrence was observed 23 months after surgery, and her oral intake decreased, but the recurrence of reflux symptoms was not observed.Acotiamide hydrochloride could be an option for the treatment of reflux symptoms after gastrectomy.

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BACKGROUND: Body weight, especially lean body mass, significantly decreases after gastrectomy. Postoperative surgical complications are a major risk factor for changes in body weight and body composition after gastrectomy. However, the influence of postoperative surgical complications after gastrectomy on body weight and body composition changes remains unclear. PATIENTS AND METHODS: This retrospective study examined patients who underwent curative surgery for gastric cancer between May 2010 and February 2017. Their body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery, and at 1 week, 1 month and 3 months after surgery. Patients were classified as those with surgical complications and those without. RESULTS: Eight hundred and eighty-eight patients (156 in the group with complications and 732 in the group without) were entered in the present study. When comparing the two groups, the patients' background and surgical factors significantly differed, while the pathological findings were similar. The body weight losses at 1 week, 1 month, and 3 months after surgery were 3.8%, 7.0%, and 10.4%, respectively, in those with complications, and 3.3%, 5.6%, and 6.8%, respectively, in the group without, with p-values of 0.001, 0.002, and 0.001, respectively. The corresponding lean body mass losses were 3.7%, 6.5%, and 6.8%, and 3.2%, 4.2%, and 3.5%, respectively, with p-values of 0.001, 0.001, and 0.001, respectively. CONCLUSION: Decreases in body weight and lean body mass after gastrectomy were more serious in the patients with surgical complications than in those without. To maintain body weight and lean body mass in patients with surgical complications, additional care or treatments are needed.

DOI： 10.21873/anticanres.13215

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 63-year-old man was admitted to our hospital for examination and treatment of a pancreatic head tumor detected at a nearby hospital. After CT, EUS-FNA, and PET-CT, he was diagnosed with unresectable pancreatic cancer with liver metastasis. After 9 courses of gemcitabine and nab-paclitaxel therapy, the primary tumor was dramatically reduced in size and the liver metastasis had disappeared. He underwent subtotal stomach-preserving pancreaticoduodenectomy. The postoperative diagnosis according to the General Rules of the Study of Pancreatic Cancer(7th edition)was Ph, TS1(15mm), adenosquamous carcinoma, ypT3, ypRP1, ypPL1, R0, ypN0(0/29), M0, CY0, ypStage ⅡA. The histological response was Grade 2. The patient remains alive without recurrence 5 months after surgical resection.

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BACKGROUND: Several retrospective studies have shown that bone disorders occur after gastric cancer surgery. This study was designed to prospectively evaluate the changes in bone metabolism after gastrectomy for gastric cancer. METHODS: We prospectively enrolled 39 men with early gastric cancer who underwent gastrectomy. We excluded women to avoid the effects of menopause. We employed dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) of the lumbar spine. DEXA was performed before and 1 and 2 years after surgery. The serum levels of alkaline phosphatase (ALP), 1,25-dihydroxy vitamin D [1,25(OH)2VD], 25-hydroxy vitamin D [25(OH)VD], and estradiol were measured before surgery and every 3 months until 2 years after surgery. RESULTS: DEXA revealed that BMD significantly decreased by 0.036 ± 0.033 g/cm2 12 months after gastrectomy (P < 0.001) and by 0.046 ± 0.040 g/cm2 24 months after gastrectomy (P < 0.001). The serum ALP level significantly increased by 38.31 ± 103.8 IU/L 24 months after surgery (P = 0.013). The serum 25(OH)VD level significantly decreased by 4.88 ± 6.42 ng/ml 24 months after surgery (P < 0.001), whereas the serum 1,25(OH)2VD levels were consistently in the normal range. The serum estradiol level significantly increased by 2.94 ± 7.49 pg/ml 12 months after gastrectomy (P = 0.035). A lower preoperative body mass index (BMI) significantly correlated with the reduction in BMD 12 months after surgery; the correlation coefficient was 0.37 (P = 0.025). CONCLUSIONS: This study showed that a significant decrease in BMD was observed for up to 24 months after gastrectomy, not only 12 months.

DOI： 10.1007/s10120-018-0835-9

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Language：Japanese   Publisher：横浜市立大学医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01499&link_issn=&doc_id=20190711360004&doc_link_id=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F1793&url=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F1793&type=%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

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Aims: We previously demonstrated that a loss of lean body mass loss at one month after gastrectomy was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether or not lean body mass loss after gastrectomy leads to a poor survival through poor compliance to adjuvant chemotherapy with S-1. Methods: The recurrence free survival (RFS) overall survival (OS) and were examined in 115 patients who underwent curative gastrectomy and were pathologically diagnosed with stage II or III gastric cancer and who received postoperative adjuvant chemotherapy with S-1 between May 2011 and September 2016. Results: The median follow-up period was 40.6 months. The RFS rates at 5 years after surgery were 57.8% in the lean body mass loss ≥5% group and 73.5% in the lean body mass loss <5% group. The univariate and multivariate analyses for the disease free survival (RFS) demonstrated that a lean body mass loss >5% was a significant risk factor. The OS rates at 5 years after surgery were 72.0% in the lean body mass loss ≥5% group and 77.3% in the lean body mass loss <5% group. The OS was slightly worse in the lean body mass loss ≥5% group than in the lean body mass loss <5% group (p=0.2062). Conclusions: The lean body mass loss at one month, which is closely associated with poor S-1 compliance, was an important risk factor for the RFS. A prospective cohort study is necessary to confirm whether or not the lean body mass loss affects the gastric cancer survival.

DOI： 10.7150/jca.30697

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Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.

DOI： 10.7150/jca.34741

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BACKGROUND/AIM: We investigated the impact of Beppu's nomogram on colorectal liver metastasis in patients receiving perioperative chemotherapy and/or targeted therapy. PATIENTS AND METHODS: This study included 43 patients who underwent primary hepatic resection for colorectal liver metastasis at the Kanagawa Cancer Center from June 2006 to March 2011. The patients were classified as having a Beppu's nomogram score ≤9 (low-risk group) or ≥10 (high-risk group). The risk factors for the disease-free survival (DFS) were identified. RESULTS: The respective DFS rates at 1, 2, and 3 years after surgery were 72.0%, 43.3%, and 17.3% in the low-risk group and 27.8%, 16.7%, and 8.3% in the high-risk group, the difference being significant (p=0.009). The multivariate analysis showed that Beppu's nomogram score ≥10 was a significant independent risk factor for the DFS. CONCLUSION: Beppu's nomogram score was an independent prognostic factor for colorectal liver metastasis in patients receiving perioperative chemotherapy and/or targeted therapy. Thus, Beppu's nomogram might be a useful tool for predicting the risk of recurrence after hepatectomy, even in the era of newly-developed chemotherapy.

DOI： 10.21873/invivo.11603

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Background: The aim of this study was to determine whether or not the short- and long-term outcomes were affected by the age-adjusted Charlson comorbidity index (ACCI) in patients who underwent curative resection for gastric cancer. Methods: The patients were retrospectively selected from among the medical records of consecutive patients who underwent curative gastrectomy with nodal dissection for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015. Results: A total of 2254 patients were eligible for inclusion in the present study. One thousand six hundred fifty-six patients had an ACCI of <6 points (ACCI low group), while 598 had a score of ≥6 points (ACCI high group). The median age (p<0.001) and American Society of Anesthesiologists physical status (ASA-PS) score (p<0.001) of the ACCI high group were higher in comparison to the ACCI low group. The incidence of surgical complications in the ACCI high group was significantly higher than that in the ACCI low group (12.0% vs. 7.2%, p<0.001). Univariate and multivariate analyses demonstrated that an ACCI high classification was a significant risk factor for postoperative complications. In addition, the 5-year OS rates of the ACCI low and ACCI high groups were 85.4% and 74.1%, respectively. The difference was statistically significant (p<0.001). The univariate and multivariate analyses demonstrated that an ACCI high classification was a significant prognostic factor for OS. Conclusions: Our results support that a high ACCI value is an independent risk factor for the short- and long-term outcomes of patients with gastric cancer. To improve the survival of patients with gastric cancer, it is necessary to carefully plan the perioperative care and the surgical strategy according to the ACCI.

DOI： 10.7150/jca.35465

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PJD Publications Ltd  

DOI： 10.4993/acrt.27.52

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PJD Publications Ltd  

DOI： 10.4993/acrt.27.31

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Body weight, especially lean body mass, significantly decreases after gastrectomy for gastric cancer due to surgical invasion, reduced food intake, and reduced mobility, which can reduce the quality of life and induce associated toxicity or reduce compliance with adjuvant chemotherapy. Such risks can be particularly high in elderly patients with gastric cancer. However, whether or not changes in the weight and body composition differ between elderly and non-elderly patients remains unclear. PATIENTS AND METHODS: This retrospective study examined patients who underwent curative surgery for gastric cancer between May 2010 and February 2017. Body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery, at 1 week after surgery, and at 1 and at 3 months after surgery. Patients were classified as elderly (≥80 years) or non-elderly (<80 years). RESULTS: Eight-hundred and eighty-eight patients (84 elderly and 804 non-elderly) were entered into the present study. Patient background, surgical and clinicopathological factors, and surgical complications did not significantly differ between the two groups. Body weight loss at 1 week, and at 1 and 3 months after surgery, defined as the decrease from the preoperative value, were -2.8%, -6.5%, and -9.0%, respectively, in the elderly and -3.5%, -6.0%, and -8.1%, respectively, in the non-elderly patients (p=0.111, 0.125, and 0.153, respectively). The corresponding losses of lean body mass were -2.6%, -6.0%, and -6.4%, respectively, in the elderly and -3.5%, -4.9%, and -4.7%, respectively, in the non-elderly patients, with p-values of 0.056, 0.036, and 0.029, respectively. CONCLUSION: Decreases in lean body mass after gastrectomy were greater in elderly than in non-elderly patients. In order to maintain lean body mass among elderly patients, additional care and treatments are needed.

DOI： 10.21873/invivo.11463

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Background: The predictive roles of secreted protein acidic and rich in cysteine (SPARC) in pancreatic ductal adenocarcinoma (PDAC) patients after curative resection have not been clarified. We investigated the correlations between the SPARC expression and the postoperative prognosis. Methods: We retrospectively analyzed the clinical data from consecutive patients who underwent curative resection for pancreatic cancer in our institution from 2005 to 2014. Stromal SPARC expression was analyzed by immunohistochemistry on tumor tissue microarrays (TMAs) from the patients. Results: A total of 179 patients were enrolled to this study. The median follow-up period of the present study was 62.1 months. Seventy patients had positive SPARC expression (39.1%). There were no significant differences between the positive SPARC-positive group and the SPARC-negative group. In the survival analysis, there was a significant difference between the SPARC-positive and SPARC-negative groups in the 5-year overall survival (OS) rates after surgery, which were 8.1% and 19.8%, respectively (p=0.0316). A univariate analysis showed that the SPARC expression, size of tumor, lymph node metastasis, and residual tumor were possible prognostic factors. A multivariate analysis showed that the SPARC expression (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.017-2.051), lymph node metastasis (HR: 2.019, 95% CI: 1.318-3.091), and residual tumor (HR: 1.648, 95% CI: 1.132-2.401) were independent prognostic factors. Conclusions: The stromal SPARC expression in resectable pancreatic cancer patients might be useful as a prognostic marker.

DOI： 10.7150/jca.28660

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Background: In previous our phase III study to compare perioperative standard diet with or without Eicosapentaenoic acid (EPA)-enriched oral nutritional supplement (EPA-ON), additional EPA-ON did not contribute to prevent body weight loss after total gastrectomy. This report clarified whether EPA-ON could prevent loss of lean body mass (LBM) after total gastrectomy, a key secondary endpoint, in our phase III trial. Methods: This phase III study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA-ON body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either Standard-diet group or EPA-ON group by a centralized dynamic method. Standard-diet group was given no additional nutritional supplementation perioperatively (standard diet), while EPA-ON group was given an EPA-enriched supplement (ProSure®, Abbott Japan, Tokyo, Japan) in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. For both groups, patients underwent total gastrectomy with Roux-en Y reconstruction. Results: A total of 123 patients (Group A: 60, Group B: 63) were analyzed in the study. All background factors were well balanced between the both groups. Median loss of LBM was 6.74% (range -3.91% to 20.27%) in the Standard-diet group and 6.89% (range -5.11% to 20.04%) in the EPA-ON group at 1 month after surgery and was 8.59% (range -4.40% to 20.27%) in the Standard-diet group and 7.77% (range -5.57% to 23.35%) in the EPA-ON group at 3 months after surgery, which was not significantly different at the both (p=0.794 and p=0.393, respectively). Conclusions: The perioperative EPA-ON could not be recommended to prevent loss of LBM after total gastrectomy.

DOI： 10.7150/jca.29632

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BACKGROUND: This study investigated the impact of postoperative C-reactive protein (CRP) level on survival in patients with esophageal cancer who received perioperative steroid therapy and enhanced recovery after surgery (ERAS) care. PATIENTS AND METHODS: Overall, 115 patients were retrospectively reviewed. The patients were classified into those with a high CRP level (≥4.0 mg/dl) on postoperative day 4 and those with low CRP level (<4.0 mg/dl). The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: The OS and RFS rates at 5 years after surgery were significantly low in patients with high CRP level on postoperative day 4. The multivariate analysis demonstrated that high CRP level on postoperative day 4 was a significant independent risk factor for OS and RFS. CONCLUSION: The present results suggest that the postoperative CRP level can be a prognosticator in patients with esophageal cancer who have received perioperative steroid therapy and ERAS care.

DOI： 10.21873/invivo.11515

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BACKGROUND/AIM: The purpose of this study was to reveal the safety and efficacy of additional surgical resection (ASR) for high-risk T1 colorectal cancer (CRC) after endoscopic resection (ER). PATIENTS AND METHODS: We retrospectively analyzed 191 patients with high-risk T1 CRC after ER. RESULTS: The ASR was performed in 176 (92.1%) patients and 15 (7.9%) rejected ASR. All patients that underwent ASR experienced R0 resection; laparoscopic surgery was performed in 159 (90.3%) patients. Clavien-Dindo complications ≥grade II occurred in 33 patients (18.8%). Anastomotic leakage (8.5%) and ileus (5.7%) were the most frequent complications. The anus function was preserved in all patients. Metastatic lymph node was detected in 21 (11.9%) patients. There were no deaths or relapses in patients with ASR. One patient without ASR (6.7%) had a lymph node recurrence. CONCLUSION: ASR was safe and effective and is recommended for high-risk T1 CRC patients after ER. A satisfactory long-term outcome can be achieved.

DOI： 10.21873/invivo.11596

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Language：Japanese   Publishing type：Research paper (scientific journal)  

This is a case of a 70-year-old man. Two courses of docetaxel/cisplatin/S-1 combination therapy were administered after clinical trial registration with diagnosis of Stage Ⅳ gastric cancer(ypT3N3aM1). In June 2014, gastrectomy and splenectomy were performed. Postoperative S-1 adjuvant chemotherapy was administered; however, in September 2014, aorticl ymph node metastasis was diagnosed as recurrent. After recurrence, irinotecan/cisplatin therapy was administered. In February 2015, recurrent lymph node metastasis increased, and chemotherapy was changed to paclitaxel. In May 2015, numbness (Grade 2)of the fingers was observed, and treatment was changed to oxaliplatin/S-1. In February 2016, storage of ascites became remarkable; therefore, chemotherapy was discontinued as per policy. After that, we continued outpatient visit and observed increased recurrent lymph node metastasis on image evaluation; however, as the patient's general condition was good, chemotherapy was restarted. Ramucirumab/paclitaxel therapy started in February 2017. During the course of treatment, neutropenia(Grade 2)was observed as an adverse event, but therapy continuation was possible without loss of ramucirumab only with loss of paclitaxel. Thereafter, the recurrence of lymph node metastasis was reduced, and the ascites accumulation decreased. Until now, 1 year after the start of ramucirumab/paclitaxel therapy, the patient still visits the outpa- tient clinic.

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BACKGROUND: The factors associated with the survival and prognosis of peritoneal cytology (CY)-positive pancreatic cancer patients who undergo curative resection followed by adjuvant chemotherapy have not been established. PATIENTS AND METHODS: Both overall survival (OS) and recurrence-free survival (RFS) were examined in 23 peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy between 2005 and 2015. RESULTS: When the length of OS was evaluated using a log-rank test, significant differences were observed in the number of metastatic lymph nodes. In addition, univariate and multivariate analyses demonstrated that the number of metastatic lymph nodes was a significant independent risk factor for OS and a marginally significant risk factor for RFS. The 3-year OS rate was 20.2% in patients with ≤8 metastatic lymph nodes, and it was 0% in those with the ≥9 metastatic lymph nodes (P = 0.017). The 3-year RFS rate was 6.3% in patients with ≤8 metastatic lymph nodes, whereas it was 0% in those with ≥9 metastatic lymph nodes (P = 0.062). CONCLUSIONS: The number of metastatic lymph nodes is the most important prognostic factor for OS and RFS in peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy. To improve the survival of these patients, it is necessary to establish optimal treatments.

DOI： 10.4103/0973-1482.194927

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 74-year-old woman was found to have a hepatic mass based on CT findings. She was diagnosed as having cecum cancer, and it was difficult to distinguish whether the hepatic mass was liver metastasis or biliary cystadenocarcinoma. We proceeded with the surgery for cecum cancer, and laparoscopic ileocecal resection with D3 lymph node dissection was performed. The histopathological diagnosis was mucinous adenocarcinoma, and the pathological stage was T3N2H1P0M1a, Stage IV. After the surgery, her CEA level was elevated, and we diagnosed the hepatic mass as a liver metastasis. A CapeOX plus bevacizumab regimen was administered but was discontinued for 2 courses due to the development of adverse effects and her decision. Gd-EOB-DTPA-enhanced MRI revealed a multilocular and lobulated mass, which was a low-intensity area in T1WI and high-intensity area in T2WI, and the mass had no significant contrast effects. These images were unspecific for liver metastasis of colorectal cancer, and we performed segmental 6 hepatectomy for diagnosis and curative surgery. A histopathological diagnosis of liver metastasis of cecum cancer was made. Here, we report a case of liver metastasis of colorectal cancer that was undifferentiated from biliary cystadenocarcinoma.

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A 59-year-old woman was diagnosed with advanced gastric cancer with para-aortic and Virchow's lymph node metastases (L, Less, type 2, tub1, cT3N2H0P0M1[LYM: #16, Virchow's]). Four courses of S-1(80mg/m / 2, days 1-21)and CDDP(60mg/ m2, day 8)were administered. After the chemotherapy, CT showed that the primary tumor and para-aortic and Virchow's lymph nodes had reduced in size. The clinical stage was ycT3N1H0P0M0, stage III A. The patient underwent distalgastrectomy, D2 dissection, and sampling of the para-aortic lymph nodes(#16b1lat, #16a2int). The pathological diagnosis was L, less, type 1, por1/2, pT2N2H0P0M0CY0, pStage III B. The patient was treated with S-1(80mg/m2, days 1-28)as adjuvant chemotherapy. After 3 courses had been administered(6 months after the resection), swelling of a para-aortic lymph node (#16b1int)was detected using CT. Based on the diagnosis of recurrence in the lymph node, weekly paclitaxel(80mg/m2, days 1, 8, and 15)was administered. After receiving 9 courses of weekly paclitaxel, the swelling of the lymph node disappeared, and the response evaluation was complete response. She discontinued the chemotherapy 5 years and 9 months after the surgery. To date, she has survived more than 6 years after surgery without recurrence. We report a long-surviving patient with advanced gastric cancer with para-aortic lymph node metastasis who received combined modality therapy.

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BACKGROUND: We hypothesized that the relative proportion of tumor (PoT) at the luminal surface can predict gastric cancer (GC) patient survival. METHODS: We measured the luminal PoT in resection specimens from 231 GC patients with stage II/III disease who had surgery at the Kanagawa Cancer Center, Yokohama, Japan. Tissue microarrays were used to assess the extent of immune cell infiltration by CD45 immunohistochemistry. Results were related to histopathological features and patient overall survival (OS). RESULTS: PoT was significantly lower in diffuse-type (30%) compared to intestinal-type GC (41%), P = 0.03. Patients with low PoT intestinal-type GC survived significantly longer than patients with high PoT intestinal-type GC (5 years OS: 78% vs 47%, P = 0.0112). Low PoT was an independent favorable prognostic factor in multivariate analysis in intestinal-type GC. Low PoT was correlated with high content of CD45-positive immune cells (P = 0.035). There was no relationship between PoT and survival in diffuse-type GC. CONCLUSIONS: This is the first study to identify a subgroup of patients with stage II/III intestinal-type GC at high risk of recurrence by measuring PoT at the luminal surface. The relationship between PoT and immune cell content provides an initial insight into potential underlying biological mechanisms.

DOI： 10.1002/cam4.1744

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Language：English   Publisher：(一社)日本癌治療学会  

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We report of a long-surviving patient with retroperitoneal liposarcoma that required 6 surgeries in 16 years. A 62-year-old man was diagnosed with liposarcoma, which was first excised in 2001. Thereafter, we excised recurrences in the retroperitoneum with the left kidney in February 2004. We excised recurrences with the left half of the colon in November 2007 and February 2010 and recurrences with a part of the intestine in November 2014. This time, we excised recurrences under the right abdominal rectus muscle and near the left half of the colon. The pathological diagnosis was well-differentiated liposarcoma. There is currently no evidence of recurrence 16 years after the first recurrence excision. In this case, active excision of recurrences and identification of high-grade dedifferentiated-type liposarcomas were factors of long survival.

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Although chemotherapy is the standard treatment for unresectable advanced gastric cancer, its prognosis is poor and the median survival time is only around 10 months. With some literature consideration, we report that ovarian metastasis triggered the diagnosis of unresectable advanced gastric cancer with long-term survival through multidisciplinary treatment. This is the case of a 69-year-old woman, who was diagnosed with ovarian tumor and underwent right extracorporectomy and omentum resection in 2011. Pathological diagnosis suspected adenocarcinoma. In February 2012, EGD found a type 4 tumor in the upper portion of the pyloric area of the stomach. She was diagnosed with gastric cancer with Stage IV(T4aN0M1 [ovary])ovarian metastasis. Because the primary tumor was HER2 positive, XP plus HER therapy(capecitabine 1,000mg/m2 twice a day for 14 days, CDDP 80mg/m2 every 3 weeks on the first day, and trastuzumab 8 mg/kg every 3 weeks on the first day)was administered since March 2012. No metastasis was found in the imaging examination after 8 courses of chemotherapy, and we also confirmed the reduction of the primary tumor in the EGD. Based on the images, primary resection was already possible. In December 2012, after a diagnostic laparoscopy, total gastrectomy with D2 lymph node dissection was performed. Postoperative pathology was diagnosed as Stage IV(pT4aN0M1). To control postoperative micrometastasis, capecitabine therapy(1,000mg/m2 twice a day for 14 days)was administered for 12 months starting from February 2013. Then, recurrence and metastasis were not observed during follow-up. However, in January 2017, a circumstellar stenotic tumor was found in the rectum and was diagnosed as recurrence of peritoneal dissemination through images. In February 2017, artificial ostomy(in the sigmoid colon, double-mouth type)was made. Then, the patient underwent an outpatient chemotherapy, with hospital visits, and she survives.

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A 32-year-old woman with a history of undergoing upper gastrointestinal surgery was administered prednisolone for abortive Behçet's disease since 2015. In March 2017, upper gastrointestinal endoscopy revealed a 0-IIc type early stage gastric carcinoma at the posterior wall of the gastric antrum. The pathological diagnosis was signet-ring cell carcinoma. This gastric carcinoma was classified as cT1aN0M0; therefore, endoscopic submucosal dissection(ESD)was performed for the expanded indication lesion in April 2017. The pathological diagnosis after ESD indicated the need for non-curative resection; thus, laparoscopy-assisted distal gastrectomy and Billroth I anastomosis were performed in July 2017. A transient anastomotic structure was admitted after this surgery, but she was discharged from the hospital lighthearted. A preoperative important aspect was the careful examination of all intestinal tracts for ulcer lesions, and an intraoperative important aspect was hand-sewn anastomosis because using a metallic stapler conferred a high risk of ulcer lesions and suture failure. We encountered a case wherein laparoscopy-assisted distal gastrectomy was performed in a patient with abortive Behçet's disease, early stage gastric carcinoma, and a history of undergoing upper gastrointestinal surgery.

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AIM: This randomized phase III trial compared hepatic arterial infusion (HAI) chemotherapy with 5-fluorouracil (5-FU) followed by uracil/tegafur (UFT) and leucovorin (LV) versus UFT/LV alone for patients with curatively resected liver metastases from colorectal cancer (CRC). METHODS: The study was designed to include 280 patients to be randomized to receive either HAI with 5-FU followed by UFT/LV (Arm A) or UFT/LV alone (Arm B) to assess whether HAI chemotherapy improved disease-free survival (DFS). RESULTS: Forty-four patients were randomized. Three-year DFS was relatively worse in the experimental arm although this difference was not statistically significant (43.5% in Arm A vs. 58% in Arm B; hazard ratio [HR], 1.304; P = 0.534). The experimental arm also tended to have a worse 3-year overall survival rate (80.2% in Arm A vs. 85.2% in Arm B; HR, 2.255; P = 0.192). There was no significant difference in the frequency of Grade 3 or higher toxicities between the two arms. CONCLUSION: Although this study was limited by a small sample size after early study termination, our analysis found that HAI with 5-FU followed by UFT/LV did not improve the DFS of patients with curatively resected liver metastases from CRC compared with UFT/LV alone. The future studies are necessary to evaluate the survival benefit of HAI in combination with newer systemic chemotherapeutic agents for patients with resectable liver metastases from CRC.

DOI： 10.4103/0973-1482.179188

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BACKGROUNDS: In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294). METHODS: HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety. RESULTS: Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6-5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0-17.7) and ORR was 8/30 (26.7%) (95% CI 14.2-44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%). CONCLUSIONS: XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1. TRIAL REGISTRATION: NCT01412294.

DOI： 10.1007/s10120-018-0815-0

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BACKGROUND: It remains controversial whether coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) should be optimized to treat coronary artery disease in patients on chronic hemodialysis (HD). Recently, further refinement of drug-eluting stents, such as the everolimus-eluting stent (EES), has led to marked development in this field. We compared long-term clinical outcomes after CABG versus PCI with EES implantation in patients on chronic HD. PATIENTS AND METHODS: We compared 138 patients undergoing CABG and 187 patients treated with EES implantation. The endpoint was major adverse cardiac events (MACE) as a composite outcome, including any revascularization, nonfatal myocardial infarction, or mortality. To reduce the selection bias for the two procedures, propensity score-matching was performed. RESULTS: During the follow-up period (43 months), 95 (29.2%) MACEs, including 43 (13.2%) revascularizations, 14 (4.3%) nonfatal myocardial infarctions, and 63 (19.4%) deaths, occurred. The freedom rate from MACE and mortality at 5 years were comparable between groups (69.7 vs. 66.7%, P=0.82 and 75.0 vs. 80.6%, P=0.10, respectively); however, those from revascularization at 5 years was higher in the CABG group than the EES group (89.4 vs. 81.0%, P=0.030). In propensity score-matched patients (n=92), the freedom rate from revascularization at 5 years was still higher in the CABG group than in the EES group (93.4 vs. 79.1%, P=0.013). Similarly, the freedom rates from MACE and mortality were comparable (70.0 vs. 66.3%, P=0.69 and 73.8 vs. 79.7%, P=0.30, respectively). CONCLUSION: Even in the second-generation drug-eluting stent era, CABG is still superior for preventing revascularization in patients on chronic HD. However, PCI with EES implantation might not have disadvantages compared with CABG in terms of MACE.

DOI： 10.1097/MCA.0000000000000628

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PURPOSE: This study assessed whether our enhanced recovery after surgery (ERAS) program for distal pancreatectomy (DP) is safe and feasible. PATIENTS AND METHODS: The subjects were patients who underwent consecutive DP between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization, and 30-day readmission rate. Our ERAS program included 12 elements (4 preoperative elements, 3 intraoperative elements, and 5 postoperative elements). RESULTS: A total of 44 patients were studied. The overall incidence of morbidity was 29.5%, the incidence of mortality was 0%, and the incidence of readmission was 0%. Four preoperative elements and 3 intraoperative elements seemed feasible. Among the 5 postoperative elements, 4 elements seemed feasible, accounting 90%< performance rate however the early removal of catheters and drain seemed not feasible. The median postoperative hospital stay was 14 days (range: 8-39 days). The median postoperative hospital stay was 13 days (range: 8-27 days) in patients without postoperative complications while the median postoperative hospital stay was 26 days (range: 14-39 days) in patients with postoperative complications. CONCLUSION: This study results suggested that our ERAS program is safe and feasible in patients who undergo DP. However, achieving compliance on the postoperative element, especially the removal of catcher and drain, was more challenging.

DOI： 10.4103/0973-1482.183186

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BACKGROUND: Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP. PATIENTS AND METHODS: Eligible patients were randomised to receive either S-1 40 mg/m2 for 21 days plus cisplatin 60 mg/m2 (q5w) or capecitabine 1000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety. RESULTS: In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments. CONCLUSIONS: XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP. CLINICAL TRIAL REGISTRATION: NCT00140624.

DOI： 10.1016/j.ejca.2018.06.026

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DOI： 10.4993/ACRT.26.82

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DOI： 10.4993/acrt.26.95

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INTRODUCTION: We describe an easy technique to connect the anvil and center rod of the EEA™ OrVil™. MATERIALS AND SURGICAL TECHNIQUE: The bulb tip of EEA OrVil was orally inserted slowly until the valve tip reached the esophageal stump. The surgeon inserted forceps while grasping the anvil from the right abdomen trocar. The circular stapler (EEA XL) was inserted via the cut-off stump of the lifted jejunum or remnant stomach through the intraumbilical incision. Then, the circular stapler was held with the shaft convex. When the automated stapler and center rod were confirmed to be completely aligned, the anvil and the main unit were connected, and the device was fired. DISCUSSION: Although we only reversed the direction of the circular stapler's shaft, this method improved the ease of the operation.

DOI： 10.1111/ases.12446

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BACKGROUND/AIM: The present study investigated the impact of the lymph node ratio (LNR) on survival and recurrence in patients with pancreatic cancer after curative surgery followed by adjuvant chemotherapy. PATIENTS AND METHODS: This study included 189 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A lymph node ratio of 0.1 was considered to be the optimal cut-off point for classification based on the 3-year and 5-year survival rates. The OS rates at three and five years after surgery were 34.4% and 28.2% in the LNR <0.1 group, respectively, and 23.1% and 5.8% in the LNR ≥0.1 group, which amounted to a statistically significant difference (p=0.003). The RFS rates at one and three years after surgery were 26.6% and 20.5% in the LNR <0.1 group, respectively, and 8.0% and 0% in the LNR ≥0.1 group, which was a significant difference (p=0.001). A multivariate analysis demonstrated that the LNR was a significant independent risk factor for both the OS and RFS. CONCLUSION: The LNR was a risk factor for overall survival in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. It is necessary to develop strategies to effectively utilize the lymph node metastasis status.

DOI： 10.21873/anticanres.12801

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BACKGROUND: Body weight loss (BWL) is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. The risk factors for severe BWL after gastrectomy remain unclear. METHODS: The present study retrospectively examined patients who underwent curative gastrectomy for gastric cancer between January 2012 and June 2014 at Kanagawa Cancer Center. All patients received perioperative care based on the enhanced recovery after surgery protocol. The %BWL value was calculated based on the percentage of body weight at 1 month after surgery in comparison to the preoperative body weight. Severe BWL was defined as %BWL > 10%. The risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses. RESULTS: There were 278 patients examined. The median age of the patients was 68 years. The operative procedures included total gastrectomy [n=97; open (n=61) and laparoscopic {n=36)] and distal gastrectomy (n=181). Surgical complications of grade ≥ 2 (as defined by the Clavien-Dindo classification) were observed in 37 patients, these included: pancreatic fistula (n=9), anastomotic leakage (n=5), and abdominal abscess (n=3). There were no cases of surgery-associated mortality. Both univariate and multivariate logistic analyses demonstrated that surgical complications, and total gastrectomy were significant risk factors for severe BWL. CONCLUSIONS: Surgical complications and total gastrectomy were identified as being significant risk factors for severe BWL in the 1st month after gastrectomy. To maintain body weight after gastrectomy, physicians should pay careful attention to patients who undergo total gastrectomy and those who develop surgical complications.

DOI： 10.1016/j.asjsur.2017.02.005

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BACKGROUND: This study was designed to investigate whether postoperative infectious complications (ICs) are a risk factor for the prognosis in esophageal cancer patients who receive neoadjuvant chemotherapy by stratifying the response to neoadjuvant chemotherapy. METHODS: The present study retrospectively examined patients who received neoadjuvant chemotherapy followed by esophagectomy between January 2011 and September 2015. Risk factors for overall survival (OS) were examined by Cox proportional hazard analyses. Pathological responders to neoadjuvant chemotherapy were defined as those with a tumor disappearance of more than one-third of the initial tumor. Postoperative ICs were defined using the Clavien-Dindo classification. RESULTS: Of the 111 patients examined, 45 (40.5%) developed postoperative ICs. A pathological response to neoadjuvant chemotherapy was observed in 54 (48.6%) patients. The multivariate analysis demonstrated that postoperative ICs were a significant independent risk factor for the OS (hazard ratio [HR] 2.359; 95% confidence interval [CI] 1.057-5.263, p = 0.036). In the subset analysis, postoperative ICs were a marginally significant independent risk factor for OS in the nonresponders (HR 2.862; 95% CI 0.942-8.696, p = 0.063) but not in the responders (HR 0.867; 95% CI 0.122-6.153, p = 0.886). CONCLUSIONS: These results suggested that the negative survival impact of postoperative ICs can be canceled out in esophageal cancer patients who respond to neoadjuvant chemotherapy.

DOI： 10.1245/s10434-018-6504-8

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BACKGROUND: Most previous reports to analyze risk factors for peritoneal recurrence in patients with colon cancer have been observational studies of a population-based cohort. OBJECTIVE: This study aimed to determine the risk factors for peritoneal recurrence in patients with stage II to III colon cancer who underwent curative resection. DESIGN: This was a pooled analysis using a combined database obtained from 3 large phase III randomized trials (N = 3714). SETTINGS: Individual patient data were collected from the Japanese Foundation for Multidisciplinary Treatment of Cancer clinical trials 7, 15, and 33, which evaluated the benefits of postoperative 5-fluorouracil-based adjuvant therapies in patients with locally advanced colorectal cancer. PATIENTS: We included patients who had stage II to III colon cancer and underwent curative resection with over D2 lymph node dissection. MAIN OUTCOME MEASURES: Main outcomes measured were risk factors for peritoneal recurrence without other organ metastasis after curative surgery. RESULTS: Peritoneal recurrence occurred in 2.3% (86/3714) of all patients undergoing curative resection. Mean duration from operation to peritoneal recurrence was 17.0 ± 10.3 months. Of these patients with peritoneal recurrence, 29 patients (34%) had recurrence in ≥1 other organ. Multivariate analysis showed that age (≥60 y: HR = 0.531; p = 0.0182), pathological T4 (HR = 3.802; p < 0.0001), lymph node involvement (HR = 3.491; p = 0.0002), and lymphadenectomy (D2: HR = 1.801; p = 0.0356) were independent predictors of peritoneal recurrence. The overall survival was lower in patients who developed peritoneal recurrence than in those with other recurrence (HR = 1.594; p = 0.002). LIMITATIONS: The regimens of adjuvant chemotherapy were limited to oral 5-fluorouracil. CONCLUSIONS: Our findings clarified the risk factors for peritoneal recurrence in patients who underwent curative resection for colon cancer. See Video Abstract at http://links.lww.com/DCR/A609.

DOI： 10.1097/DCR.0000000000001002

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BACKGROUND/AIM: Previous studies have shown that laparoscopic colorectal cancer surgery is highly safe and effective compared to laparotomy. However, whether laparoscopic colorectal cancer surgery can be safely performed in patients with severe comorbidities remains unclear. The aim of this study was to evaluate the safety of laparoscopic colorectal cancer surgery in patients with severe comorbidities. PATIENTS AND METHODS: A total of 82 consecutive patients with colorectal cancer who underwent laparoscopic surgery were retrospectively divided into two groups according to whether they had severe comorbidity (50 patients) or non-severe comorbidity (32 patients). An age-adjusted Charlson comorbidity index of ≥6 was defined as severe comorbidity. RESULTS: Operative time, blood loss, and rate of conversion to laparotomy did not differ between the groups. Postoperative complications and the length of the postoperative hospital stay also did not differ significantly between the groups. CONCLUSION: Laparoscopic colorectal cancer surgery is feasible and safe, even in patients with severe comorbidities.

DOI： 10.21873/anticanres.12659

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The prevalence of colorectal cancer in the elderly population is increasing; therefore, surgical interventions with a risk of potential complications are more frequently performed. The aim of the present study was to elucidate whether sarcopenia has a clinical impact on short-term outcomes, such as morbidity and hospital stay after surgery, in elderly patients with colorectal cancer. A total of 82 elderly patients undergoing colectomy for colorectal cancer between January 2011 and December 2015 in our institute were included in the study, and skeletal muscle mass was measured as total psoas area at the level of the third lumbar vertebra (L3) using enhanced computed tomography scans. The patients were divided into two subgroups, namely those with and those without sarcopenia, based on median skeletal muscle mass in men and women, and the association with complications was analyzed. A total of 40 patients (48.8%) were diagnosed with sarcopenia. The patients with sarcopenia exhibited a significantly higher incidence of total complications (55 vs. 31.0%, P=0.028) and longer hospital stay (25.9±21.2 vs. 18.2±8.5 days, P=0.039). The multivariate logistic analysis revealed that sarcopenia was an independent risk factor for postoperative surgical complications. The short-term outcomes, such as postoperative surgical complications and hospital stay, were affected by preoperative sarcopenia in elderly colorectal cancer patients. To improve the short-term outcomes of such patients, it is necessary to carefully plan the surgical procedure, perioperative care and the surgical strategy using preoperative sarcopenia assessment.

DOI： 10.3892/mco.2018.1607

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The standard treatment for stage II/III gastric cancer is surgical resection followed by adjuvant chemotherapy with fluoropyrimidine anticancer agents, including S-1. The protein, secreted protein, acidic and cysteine-rich (SPARC), promotes angiogenesis, and the proliferation and migration of cancer cells. The present study evaluated the significance of expression of the SPARC gene in patients with stage II/III gastric cancer who had undergone surgical resection and adjuvant chemotherapy with S-1. In the present study, reverse transcription-quantitative polymerase chain reaction was performed in order to quantify mRNA expression levels of SPARC in cancer tissues and adjacent normal mucosa obtained from 134 patients with stage II/III gastric cancer who had undergone surgical resection followed by adjuvant chemotherapy with S-1. The mRNA expression level of SPARC was significantly higher in cancer tissues than in adjacent normal mucosa (P=0.0012). Additionally, the 5-year overall survival rate was significantly poorer in patients with high SPARC gene expression than in those with low expression (P<0.0001). Furthermore, multivariate analysis indicated that high SPARC mRNA expression was a significant predictor of poorer survival in patients with stage II/III gastric cancer who had undergone surgical resection and adjuvant chemotherapy with S-1 (HR, 5.347; P<0.0001). Therefore, high expression of the SPARC gene may be a useful predictor of outcomes in patients with stage II/III gastric cancer, who have received treatment involving surgical resection and adjuvant chemotherapy with S-1.

DOI： 10.3892/ol.2018.8248

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BACKGROUND: The therapeutic efficacy of dissection of the splenic hilar lymph nodes (#10) has not been fully evaluated in locally advanced proximal gastric cancer (LAGC) invading the greater curvature of the stomach. METHODS: Patients with LAGC invading the greater curvature who underwent D2 total gastrectomy with splenectomy between January 2000 and May 2015 were retrospectively examined. The therapeutic value index was calculated by multiplying the metastatic rate of a station and the 5-year survival of patients with metastasis to that station; the metastatic rate and the index of each lymph node station were then compared. RESULTS: In total, 82 patients were eligible for the present study. The most frequent metastatic node was #3, followed by #1, #4d and #7, #2, #4sa and #10, and #4sb and #9. These lymph nodes had a metastatic rate of more than 10%. The node station with the highest index was #3, followed by #7, #4d, #1, #4sb, #4sa, #2, and #9. The index of #10 was lower, but exceeded those of #8a and #11p. CONCLUSIONS: The metastatic rate of #10 was relatively high at 13%, and the therapeutic value index was as high as those of other suprapancreatic nodes. D2 dissection for proximal cancer located in the greater curvature should include removal of node #10.

DOI： 10.1007/s10120-017-0775-9

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BACKGROUND: Although colorectal cancer comprises several histological subtypes, the influences of histological subtypes on disease progression and treatment responses remain controversial. OBJECTIVE: We sought to evaluate the prognostic relevance of mucinous and poorly differentiated histological subtypes of colorectal cancer by the propensity score weighting analysis of prospectively collected data from multi-institute phase III trials. DESIGN: Independent patient data analysis of a pooled database from 3 phase III trials was performed. SETTINGS: An integrated database of 3 multicenter prospective clinical trials (the Japanese Foundation for Multidisciplinary Treatment of Cancer 7, 15, and 33) was the source of study data. INTERVENTIONS: Surgery alone or postoperative adjuvant chemotherapy was offered in patients with resectable colorectal cancer. MAIN OUTCOME MEASURES: To balance essential variables more strictly for the comparison analyses, propensity score weighting was conducted with the use of a multinomial logistic regression model. We evaluated the clinical signatures of mucinous and poorly differentiated subtypes with regard to postoperative survival, recurrence, and chemosensitivity. RESULTS: Of 5489 patients, 136 (2.5%) and 155 (2.8%) were pathologically diagnosed with poorly differentiated and mucinous subtypes. The poorly differentiated subtypes were associated with a poorer prognosis than the "others" group (HR, 1.69; 95% CI, 1.00-2.87; p = 0.051), particularly in the patient subgroup of adjuvant chemotherapy (HR, 2.16). Although the mucinous subtype had a marginal prognostic impact among patients with stage I to III colorectal cancer (HR, 1.33; 95% CI, 0.90-1.96), it was found to be an independent prognostic factor in the subpopulation of patients with stage II disease, being associated with a higher prevalence of peritoneal recurrence. LIMITATIONS: The treatment regimens of postoperative chemotherapy are now somewhat outdated. CONCLUSIONS: Both mucinous and poorly differentiated subtypes have distinct clinical characteristics. Patients with the mucinous subtype require special attention during follow-up, even for stage II disease, because of the risk of peritoneal or local recurrence. See Video Abstract at http://links.lww.com/DCR/A531.

DOI： 10.1097/DCR.0000000000001022

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BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer may prevent the loss of body weight and lean body mass resulting from reduced surgical stress in comparison to open distal gastrectomy (ODG). A multicenter phase III trial conducted by the Japan Clinical Oncology Group (JCOG0912 trial) was performed to confirm the non-inferiority of LADG to ODG for stage I gastric cancer in terms of relapse-free survival. METHODS: This study was performed as a single-institution exploratory analysis using the data of the patients from our hospital who were enrolled in the JCOG0912 phase III trial. Body weight and lean body mass were evaluated using a bioelectrical impedance analyzer within 1 week before and at 1 week, 1 month, and 3 months after surgery. RESULTS: One-hundred six patients were randomized to undergo ODG (54 patients) or LADG (51 patients). Body weight loss at 1 week, 1 month, and 3 months was -3.0%, -4.9%, and -5.4%, respectively, in the ODG group and -2.7%, -4.3%, and -5.7%, respectively, in the LADG group; the differences were not statistically significant (p = 0.330, 0.166, and 0.656, respectively). Lean body mass loss at 1 week, 1 month, and 3 months was -2.8%, -4.1%, and -2.3%, respectively, in the ODG group and -2.7%, -2.9%, and -3.0%, respectively, in the LADG group; the differences were not statistically significant (p = 0.610, 0.413, and 0.925, respectively). CONCLUSIONS: The laparoscopic approach did not attenuate the loss of body weight and lean body mass in comparison to patients who underwent open distal gastrectomy for gastric cancer.

DOI： 10.1007/s10120-017-0735-4

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BACKGROUND: Body temperatures in elderly patients undergoing a pancreaticoduodenectomy(PD)for treatment of pancreatic cancer have not been fully evaluated. We aimed to compare body temperature during a PD between elderly(75 years old)and non-elderly patients. METHODS: This retrospective study included patients who underwent PD between April 2012 and April 2014 at the Kanasgawa Cancer Center. Patients were categorized into 2 groups: elderly patients(≥75 years of age: group A)and non-elderly patients(<75 years of age: group B). Body temperatures were compared between the groups. RESULTS: We evaluated 58 patients-14 were classified into group A, and 44 into group B. Preoperative clinicopathological outcomes demonstrated no significant differences between patients. A comparison of body temperatures between the groups showed 36.3°C(before surgery)/36.1°C(at 1 hr)/36.3°C(at 2 hr)/36.7°C(at 3 hr)/36.8°C(at 4 hr)/37.1°C(at 5 hr)/37.4°C(at 6 hr)in group A compared to 36.2°C(before surgery)/36.2°C(at 1 hr)/36.4°C(at 2 hr)/36.6°C(at 3 hr)/ 36.9°C(at 4 hr)/37.0°C(at 5 hr)/37.3°C(at 6 hr)in group B. Results did not significantly differ between the groups. CONCLUSIONS: Our study suggests that body temperature is not affected by a patient's age.

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BACKGROUND/AIM: To evaluate the safety of laparoscopic colorectal cancer surgery for patients with severe comorbidities. PATIENTS AND METHODS: A total of 203 consecutive patients with severe comorbidities who underwent resection for colorectal cancer were retrospectively divided into laparoscopic and open primary resection groups. An age-adjusted Charlson comorbidity index ≥6 was considered as severe comorbidity. RESULTS: Blood loss (31 g vs. 207 g, p<0.01) and total postoperative complications (10.0% vs. 27.5%, p<0.01) in the laparoscopic group were significantly decreased compared to the open group. Incidence of postoperative ileus (0.0% vs. 7.2%, p=0.06) and length of postoperative hospital stay (11 days vs. 14 days, p=0.08) in the laparoscopic group were improved, though not significantly, compared to the open group. CONCLUSION: Laparoscopic resection for patients with severe comorbidities is safe, and is associated with a lower rate of overall operative complications compared to open surgery.

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The standard therapy for Stage IV gastric cancer is chemotherapy. It is not certain, but conversion surgery is expected to be effective. We report the cases of 3 patients who achieved long-term survival after conversion surgery. Case 1 was of a 59- year-old woman. The tumor was classified as L-Less Post, Type 2, tub1, cT3N2M1(#16a2lat), Stage IV. Then, we initiated S-1 plus cisplatin and the LN achieved PRafter 4 courses. We performed distal gastrectomy with D2 lymph node dissection in February 2011. It was classified as ypT2N2 and the primary lesion was histologically classified as Grade 1a. Case 2 was of a 74- year-old man. The tumor was classified as UM-Less Ant, Type 3, por1, cT3N2H0P1CY1, Stage IV. Then, we initiated docetaxel plus cisplatin plus S-1 and the primary tumor achieved PRafter 6 courses. There were no new tumors and we conducted a laparoscopic examination. After the decision of P0CY0, we performed total gastrectomy with D2 lymph node dissection in April 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 2. Case 3 was of a 64-yearold woman. The tumor was classified as UM-Less, Type 3, por1, cT3N2H1M0(liver), Stage IV. Then, we initiated capecitabin plus cisplatin and liver metastasis achieved PRafter 6 courses. We performed total gastrectomy with D2 lymph node dissection in July 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 1b. All postoperative chemotherapy courses were of only S-1. In case 1, the para aortic LN exhibited recurrence 6 months postoperatively. We initiated weekly paclitaxel as second-line therapy. It achieved CRafter 6 courses, and the same trend was maintained. In cases 2 and 3, no therapy was administered after 8 S-1 courses, but no recurrences occurred. All patients survived after 62-77 months postoperatively. A new clinical trial is needed to prove the improvement in prognosis for Stage IV gastric cancer after conversion surgery.

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DOI： 10.4993/acrt.26.17

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We report a long-surviving case of retroperitoneal liposarcoma requiring 6 operations in 24 years. A 56-year-old female was diagnosed with liposarcoma and it was resected for the first time in 1991. The pathological diagnosis was well-differentiated liposarcoma. Thereafter, we resected recurrences in the retroperitoneum in July 2008, with the left half of the colon in June 2011. Then, we resected the pancreatic tails, spleen, accessory spleen, left adrenal gland, left kidney, and part of the diaphragm in October 2012, and part of the diaphragm, descending colon, and jejunum in October 2014. At this time, there were growing recurrences removed from the pancreatic tails. There is no evidence of recurrence after 24 years after the first resection. In this case, it was thought that the factor correlated with long survival was actively resecting recurrences and recognizing high-grade dedifferentiated type liposarcoma at an early stage.

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BACKGROUND: We conducted a randomized phase III trial comparing tegafur/uracil (UFT) and Polysaccharide-K (PSK) to surgery alone in curatively resected stage II rectal cancer patients. METHODS: Patients were randomly assigned to receive either UFT and PSK or surgery alone in a 1:1 ratio with a minimization method to balance the treatment allocation. The primary end point of this study was the disease-free survival (DFS). The secondary end point was the overall survival (OS). RESULTS: From October 2011 to February 2013, 111 patients were registered from 62 institutions. The study was prematurely closed due to poor accrual after reaching 20% of its goal. The patients' characteristics were similar between the UFT and PSK group and the surgery-alone group. The DFS rate was 76.0% at 3 years and 65.1% at 5 years in the UFT and PSK arm and 84.0% at 3 years and 77.2% at 5 years in the surgery-alone arm. The DFS was slightly worse in the UFT + PSK arm than in the surgery-alone arm, but the difference did not reach statistical significance (log rank p = 0.102). The OS rate was 100% at 3 years and 97.9% at 5 years in the UFT + PSK arm, while that was 100% at 3 years and 93.4% at 5 years in the surgery-alone arm. The OS was similar in the UFT + PSK arm and surgery-alone arm (p = 0.533). CONCLUSION: The present study suggests that UFT and PSK are not attractive candidates to advance to the next phase III study because the DFS was slightly worse in the UFT and PSK arm than in the surgery-alone arm.

DOI： 10.1007/s00280-017-3466-7

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OBJECTIVE: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). BACKGROUND: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. METHODS: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status. Results were compared between primGC and LNmet and related to clinicopathological data including survival. RESULTS: A total of 150 (63%) primGC had either RTK or DSS amplification. DSS coamplification was more frequent than RTK coamplification in primGC and LNmets. Moreover, 70 (30%) GC showed a disconcordant RTK and/or DSS gene copy number status between primGC and LNmet, most common was negative conversion for DSS genes (n=40 GC). The presence of RTK amplification in primGC was related to poorer survival in univariate analysis (P=0.04). CONCLUSIONS: This is the first and most comprehensive study in gastric cancer investigating the concordance between gene copy number status of targetable RTKs and downstream signaling oncogenes in primGC and LNmets. Future studies need to establish whether the relative high frequency of RTK and DSS coamplification and/or the relative high rate of negative conversion in LNmet can potentially explain recent failures of RTK targeted therapy in gastric cancer patients.

DOI： 10.1097/SLA.0000000000002042

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BACKGROUND/AIM: Laparoscopy-assisted total gastrectomy (LATG) for gastric cancer may prevent the loss of body weight or lean body mass after surgery due to its reduced surgical stress compared with open total gastrectomy (OTG). PATIENTS AND METHODS: A total of 303 patients were examined in this study. All patients received the same perioperative care via fast-track surgery. The body weight and composition were evaluated using a bioelectrical impedance analyzer within 1 week before and at 1 week, 1 month, and 3 months after surgery. RESULTS: Two hundred and eight patients received OTG, and 95 received LATG. Although the clinical T factor and N factor were significantly different between these two groups, other clinical factors were similar. The respective body weight loss (1 week/1 month/3 months) was -4.7%/-8.0%/-11.9% in the OTG group and -4.7%/-8.2%/-11.6% in the LATG group, that were not significantly different between the two groups at any time point of measurement (p=0.698/0.528/0.534, respectively). The respective lean body mass loss (1 week/1 month/3 months) was -4.2%/-6.4%/-7.4% in the OTG group and -4.0%/-5.8%/-6.2% in the LATG group, that were not significantly different between the groups (p=0.503/0.588/0.946, respectively). CONCLUSION: The body composition changes were similar between the OTG and LATG groups using the same perioperative care of fast-track surgery. Adopting a laparoscopic approach would not help in reducing loss of body weight or lean body mass after gastric cancer surgery.

DOI： 10.21873/invivo.11408

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Yokohama City University  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PJD Publications Ltd  

DOI： 10.4993/acrt.26.46

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Background: The current pooled analysis evaluated the efficacy of Hangeshashinto (TJ-14) in the prevention and/or treatment of chemotherapy-induced oral mucositis (COM) in gastric cancer and colorectal cancer using two prospective, multi-institutional, randomized, double-blind, placebo-controlled phase II trials. Patients and Methods: HANGESHA-G and HANGESHA-C randomly assigned patients with gastric cancer or colorectal cancer who developed moderate to severe COM (grade ≥1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for four to six weeks, according to the chemotherapy regimen, from the start of their next course of chemotherapy. The primary endpoint was the incidence of grade ≥2 COM in the protocol treatment course, and the secondary endpoints were the time to disappearance of COM and the incidence of adverse events. Results: The pooled population included 181 patients. The incidence of grade ≥2 COM in the TJ-14 group was 55.7% (49 patients), while that in the placebo group was 53.8% (50 patients); there was no significant difference between the two groups (p=0.796). The median time to remission of grade ≥2 COM to grade <1 was 8 days in the TJ-14 group and 15 days in the placebo group (p= 0.072). The hazard ratio was 1.54 [1.02 to 2.31] in favor of TJ-14. Treatment with TJ-14 was associated with marginally significant reduction in the duration of severe grade ≥2 COM in comparison to patients receiving placebo indicating the effect of TJ-14 in reducing the severity of COM. Conclusion: The present-pooled analysis showed that TJ-14 had a treatment effect in gastric cancer and colorectal cancer patients with COM in comparison to a placebo. Further phase III studies with a larger sample size are needed to clarify the protective effects of TJ-14 against COM.

DOI： 10.7150/jca.24733

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BACKGROUND: Serum C-reactive protein (CRP) level can be an indicator of the early stage of infectious complications. However, its utility in advanced esophageal cancer patients who receive radical esophagectomy with two- or three-field lymph node dissection with perioperative steroid therapy and enhanced recovery after surgery (ERAS) care is unclear. METHODS: The present study retrospectively examined 117 consecutive esophageal cancer patients who received neoadjuvant chemotherapy followed by radical esophagectomy. All patients received perioperative steroid therapy and ERAS care. The utility of the CRP value in the early detection of serious infectious complications (SICs) was evaluated based on the area under the receiver operating characteristic curve (AUC). Univariate and multivariate logistic regression analyses were performed to identify the risk factors for SICs. RESULTS: SICs were observed in 20 patients (17.1%). The CRP level on postoperative day (POD) 4 had superior diagnostic accuracy for SICs (AUC 0.778). The cut-off value for CRP was determined to be 4.0 mg/dl. A multivariate analysis identified CRP ≥ 4.0 mg/dl on POD 4 (odds ratio, 18.600; 95% confidence interval [CI], 4.610-75.200) and three-field lymph node dissection (odds ratio, 7.950; 95% CI, 1.900-33.400) as independent predictive factors. CONCLUSIONS: CRP value on POD 4 may be useful for predicting SICs in esophageal cancer patients who receive radical esophagectomy with perioperative steroid therapy and ERAS care. This result may encourage the performance of imaging studies to detect the focus and thereby lead to the early medical and/or surgical intervention to improve short-term outcomes.

DOI： 10.1186/s12885-017-3831-2

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BACKGROUND: Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). MATERIALS AND METHODS: We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. RESULTS: The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan-Meier curves for OS and DFS in the external validation dataset. CONCLUSIONS: We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset.

DOI： 10.18632/oncotarget.21845

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D2 gastrectomy is now the globally accepted surgical standard for locally advanced gastric cancer. However, since 2000, different evidence has emerged regarding the efficacy of adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy for locally advanced gastric cancer. This review summarizes the background, current status, and future perspectives of adjuvant therapy for locally advanced gastric cancer. The Intergroup 0116 study was the first to show the significant overall survival benefits of adjuvant (chemoradiation) therapy for gastric cancer. The second study was the MAGIC trial, which showed the efficacy of perioperative adjuvant chemotherapy. Although the findings from the Intergroup 0116 study and the MAGIC trial were positive, recent studies, such as the ARTIST and EORTC 40954 studies, found no survival benefit for patients who had undergone D2 gastrectomy for gastric cancer. Regarding the adjuvant chemotherapy strategy, two pivotal phase III trials: the ACTS-GC and the CLASSIC, demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. However, more intensive chemotherapy is necessary to improve the survival rate. Several studies have analyzed the effectiveness of molecular-targeted therapy against metastatic gastric or gastroesophageal junction carcinoma. Further studies should focus on the survival benefit of more-intensive adjuvant therapy with D2 resection, or with concurrent molecular-targeted therapy.

DOI： 10.1007/s00595-017-1493-y

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The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer.

DOI： 10.1002/cam4.1208

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 63-year-old man underwent a laparoscopic partial gastrectomy for GIST on September, 2001. Three years and 2 months after the gastrectomy, an abdominal CT showed multiple recurrences in S5 and S6 in the liver and peritoneum. After 4 months from the start of imatinib treatment(400mg/day), peritoneal tumors disappeared and the patient maintained stable disease by imatinib treatment for 8 years. However, on December, 2012, an abdominal CT scan revealed the regrowth of the tumor in S6 in the liver, and PET-CT showed focal progression of only the S6 lesion. Although the lesion was resectable, the patient did not request surgical intervention. So, we initiated sunitinib treatment(50mg/day), and the residual liver metastasis has been well controlled with favorable response of sunitinib for 4 years without severe side effects.

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A 65-year-old female received distal gastrectomy for gastric cancer.The pathological diagnosis was well differentiated adenocarcinoma(tub1), type 2, pT3, ly: 1, v: 1, N0, H0, P0, M0, CY0, pStage II A.She had been observed without adjuvant chemotherapy.Five years after the resection, umbilical tumor and intraperitoneal nodules were detected by computed tomography. Needle biopsy cytology of umbilical tumor revealed metastasis from gastric cancer.Based on the diagnosis of umbilical metastasis and peritoneal dissemination, S-1(80mg/m / 2, day 1-21)and CDDP(60mg/m2, day 8)were administered for 7 courses.Because of diarrhea(Grade 3), chemotherapy was changed to paclitaxel(80mg/m2, day 1, 8, 15).To date, the patient has undergone 33 courses of paclitaxel.The response evaluation is complete response and no other metastases are detected.She has survived more than 3 years from recurrence of gastric cancer.We report a long-surviving case of umbilical metastasis from post operative gastric cancer with chemotherapy.

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A 53-year-old man underwentdistal gastrectomy with Roux-en-Y(R-Y)reconstruction for gastric cancer. An R-Y anastomosis was performed usinga 21mm circular stapler. Five years postoperatively, he visited our hospital with anorexia. An abdominal computed tomography scan showed dilatation of the afferent loop. He was diagnosed with afferent loop syndrome due to R-Y anastomotic stenosis that resulted in poor oral intake and malnutrition. A U-shaped bend created by an adhesion caused a bowel obstruction of the Y-anastomotic site for which the patient underwent R-Y loop reconstruction with an aboral pouch usinga 60mm linear stapler. He has been well without postoperative complaints. Here, we report a case of R-Y loop reconstruction with an aboral pouch for afferent loop obstruction complicated by stenosis of the Y-anastomotic site after distal gastrectomy.

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The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

DOI： 10.3892/mco.2017.1357

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BACKGROUND: Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival. METHODS: Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors. RESULTS: The median OS was 22.3 months (95% confidence interval 18.7-31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0-N3a (pN0-N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0-N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007). CONCLUSIONS: The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

DOI： 10.1007/s10147-017-1128-8

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 72-year-old woman was referred to our hospital due to an abdominal mass. Ultrasound sonography and computed tomography revealed liver tumors in liver segments 2 and 3. The preoperative diagnosis was hepatocellular carcinoma. The patient underwent an extended left lobectomy. Histological examination of resected specimens revealed that the tumors were hepatic leiomyosarcoma. We report our experience of this hepatic leiomyosarcoma, along with the literature on this tumor type.

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The short- and long-term outcomes of colorectomy for colorectal adenocarcinoma have not been fully evaluated in elderly patients. The present retrospective study investigated patients who underwent curative surgery for colorectal cancer at the Department of Surgery, Yokohama City University (Yokohoma, Japan). The patients were categorized into two groups: Elderly patients (70-79 years of age; group A) and extremely elderly patients (≥80 years of age; group B). The rates of surgical morbidity, surgical mortality, overall survival (OS), and recurrence-free survival (RFS) in the two groups were compared. A total of 191 patients were evaluated in the current study. Of these, 137 patients were included in group A, and 54 were included in group B. With the exception of the American Society of Anesthesiology physical status score, there were no significant differences in the preoperative clinicopathological outcomes of the two groups. The overall complication rates in groups A and B were 12.4 and 16.7%, respectively, and did not differ to a statistically significant extent (P=0.440). In addition, surgical mortality was not observed in either group. The 5-year OS and RFS rates were similar between the group A and B patients (75.6 vs. 76.9%; P=0.5537; and 71.9 vs. 62.2%; P=0.192, respectively). The short-term outcomes and long-term survival following colorectomy for colorectal adenocarcinoma among patients in the 70-79 years of age group, and those who were ≥80 in the current study were almost equal. Thus, it is not necessary to avoid colorectomy for colorectal adenocarcinoma in elderly patients simply because of their age.

DOI： 10.3892/mco.2017.1380

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

DOI： 10.1093/annonc/mdx236

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The predictive roles of dihydropyrimidine dehydrogenase (DPD) in patients who undergo curative resection and adjuvant chemotherapy with S-1, which is the oral 5-fluorouracil prodrug tegafur combined with oteracil and gimeracil, remain unclear. In the present study, the clinical data from 66 consecutive patients who underwent curative resection and received adjuvant chemotherapy with S-1 for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama City, Japan) from April 2005 to March 2014 were retrospectively analyzed. The association between the DPD status and the survival and clinicopathological features were investigated. Of the 66 patients, 34 patients exhibited positive DPD expression (51.5%). Although a significant increase in DPD expression in male patients was observed, no significant differences were identified for other clinicopathological parameters, including tumor factor or node factor, between the DPD-positive expression group and the DPD-negative expression group. The median follow-up period of the present study was 29.2 months. There was no significant difference in the 3-year overall survival (OS) rates following surgery, which were 12.6 and 14.5% in the DPD-positive and DPD-negative expression groups, respectively (P=0.352). However, in a subgroup analysis, a significant difference in the 3-year OS rates following surgery was noted, which were 58.9 and 14.5% in the DPD-high and DPD-low expression groups, respectively (P=0.019). The intratumoral DPD expression in curatively resected pancreatic cancer patients treated with S-1 adjuvant chemotherapy was identified to not be useful as a predictive marker, whereas the level of DPD expression is a potential predictive marker. The results of the present study require confirmation in another cohort or in a prospective multicenter study.

DOI： 10.3892/ol.2017.6295

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This study assessed the impact of postoperative complications on the colorectal cancer survival and recurrence after curative surgery using pooled individual patients' data from three large phase III randomized trials. In total, 5530 patients were included in this study. The patients were classified as those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for the overall survival (OS) and the disease-free survival (DFS) were analyzed. Postoperative complications were found in 861 (15.6%) of the 5530 patients. The OS and DFS rates at 5 years after surgery were 68.9% and 74.8%, respectively, in the C group and 75.8% and 82.2%, respectively, in the NC group, values that were significantly different between the two groups (P < 0.001). The multivariate analysis demonstrated that postoperative complications were a significant independent risk factor for the OS and DFS. Postoperative complications can worsen the colorectal cancer survival and risk of recurrence. Surgical morbidity must be considered as a stratification factor in future phase III trials evaluating the effects of adjuvant chemotherapy on colorectal cancer.

DOI： 10.1002/cam4.1126

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The predictive roles of human equilibrative nucleoside transporter 1 (hENT-1) in patients who undergo curative resection and adjuvant chemotherapy with gemcitabine alone have not been established. The present study retrospectively analyzed the clinical data from 101 consecutive patients who underwent curative resection and who received gemcitabine adjuvant chemotherapy for the treatment of pancreatic cancer at Kanagawa Cancer Center (Yokohama, Japan) between 2005 and 2014. The associations between the hENT-1 status and the survival and clinicopathological features of the patients were investigated. Of the 101 patients, 60 patients (59.4%) had high levels of hENT-1 expression. A significant association was observed between hENT-1 status and sex; however, for all the other clinicopathological parameters, including tumor and node stages, no differences were observed between the high and low hENT-1 expression groups. The median follow-up period of the present study was 67.3 months. Between the high and low hENT-1 expression groups, there was a statistically significant difference in the 5-year overall survival (OS) rates following surgery (20.6 and 8.9%, respectively; P=0.019). In addition, a significant difference was observed in the recurrence-free survival (RFS) rates at 5 years following surgery (P=0.049). hENT-1 status was one of the important predictive factors for OS and RFS in patients with pancreatic cancer who underwent curative resection followed by adjuvant chemotherapy with gemcitabine. Adjuvant chemotherapy with gemcitabine alone may be insufficient, particularly in patients with certain relevant risk factors.

DOI： 10.3892/ol.2017.6220

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AIMS: We previously demonstrated that body weight loss (BWL) at one month after gastrectomy, a common finding after surgery for gastric cancer, was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether BWL after gastrectomy leads to poor survival through poor compliance to adjuvant chemotherapy with S-1. METHODS: We conducted this follow-up study in the same cohort as our previous study. Overall survival (OS) and recurrence-free survival (RFS) were examined in 103 patients who underwent curative D2 surgery and were pathologically diagnosed with stage II or III gastric cancer, and who received postoperative adjuvant chemotherapy with S-1 between June 2002 and December 2011. RESULTS: The median follow-up period was 64.3 months. The 5-year OS rate in the patients with a BWL of <15% was 59.9%, while that in the patients with a BWL of ≥15% was 36.4% (p = 0.004). Univariate and multivariate analyses for OS demonstrated that pathological T factor and BWL were significant risk factors. On the other hand, the 5-year RFS rate was 56.4% in the BWL <15% group and 36.4% in the BWL ≥15% group (p = 0.016), while univariate and multivariate analyses for RFS demonstrated that BWL was a marginally significant risk factor. CONCLUSIONS: Severe postoperative BWL, which is closely related with poor S-1 compliance, is an important risk factor for survival. It merits testing if preventing BWL improves survival of gastric cancer patients who receive S-1 adjuvant chemotherapy.

DOI： 10.1007/s10147-017-1089-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International College of Surgeons  

DOI： 10.9738/INTSURG-D-16-00171.1

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To the best of our knowledge, the clinical implications of using ribonucleoside reductase subunit M1 (RRM1) in patients who undergo curative resection and adjuvant chemotherapy have not been established. In the present study, the clinical data from 101 consecutive patients who underwent macroscopically curative resection, and who received adjuvant gemcitabine chemotherapy for pancreatic cancer at the Kanagawa Cancer Centre (Yokohama, Kanagawa, Japan) between April 2005 and December 2014 were retrospectively analyzed. The association between the RRM1 status and survival and clinicopathological features were assessed. Of the 101 patients, 41 patients expressed high levels of RRM1 expression (40.6%). Although a significant difference was observed in lymphatic invasion, there was no difference between the two groups with regard to any other clinicopathological parameters. The median follow-up period was 67.3 months. There was a significant difference between the recurrence-free survival (RFS) rates at 5 years after surgery, which were 12.9 and 0% in the high RRM1 and low RRM1 groups, respectively (P=0.042). Furthermore, there was a significant difference in the 5-year overall survival (OS) rates following surgery, which were 5.1 and 21.5% in the high RRM1 and low RRM1 groups, respectively (P=0.015). The results of the present study indicated that out of the factors assessed, RRM1 was the most important prognostic factor for OS and RFS in patients with pancreatic cancer who underwent curative resection followed by adjuvant chemotherapy with gemcitabine. Adjuvant chemotherapy with gemcitabine alone may be insufficient for the treatment of pancreatic cancer, particularly in patients with relevant risk factors.

DOI： 10.3892/ol.2017.5935

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The insulin-like growth factors (IGF) system is involved in tumor proliferation, invasion and metastasis in cancer. The current study investigated the association of IGF-1, IGF-2 and IGF-1 receptor (IGF-1R), IGF binding proteins type 3 (IGFBP-3) mRNA expression levels with clinicopathological characteristics and outcomes of 202 patients with untreated colorectal cancer (CRC). IGF-1, IGF-2, IGF-1R and IGFBP-3 mRNA expression levels were analyzed in surgical specimens of cancer tissues and adjacent normal mucosa cells using reverse transcription-quantitative polymerase chain reaction. The IGF-1R gene expression level was significantly higher in cancer tissue compared with adjacent normal mucosa. By contrast, IGF-1 gene expression levels were reduced in cancer tissue compared with normal mucosa. IGF-2 and IGFBP-3 gene expression levels did not differ significantly between cancer tissue and adjacent normal mucosa. As for the association of gene expression and clinicopathological characteristics, IGFBP-3 gene expression was significantly associated with lymph node metastasis. High IGFBP-3 gene expression was associated with poor 5-year overall survival compared with patients with low IGFBP-3 expression. Furthermore, IGFBP-3 gene expression was identified as an independent prognostic factor using multivariate analysis. Overexpression of the IGFBP-3 gene is considered an effective independent predictor of outcomes in patients with CRC.

DOI： 10.3892/ol.2017.5936

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Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients. We investigated the association of abnormal ankle brachial index (ABI), PEW, and chronic inflammation status with clinical prognosis in HD patients. A total of 973 HD patients were enrolled and were followed-up for 8 years. As a marker of the PEW, geriatric nutritional risk index (GNRI) was used. Cut-off levels were 91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein (CRP) as median value, respectively. Abnormal ABI was seen in 332 (34.1%) patients. Declined GNRI and elevated CRP levels were independently associated with abnormal ABI (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99, p = 0.0009 and OR 1.40, 95% CI 1.07-1.83, p = 0.013, respectively). GNRI levels were also independently correlated with CRP levels (β = -0.126, p < 0.0001). During follow-up period, 283 (29.1%) patients died, including 123 (12.6%) due to cardiovascular disease (CVD). Abnormal ABI (adjusted hazard ratio (HR) 1.62, 95% CI 1.13-2.32, p = 0.0096), GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06-2.33, p = 0.023) and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31-2.77, p = 0.0007) independently predicted mortality due to CVD, respectively. In conclusion, abnormal ABI, GNRI, and CRP levels were closely associated with each other, and the combination of these variables increase their predictive values for the risk of mortality due to CVD and all-cause mortality in HD patients.

DOI： 10.3390/nu9040416

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Language：Japanese   Publisher：(一社)日本外科学会  

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BACKGROUND: The short-term outcomes of laparoscopic-assisted surgery for colorectal cancer (LAC) have not been fully evaluated in elderly patients. The aim of this study was to compare the short term surgical outcomes of LAC between the patients older than 75 years and those with non-elderly patients. METHODS: This retrospective multi-institutional study selected patients who underwent LAC between April 2013 and March 2014 at Yokohama City University Hospital and its related general hospitals. The patients were categorized into two groups: elderly patients (>75 years of age: group A) and non-elderly patients (<75 years of age: group B). Surgical outcomes and post operative complications were compared between the two groups. RESULTS: A total of 237 patients were evaluated in the present study. Eighty-four patients were classified into group A, and 153 into group B. Preoperative clinicopathological outcomes demonstrated no significant differences except for the ASA score. When comparing the surgical outcomes between group A and group B, the rate of conversion to open procedure (3.6% vs 5.2%, P = 0.750), median operation time (232 min vs 232 min, P = 0.320), median blood loss (20 ml vs 12 ml, P = 0.350). The differences were not significantly different in the surgical outcomes. The incidences of > grade 2 post operative surgical complications were similar between two groups ((19.0% vs 15.7%, p = 0.587). No mortality was observed in this study. The length of postoperative hospital stay was also similar (10 days vs 10 days, p = 0.350). CONCLUSIONS: The present study suggested that LAC is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for colon cancer surgery.

DOI： 10.1186/s12893-017-0229-7

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