記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Irinotecan and trifluridine/tipiracil (FTD/TPI) are fourth-line treatment options after third-line nivolumab for advanced gastric cancer (AGC). However, the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab remains unclear. This study aimed to evaluate the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab. PATIENTS AND METHODS: We identified 137 AGC patients treated with nivolumab as third-line treatment in our institute between October 2017 and July 2021. Of these, we recruited 19 AGC patients who initiated irinotecan and 23 AGC patients who initiated FTD/TPI in the fourth-line setting until September 2021. RESULTS: The median overall survival was 5.83 months for irinotecan and 6.31 months for FTD/TPI. Median time-to-treatment failure was 2.07 months for irinotecan and 1.64 months for FTD/TPI. While the frequency of all-grade diarrhea was higher in irinotecan (36% vs. 17%), grade ≥3 neutropenia tended to be higher in FTD/TPI (21% vs. 35%). CONCLUSION: Irinotecan and FTD/TPI may be clinically useful as fourth-line treatments after nivolumab.

DOI： 10.21873/anticanres.16452

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs). These anti-dsGAG/NA antibodies matured and expanded via intratumoral immunological driving force of innate immunity via NAs. These human cancer-derived antibodies exhibited acidic pH-selective affinity across both antigens and showed specific reactivity to diverse spectrums of human tumor cells. The antibody-drug conjugate exerted therapeutic effects against multiple cancers in vivo by targeting cell surface dsGAG antigens. This study reveals that intratumoral immunological reactions propagate tumor-oriented immunoglobulin clones and demonstrates a new therapeutic modality for the universal treatment of human malignancies.

DOI： 10.1111/cas.15596

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial-mesenchymal transition (EMT) and cell-cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell-cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18-ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

DOI： 10.3390/cancers14020290

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.

DOI： 10.1038/s42003-020-01305-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Tumor microenvironments consist of many types of immune cells, in which regulatory T-cells (Tregs) are supposed to play important roles to suppress anti-tumor immunity. Regional lymph nodes are essential for antitumor immunity in colorectal cancer (CRC). In this study, we compared the diversity of phenotypes of T-cells in normal tissue and regional lymph nodes in order to determine the immunosuppressive mechanism of lymph node metastasis of CRC. PATIENTS AND METHODS: Fifty patients were enrolled in this study, and paired samples (tumor tissue, normal tissue, and three regional lymph node samples and as well as non-regional lymph node samples) were obtained from each patient. In each paired-sample set, the proportions of different immune cell types and T-cells expressing immune checkpoint molecules were compared using flow cytometry. RESULTS: Higher proportions of Tregs [7.58% (4.94%-13.87%) vs. 1.79% (0.03%-5.36%), p<0.001] and lower proportions of INFγ-producing CD4-positive T (iCD4+) cells [21.49% (12.08%-27.35%) vs. 26.55% (15.65%-37.63%), p<0.001] were observed in tumor tissue than in normal mucosa. Parts of regional lymph nodes nearest the tumor had a greater proportion of Tregs [5.86% (4.18%-7.69%)] and lower proportions of iCD4+ [5.94% (3.51%-9.04%)] and INFγ-producing CD8-positive T (iCD8+) cells [21.93% (14.92%-35.90%)] than distant parts of regional lymph nodes and non-regional lymph nodes. Both immune-suppressing molecules (CTLA-4 and PD-1) and immune-promoting molecules (OX-40 and ICOS) tended to be highly expressed in tumor tissue and local lymph nodes. CONCLUSION: In patients with CRC, regional lymph nodes, especially the parts nearest the tumor, had a higher proportion of Tregs and other suppressive immunophenotypes of T-cells than those located more distantly.

DOI： 10.21873/invivo.11848

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 72-year-old man presented with right lower abdominal pain. Abdominal enhanced CT showed a large tumor in the ascending colon. Colonoscopyrevealed a type 2 tumor infiltrating three-quarters of the ascending colon. The biopsyspecimen showed a malignant lymphoma. Thus, the patient underwent ileocecal resection with D3 lymph node dissection. The histopathological diagnosis was primarydiffuse large B-cell lymphoma of the ascending colon. Post-operative PET-CT showed disseminated extra-nodal involvement, Stage Ⅳ(Lugano staging system). He was administered 2 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy. However, the patient was diagnosed with progressive disease. He received several chemotherapies and finallydied 8 months after surgery. We report our present case and literature review.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 74-year-old man was admitted to our hospital with multiple liver tumors detected by routine ultrasonography. Colonoscopy showed a type 2 tumor measuring approximately 25mm in diameter at the terminal ileum. The biopsy specimen showed neuroendocrine tumor(NET)G1. The patient was diagnosed with NET G1 of the ileum with multiple liver metastases. Thus, he underwent ileocecal resection with lymph node dissection and liver(S2)biopsy. A tumor was observed at the terminal ileum with serosal invasion, and the mesenteric lymph nodes were enlarged. Multiple liver metastatic tumors were observed in S2, S5, and S8. The patient was diagnosed with NET G1 of the ileum, T4N1M1, Stage Ⅳ. He is receiving octreotide therapy and has maintained stable disease for about 24 months.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

An 84-year-old man visited our hospital with epigastralgia.Levels of hepatic and biliary enzymes and CRP were elevated, as detected by a blood test.On a CT scan, a swollen gallbladder with stones was detected.The patient was admitted to the hospital with a diagnosis of Grade I acute cholecystitis.Conservative treatment was continued with antibiotic administration and the patient was discharged from the hospital with improvement on day 6 after admission.Three months later, the patient underwent laparoscopic cholecystectomy.In the gallbladder, a 45×45 mm tumor was found.Upon pathological examination, diffuse proliferation of lymphocyte-like heterotypic cells and subserosal invasion were observed.Immunohistochemistry results were negative for MUM1 and positive for CD10 and Bcl6 markers.A malignant diffuse large B-cell lymphoma was diagnosed.We experienced a case of malignant lymphoma of the gallbladder diagnosed after surgery for acute cholecystitis, which we herein report with literature consideration.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pap>por2>sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Gastroenterological Surgery  

DOI： 10.5833/jjgs.2016.0173

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of this study was to evaluate the safety and feasibility of gastrectomy in elderly patients aged over 80 years. PATIENTS AND METHODS: A total of 393 patients who underwent gastrectomy for gastric cancer were assigned to 2 groups: those aged over 80 years(n=48; elderly group)and those less than 80 years(n=345).Clinicopathological features, operative factors, post-operative complications(Clavien-Dindo Grade II or higher), and mortality were retrospectively analyzed. RESULTS: Rates of distal gastrectomy(73% vs 59%, p=0.043)and D1 or D1+dissection(73% vs 58%, p=0.046)were significantly higher in the elderly group.There were no significant differences in post-operative complication rates(23% vs 20.3%, p=0.255)or mortality rates(2.1% vs 0.6%). CONCLUSION: Our results indicate that gastrectomy in elderly patients aged over 80 years may be safe and feasible.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The patient was an 82-year-old man, who contracted chronic hepatitis C in 1977. In 1997, he was diagnosed with intraductal papillary-mucinous neoplasm (IPMN), and was treated with surgery. In August 2005, cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC) were detected, and he underwent a subsegmentectomy of the liver. In February 2007, he had a supradiaphragmatic lymph node recurrence of CCC. It was a solitary lesion; therefore, we resected the recurrent tumor by thoracoscopic surgery. In January 2012, squamous cell lung cancer was detected and he had a thoracoscopic operation. Furthermore, in February 2015, 2HCCs were detected in S5 and S5/8 of the liver. He underwent radiofrequency ablation. Over the course of 18 years, this patient developed cancers in his pancreas, intrahepatic bile duct, liver, and lung. However, the patient has survived without recurrence because of aggressive therapy and diligent surveillance after surgery.

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