記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Programmed cell death-1 (PD-1) and its ligand PD-L1 play crucial roles in cancer-related immunosuppression. Previous reports have hinted at the potential of neoadjuvant chemoradiotherapy (NACRT) to shift the immunosuppressive microenvironment of pancreatic adenocarcinoma (PDAC) toward an immunogenic state in selected patients. This study aimed to assess the effects of NACRT on PD-L1 expression and PD-1+ lymphocyte infiltration in PDAC. PATIENTS AND METHODS: Eighty-two patients with PDAC underwent surgical resection. Among them, 55 patients with borderline-resectable PDAC (BR-PDAC) received NACRT, while 27 patients with resectable PDAC underwent straightforward resection without NACRT. Using immunohistochemical staining, resected specimens were examined to assess PD-1+ tumor-infiltrating lymphocytes (TILs), CD8+ TIL, forkhead box P3 positive (Foxp3+) TILs, and PD-L1 expression in tumor cells. RESULTS: High PD-L1 expression correlated positively with NACRT treatment and inversely with PD-1+ TILs. A high CD8+ TILs level was strongly correlated to PD-L1 expression. The numbers of PD-1+ TILs and Foxp3+ TILs were significantly correlated in the straight-line group but not in the NACRT group. In both groups, no significant correlation was found between the overall survival of patients and PD-1+ TILs or PD-L1 expression alone. CONCLUSION: NACRT in pancreatic cancer may affect TILs and PD-L1 expression, thereby improving the immunosuppressive microenvironment and implying a potential synergy between checkpoint inhibitors and radiation treatment.

DOI： 10.21873/anticanres.17554

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

DOI： 10.1002/jhbp.1437

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Although surgery is the mainstay of curative-intent treatment for extrahepatic biliary tract cancer (EBTC), recurrence following surgery can be high and prognosis poor. The impact of neoadjuvant therapy (NAT) relative to upfront surgery (US) among patients with EBTC remains unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) databases was utilized to identify patients who underwent surgery from 2006 to 2017 for EBTC, including gallbladder cancer (GBC) and extrahepatic cholangiocarcinoma (ECC). Trends in NAT utilization were investigated, and the impact of NAT on prognosis was compared with US using a propensity score-matched (PSM) analysis. Results: Among 6582 EBTC patients (GBC, n = 4467, ECC, n = 2215), 1.6% received NAT; the utilization of NAT for EBTC increased over time (Ptrend = 0.03). Among patients with lymph node metastasis, the lymph node ratio was lower among patients with NAT (0.18 vs. 0.40, p < 0.01). After PSM, there was no difference in overall survival (OS) and cancer-specific survival (CSS) among patients treated with NAT versus US (5-year OS: 24.0% vs. 24.6%, p = 0.14, 5-year CSS: 38.0% vs. 36.1%, p = 0.21). A subgroup analysis revealed that NAT was associated with improved OS and CSS among patients with stages III-IVA of the disease (OS: HR 0.65, 95%CI 0.46-0.92, p = 0.02, CSS: HR 0.62, 95%CI 0.41-0.92, p = 0.01). Conclusions: While NAT did not provide an overall benefit to patients undergoing surgery for EBTC, individuals with advanced-stage disease had improved OS and CSS with NAT. An individualized approach to NAT use among patients with EBTC may provide a survival benefit.

DOI： 10.3390/jcm12072654

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00620&link_issn=&doc_id=20230316010010&doc_link_id=10.18888%2Fop.0000003199&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fop.0000003199&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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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 previously observed higher prevalence of high-grade pancreatic intraepithelial neoplasia (PanIN) in LSL-KrasG12D/+; Pdx1Cre/+ (KC-Crmp4wild) mice than LSL-KrasG12D/+; Pdx1Cre/+; Crmp4-/- (KC-Crmp4-/-) mice. This study investigated the relationship between collapsin response mediator protein 4 (CRMP4) and immune cell infiltration in pancreatic cancer. MATERIALS AND METHODS: PanIN was induced by intraperitoneal injection of caerulein into KC-Crmp4wild and KC-Crmp4-/- mice, and immune cells in PanIN lesions were compared. Subcutaneous tumors were created by injecting Pan02 cells, and tumor diameter was compared between Crmp4wild and Crmp4-/- mice every 7 days. Peritumoral immune cells were examined immunohisto chemically. RESULTS: High-grade PanIN in KC mice showed statistically significantly high expression of CD163 (p=0.031) and CD11b (p=0.027). Following subcutaneous injection of Pan02 cells, tumor diameter was greater in Crmp4wild mice than Crmp4-/- mice. Crmp4wild mice exhibited higher CD163 and CD11b expression than Crmp4-/- mice in tumors (p<0.001). CONCLUSION: CRMP4 might promote pancreatic cancer by up-regulating M2 macrophages and myeloid-derived suppressor cells.

DOI： 10.21873/anticanres.15537

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3 V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 months vs. 30.9 months. p = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery (p = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSIONS: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

DOI： 10.1097/SLA.0000000000005330

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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：(一社)日本消化器外科学会  

DOI： 10.5833/jjgs.2020.0104

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. PATIENTS AND METHODS: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. RESULTS: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)]. CONCLUSIONS: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.

DOI： 10.1245/s10434-021-09811-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Extrahepatic cholangiocarcinoma requires invasive surgery and is associated with poor prognosis; thus, a prognostic biomarker is highly needed. Extrahepatic cholangiocarcinoma is sub-classified into two types based on their location, namely perihilar and distal. Perihilar cholangiocarcinoma requires lobectomy as curative surgical resection, whereas the distal requires pancreatoduodenectomy. HMGA2 overexpression is reported to correlate with progression, aggressiveness, dissemination and poor prognosis in several types of cancers. Although its association with extrahepatic cholangiocarcinoma has been reported, none of the previous studies assessed its significance in each subtype. METHODS: We assessed the expression of HMGA2 protein in surgical specimens after curative intent surgery in 80 patients including 41 with perihilar cholangiocarcinoma and 39 with distal cholangiocarcinoma by immunohistochemistry. We then examined its association with clinicopathological findings and patient survival outcomes. RESULTS: We found that HMGA2 was expressed in 51% (21 of 41) of perihilar cholangiocarcinoma and 41% (16 of 39) of distal cholangiocarcinoma samples. In perihilar cholangiocarcinoma, we found significant correlations between expression and vascular invasion and perineural invasion. In distal cholangiocarcinoma, we found that protein levels correlated with tumor grade. Univariate and multivariate analyses demonstrated that HMGA2 expression was an independent poor prognostic factor for patients with both subtypes of disease. CONCLUSIONS: Our results revealed that HMGA2 expression as an independent prognostic marker for both perihilar and distal cholangiocarcinoma that were resected with curative intent.

DOI： 10.1016/j.ejso.2020.08.005

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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.2020.0061

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Asia  

DOI： 10.1002/jhbp.746

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Unresectable pancreatic cancer (UR-PC) has a poor prognosis. Although conversion surgery has been considered a promising strategy for improving prognosis in UR-PC, the clinical benefit offered to patients with UR-PC remains controversial. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PC. METHODS: We evaluated patients with UR-PC referred to our department for possible surgical resection between January 2008 and June 2017. Resectability was evaluated using multimodal imaging in patients who underwent chemotherapy for more than 6 months. Conversion surgery was performed only in patients who were judged eligible for R0 resection. RESULTS: In total, 90 patients were evaluated. Among them, only 22 (24.4%) could actually undergo conversion surgery, and the R0 resection rate was 72.7% (16/22). Although Evans grade ≥ IIB was noted in six patients (27.3%), none achieved complete response (CR). The median survival time was significantly longer among patients who underwent conversion surgery than in the unresected patients who underwent chemotherapy (21.3 months vs. 12.6 months; p < 0.001). Multivariate and Kaplan-Meier analyses revealed microvascular invasion to have a significant adverse effect on recurrence-free survival (RFS: 7 months vs. not reached, p = 0.004) and overall survival (OS: 21 months vs. 85 months, p = 0.047). CONCLUSIONS: After long-term chemotherapy, conversion surgery for UR-PC is associated with long-term survival. Microvascular invasion is predictive of poor prognosis in these patients; adjuvant protocols are therefore needed for patients with microvascular invasion.

DOI： 10.1007/s00268-020-05503-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic intraepithelial neoplasia (PanIN), the most common premalignant lesion of the pancreas, is a histologically well-defined precursor to invasive pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms underlying the progression of PanINs have not been fully elucidated. Previously, we demonstrated that the expression of collapsin response mediator protein 4 (CRMP4) in PDAC was associated with poor prognosis. The expression of CRMP4 was also augmented in a pancreatitis mouse model. However, the role of CRMP4 in the progression of PanIN lesions remains uncertain. In the present study, we examined the relationship between CRMP4 expression and progression of PanIN lesions using genetically engineered mouse models. PanIN lesions were induced by peritoneal injection of the cholecystokinin analog caerulein in LSL-KRASG12D; Pdx1-Cre (KC-Crmp4 wild-type, WT) mice and LSL-KRASG12D; Pdx1-Cre; Crmp4-/- (KC-Crmp4 knockout, KO) mice. We analyzed pancreatic tissue sections from these mice and evaluated PanIN grade by hematoxylin and eosin staining. CRMP4 expression was examined and the cellular components assessed by immunohistochemistry using antibodies against CRMP4, CD3, and α-smooth muscle actin (SMA). The incidence of high-grade PanIN in KC-Crmp4 WT mice was higher than that in KC-Crmp4 KO animals. CRMP4 was expressed not only in epithelial cells but also in αSMA-positive cells in stromal areas of PanIN lesions. The CRMP4 expression in stromal areas correlated with PanIN grade in WT mice. These results suggested that the expression of CRMP4 in stromal cells may underlie the incidence or progression of PanIN.

DOI： 10.1016/j.tranon.2020.100746

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Increasing evidence suggests that cancer-associated inflammation, as indicated by markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), predicts poor outcomes in pancreatic cancer. In this study, the associations between systemic inflammation markers and survival were examined in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) patients who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection. METHODS: From April 2009 to December 2017, 119 patients diagnosed with BR-PDAC and receiving NACRT followed by radical surgery were included in this retrospective study. The associations between the pre- and post-NACRT NLR, PLR, mGPS, and clinicopathological characteristics, as well as their predictive values for survival outcomes, were analyzed. This study was approved by an institutional review board at Yokohama City University (B180600049). RESULTS: On multivariate analysis with a Cox's proportional hazards regression model, post-NACRT NLR ≥3 (p = 0.040; hazard ratio, 2.24; 95% CI 1.28-3.91) and lymph node metastasis (p = 0.002; hazard ratio, 2.33; 95% CI 1.36-3.99) were significantly associated with shorter overall survival. The median survival time was 22.0 months for patients with post-NACRT NLR ≥3 and 45.0 months for patients with post-NACRT NLR <3 (p = 0.028). CONCLUSIONS: The NLR following NACRT might predict survival in BR-PDAC patients. Patients with an elevated post-NACRT NLR or positive lymph node metastasis may be candidates for stronger adjuvant therapies.

DOI： 10.1007/s00268-019-05159-9

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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 identify risk factors of early recurrence after neoadjuvant chemoradiation therapy (NACRT) and curative pancreatectomy in patients with borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Sixty-one patients with BR-PDAC who underwent curative resection after NACRT during July 2009-June 2014 were included. Patients were divided into early recurrence (i.e., developed recurrence within 1 year after pancreatectomy; n=30) and late/non-recurrence groups (n=31). The patient characteristics, clinicopathological factors of early recurrence, and survival time were retrospectively compared between groups. RESULTS: In the univariate analysis, the maximum standardized uptake value (SUVmax), microvascular invasion, and lymph node metastasis were associated with early recurrence. In the multivariate analysis, the pre-NACRT SUVmax and microvascular invasion in the early recurrence group were significantly different from that in the late/non-recurrence group. A pre-NACRT SUVmax >4.1 was an independent predictor of poor recurrence-free and overall survival. CONCLUSION: SUVmax and microvascular invasion are independent predictors of poor recurrence-free and overall survival after NACRT for BR-PDAC. Although complete pancreatectomy after NACRT was performed, approximately half of the patients had recurrence within 1 year.

DOI： 10.21873/anticanres.13615

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DOI： 10.1097/MD.0000000000016673

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer New York LLC  

DOI： 10.1007/s00268-018-04883-y

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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 Journal of Cancer and Chemotherapy Publishers Inc.  

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DOI： 10.1186/s40792-018-0487-3

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DOI： 10.1007/s00280-018-3566-z

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PubMed

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記述言語：英語  

BACKGROUND: Predicting chemosensitivity to neoadjuvant chemoradiotherapy (NACRT) in pancreatic cancer is desired. The present study aimed to examine the relationship between intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) and the outcomes of NACRT with gemcitabine (GEM) combined with S-1 in patients with borderline-resectable pancreatic cancer (BRPC). MATERIALS AND METHODS: Forty-seven patients who underwent NACRT with GEM plus S-1, following curative surgery, were recruited in our Institution between 2009 and 2012. Immunohistochemical expressions of hENT1, TS, and DPD in fine-needle aspiration (FNA) biopsies and resected specimens were examined. The correlation between these enzyme expressions and long-term outcome was analyzed. RESULTS: In 21 FNA specimens, no relationship between clinical responses to NACRT and long-term survival was found. However, in 47 resected specimens, patients were classified according to the number of favorable hENT1, TS, and DPD expression factors (hENT1 positive/TS negative/DPD negative). The presence of three favorable factors was strongly associated with improved partial response rates to NACRT (p=0.002). Patients with 2 or more favorable factors showed a significantly longer overall survival than the other patients (p=0.002). CONCLUSION: Combined expression analyses of hENT1, TS, and DPD may predict long-term outcomes in patients with BRPC after NACRT.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.surg.2013.12.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ejso.2013.10.007

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5833/jjgs.45.340

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1440-1746.2008.05662.x

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝胆膵外科学会  

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記述言語：日本語   出版者・発行元：一般社団法人日本外科学会  

CiNii Books

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記述言語：日本語   出版者・発行元：一般社団法人日本外科学会  

CiNii Books

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記述言語：日本語   出版者・発行元：日本臨床社  

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記述言語：日本語   出版者・発行元：南江堂  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

DOI： 10.3919/jjsa.74.367

J-GLOBAL

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記述言語：日本語   出版者・発行元：金原出版  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本外科感染症学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：一般社団法人日本外科学会  

CiNii Books

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記述言語：日本語   出版者・発行元：一般社団法人日本外科学会  

CiNii Books

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

DOI： 10.3919/jjsa.73.693

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：一般社団法人日本外科学会  

CiNii Books

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記述言語：日本語  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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