Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study.

PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.

Survival impact of occult liver metastasis and peritoneal dissemination compared with radiologically defined distant organ metastasis in pancreatic ductal adenocarcinoma.

BACKGROUND: Characteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported. OBJECTIVE: We aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM. METHODS: This single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images. RESULTS: OM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19-9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590). CONCLUSION: The prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.

Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: /Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications. METHODS: Twenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences. RESULTS: Of the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and ß-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01). CONCLUSIONS: The diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.

Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto.

Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.

Efficacy of Lentinula edodes Mycelia Extract on Chemotherapy-Related Tasted Disorders in Pancreatic Cancer Patients.

Patients undergoing chemotherapy suffer from taste disorders that affect the quality of life (QOL). In this study, a randomized, double-blind, placebo-controlled trial was conducted to explore the effectiveness of AHCC®, a standardized extract of cultured Lentinula edodes mycelia, for chemotherapy-related adverse events and taste disorders in patients with gastrointestinal cancer. Patients who received chemotherapy were randomized to receive either placebo or AHCC®. The study endpoints were the incidence of anemia and taste disorders assessed with changes in nutritional parameters. Ninety-eight patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study, with 55 patients randomly assigned to the AHCC® group and 43 to the placebo group. The incidence of grades 2-3 anemia in the AHCC® group who were receiving chemotherapy was not significantly different compared to that of the placebo group (Risk difference; -3.1% [95% confidence intervals (CI): -22.8% to 16.9%], p = 0.8392). In the AHCC® group, the occurrence of taste disorders during chemotherapy was significantly lower, and the nutritional parameters were significantly improved compared to those in the placebo group (Risk difference; 28.6% [95% CI: 7.5% to 47.8%], p = 0.0077). AHCC® appears to prevent taste disorders in patients with advanced PDAC who were receiving chemotherapy. AHCC® is expected to enable patients who need chemotherapy to improve nutritional status and their QOL.

The academic impact and value of an international online surgery lecture series.

Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy.

BACKGROUND: The decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas. OBJECTIVES: We aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs. METHODS: This single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis. RESULTS: After excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group. CONCLUSIONS: In patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.

High tumor budding predicts a poor prognosis in resected duodenal adenocarcinoma.

PURPOSE: Tumor budding is a histological characteristic defined as the presence of small clusters of cancer cells at the invasion front. Its significance in duodenal adenocarcinoma (DA) has not been fully described. METHODS: A single-center, retrospective study was conducted. Patients who underwent curative surgery for histologically diagnosed DA from January 2006 to December 2018 at Kansai Medical University Hospital were included. Tumor budding was counted per 0.785 mm2 and classified as low (0-4 buds), intermediate (5-9 buds), or high (≥ 10 buds). RESULTS: In total, 47 patients were included. The 5-year overall survival and relapse-free survival rates were 77% and 72%, respectively. High tumor budding was seen in 15 patients (32%). Excluding patients with superficial type (pT1) DA (n = 22), high tumor budding [hazard ratio (HR) 13.4, p = 0.028], regional lymph node metastasis (HR 19.9, p = 0.039), and adjuvant chemotherapy (HR 0.056, p = 0.036) were independent factors related to the overall survival in multivariate analyses. Distant metastases occurred significantly more often in patients who had high tumor budding than in others (p = 0.039). CONCLUSION: The data suggest that high tumor budding is a predictor of a poor prognosis in resected DA.

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

BACKGROUND: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma. METHODS: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively. RESULTS: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival. CONCLUSION: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.

Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Bile Duct Stones Predict a Requirement for Cholecystectomy in Older Patients.

BACKGROUND: The requirement for elective cholecystectomy in older patients is unclear. To determine predictors for requiring elective cholecystectomy in older patients, a prospective cohort study was performed. METHODS: All patients with gallstone disease who presented to our department from 2006 to 2018 were included if they met the following criteria: (1) age 75 years or older, (2) presentation for elective cholecystectomy, and (3) preoperative diagnosis of cholecystolithiasis. Two therapeutic options, elective surgery and a wait-and-see approach, were offered at their initial visit. Enrolled patients were assigned to one arm of the study according to their choice of the therapeutic options. The primary endpoint was the incidence of gallstone-related complications. The endpoint was compared between patients who underwent cholecystectomy (CH group) and those who chose a wait-and-see approach (No-CH group). RESULTS: During the study period, there were 344 patients in the CH group and 161 in the No-CH group. Among patients with a history of bile duct stones, the incidence of gallstone-related complications in the No-CH group was significantly higher (45% within 3 years, including two gallstone-related deaths) than that in the CH group (RR 2.66, 95% confidence interval 1.50-4.77, p = 0.0009). Among patients with no history of bile duct stones, the incidence of gallstone-related complications in the No-CH group reached only 10% over the 12 years. CONCLUSION: Cholecystectomy is recommended for older patients with both histories of cholecystolithiasis and bile duct stones, whereas a wait-and-see approach is preferable for patients with no bile duct stone history. A history of bile duct stones is a good predictor for cholecystectomy in older patients.

The past, present, and future status of multimodality treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma.

A multimodal approach to treating pancreatic ductal adenocarcinoma (PDAC) is now widely accepted. Improvements in radiological assessment have enabled us to define resectability in detail. Multimodality treatment is essential for patients, especially for those with PDAC in the borderline resectable (BR) stage. Even for disease in a resectable (R) stage, adjuvant and neoadjuvant therapies have demonstrated beneficial outcomes in several trials and analyses. Thus, there is growing interest in optimization of the perioperative therapeutic strategy. We discuss the transition of resectability criteria and the global standard of adjuvant and neoadjuvant treatments for patients with R/BR-PDAC.

Phase II Study of the Triple Combination Chemotherapy of SOXIRI (S-1/Oxaliplatin/Irinotecan) in Patients with Unresectable Pancreatic Ductal Adenocarcinoma.

LESSONS LEARNED: The triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic ductal adenocarcinoma was an effective treatment that appeared to be better tolerated than the widely used FOLFIRINOX regimen.SOXIRI regimen may provide an alternative approach for advanced pancreatic cancer. BACKGROUND: In our previous phase I study, we determined the recommended dose of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). This phase II study was conducted to assess the safety and clinical efficacy in patients with unresectable PDAC. METHODS: Patients with previously untreated metastatic and locally advanced PDAC were enrolled. The primary endpoint was response rate (RR). Secondary endpoints were adverse events (AEs), progression-free survival (PFS), and overall survival (OS). Patients received 80 mg/m2 of S-1 twice a day for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. RESULTS: Thirty-five enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8% (95% confidence interval [CI]: 10.4-40.1); median OS, 17.7 months (95% CI: 9.8-22.0); and median PFS, 7.4 months (95% CI: 4.2-8.4). Furthermore, the median OS in patients with distant metastasis was 10.1 months, whereas that in patients with locally advanced PDAC was 22.6 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). There were no treatment-related deaths. CONCLUSION: SOXIRI is considered a promising and well-tolerated regimen in patients with unresectable PDAC.

Clinicopathological and immunological features of follicular pancreatitis - a distinct disease entity characterised by Th17 activation.

AIM: Follicular pancreatitis is a recently recognised, distinct clinicopathological entity characterised by the presence of many intrapancreatic lymphoid follicles with reactive germinal centres. However, the clinicopathological and immunological features and causes have not yet been established. We assessed the clinicopathological and immunological profiles of patients with follicular pancreatitis who underwent surgery. METHODS AND RESULTS: This study included three patients with pancreatic masses (age range = 62-75 years; women:men: 1:2). A histopathological study of the resected pancreatic masses revealed abundant lymphoid follicles with reactive germinal centres in both periductal regions and diffusely within the parenchyma. No storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions were observed. The immunohistochemical examination revealed an IgG4/IgG-positive plasma cell ratio <30% in all patients. Podoplanin (Th17 marker)-expressing lymphocytes were present in the lymphoid follicles of those with follicular pancreatitis, whereas these were absent in normal lymph nodes and in lymphoid follicles of those with IgG4-related autoimmune pancreatitis (AIP). An RNA digital counting assay clearly demonstrated that the expression counts of 20 genes, including dendritic cells and lymphoid follicles markers, and related cytokines were significantly higher in follicular pancreatitis than in IgG4-related AIP (P < 0.01). The expressions of CCR6 and IL23A, which are genes related to Th17, were high. CONCLUSIONS: This study shows that follicular pancreatitis is a histopathologically and immunologically distinct disease entity of pancreatitis and is characterised by upregulated Th17 expression.

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis.

OBJECTIVE: Adipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC. METHODS: By immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed. RESULTS: Of the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses. CONCLUSIONS: Adipophilin is a potential independent prognostic marker for PDAC.

The impact of low body mass index on postoperative outcomes in pancreatectomy patients: a retrospective analysis of Japanese administrative data.

PURPOSE: To comparatively examine in-hospital mortality among different underweight body mass index (BMI) categories in pancreatic cancer patients after pancreatectomy in Japan. METHODS: We conducted a large-scale multi-center retrospective cohort study of adult patients with pancreatic cancer who underwent pancreatectomy between April 1, 2010 and March 31, 2016. Patients were classified according to BMI as follows: normal BMI (18.50-24.99 kg/m2), mild thinness (17.00-18.49 kg/m2), moderate thinness (16.00-16.99 kg/m2), and severe thinness (< 16.00 kg/m2). A multivariable logistic regression analysis was performed with in-hospital mortality as the dependent variable and BMI groups as the main independent variable of interest. RESULTS: We analyzed 6173 patients from 332 hospitals. The results showed that the severe thinness group had a longer postoperative hospital stay (34.4 ± 25.6 days) and higher incidence of postoperative pneumonia (5.5%) than the other groups. The generalized estimating equations accounted for patient demographics, surgical procedure, anesthetic technique, activities of daily living score, and Charlson comorbidity index as covariates. Relative to the normal BMI group, the odds ratios for in-hospital mortality were 0.57 (95% confidence interval: 0.26-1.24; P = 0.16) in the mild thinness group, 1.49 (0.64-3.48; P = 0.36) in the moderate thinness group, and 2.54 (1.05-6.08; P = 0.04) in the severe thinness group. CONCLUSION: Severe thinness was significantly associated with a higher risk of mortality, and extremely low BMI should be considered a risk factor in pancreatectomy patients.

Comparison of surgical outcomes of three different stump closure techniques during distal pancreatectomy.

BACKGROUND: To find the appropriate method of pancreatic transection during distal pancreatectomy (DP), we retrospectively compared post-operative complications including postoperative pancreatic fistula (POPF) according to the different types of pancreatic transection. METHODS: This study included 169 patients who underwent pancreatic transection using an ultrasonic activated device (USAD) with transfixion of the pancreatic duct (DP-TF group, n = 89), USAD followed by pancreaticogastrostomy (DP-PG group, n = 44), and a reinforced linear tristapler (DP-ST, n = 36). RESULTS: Overall and POPF-related complications in DP-PG group, and delayed gastric emptying (DGE) in DP-ST group were significantly lower than DP-TF group. There were no significant difference in overall complication, length of hospitalization and operative costs between DP-PG and DP-ST groups. Operative time was significantly longer in DP-PG group than others. CONCLUSION: Both DP-PG and DP-ST are associated with better surgical outcomes. Regarding ease of surgical technique, shorter operative times, and similar medical costs, DP with a reinforced linear tristapler is a good choice during DP.

PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. METHODS: This study included 42 patients with PDAC who underwent pancreatectomy. We evaluated PD-L1 expression in these patients using PID staining and correlated PD-L1 expression level with each patient's clinico-pathological features. RESULTS: PD-L1 expression was detected in 61.9% (26/42) of the patients with PDAC by PID staining. There was a significant difference in overall survival between PD-L1-positive and PD-L1-negative patients [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.00-4.54; P = 0.049]. Among CD8+-tumor-infiltrating lymphocyte-positive cases, the overall survival of PD-L1-positive patients was significantly poorer than that of PD-L1-negative patients (HR 3.84, 95% CI 1.59-10.35; P = 0.003). Univariate and multivariate analyses indicated that PD-L1 expression was an independent predictive poor prognostic factor in patients with PDAC. CONCLUSIONS: PD-L1 expression appears to be an important prognostic factor in patients with PDAC who underwent surgical resection.

Clinical outcomes of pancreatic ductal adenocarcinoma resection following neoadjuvant chemoradiation therapy vs. chemotherapy.

PURPOSE: We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC). METHODS: The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups. RESULTS: The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage ≥IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse. CONCLUSION: NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148).