Reevaluation of regional lymph nodes in patients with pancreatic ductal adenocarcinoma in the pancreatic body and tail.

Introduction: In patients with pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body (Pb) and tail (Pt), the appropriate area for lymphadenectomy is controversial. This study aimed to reevaluate the extent of lymph node (LN) metastasis in Pb- and Pt-PDAC, and to define the optimal area of LN dissection. Patients and methods: This single-center retrospective study evaluated patients with Pb- and Pt-PDAC who underwent distal pancreatectomy with extended lymphadenectomy between 2006 and 2020. LN metastasis in >3.0% of patients were defined as new regional LN. Results: The study cohort included 135 patients with Pb-PDAC and 42 patients with Pt-PDAC. In patients with Pb-PDAC, LNs around the splenic artery (SPA) had the highest metastasis-positive rate (54.1%). LNs along the left gastric artery, common hepatic artery, celiac axis (CA), superior mesenteric artery (SMA), and splenic hilus were defined as new regional LNs. In patients with Pt-PDAC, LNs at the splenic hilum had the highest metastasis-positive rate (38.1%). The station and LN around the SPA were defined as new regional LNs in those with Pt-PDAC. Metastasis beyond the newly defined regional LNs was not associated with survival. The incidence of LN metastasis was lower in patients who received preoperative chemotherapy than in those who underwent upfront surgery in both Pb- and Pt-PDAC. Conclusion: Although it needs to be verified in future multicenter studies, LN of both the CA and SMA systems should be dissected in patients with Pb-PDAC. However, only those around the SPA and splenic hilus should be dissected routinely in those with Pt-PDAC.

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.

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.

Intraperitoneal Paclitaxel Treatment for Patients with Pancreatic Ductal Adenocarcinoma with Peritoneal Dissemination Provides a Survival Benefit.

Background: Intraperitoneal chemotherapy using paclitaxel (i.p.-PTX) is expected to be a new therapeutic strategy for patients with pancreatic ductal adenocarcinoma (PDAC) and peritoneal dissemination. We evaluated the survival benefit of i.p.-PTX compared with standard systemic chemotherapy. Methods: Clinical data of 101 consecutive PDAC patients with peritoneal dissemination between 2007 and 2018 were analyzed. All patients were determined to have no other sites of distant organ metastasis to the lung, bone, or liver on contrast-enhanced CT imaging. Patients underwent staging laparoscopy or open laparotomy to confirm pathological evidence of peritoneal dissemination, and to exclude occult liver metastasis. Survival curves were estimated using the Kaplan−Meier method, and differences were compared using the log-rank test. Results: Forty-three patients were treated with i.p.-PTX (i.p.-PTX group) and forty-nine patients received standard systemic chemotherapy (Ctrl group). Nine patients did not receive any treatment (BSC group). The median survival time (MST) in the i.p.-PTX group was significantly longer than that in the Ctrl group (17.9 months vs. 10.2 months, p = 0.006). Negative peritoneal washing cytology was observed in 24 out of 43 patients in the i.p.-PTX group. The i.p.-PTX group tended to have a higher proportion of clinical responses than the Ctrl group (30% vs. 18%, p = 0.183). Conversion surgery was performed in 10 patients in the i.p.-PTX group and 2 patients in the Ctrl group after confirming disappearance of peritoneal dissemination with staging laparoscopy or open laparotomy (p = 0.005). The MST in patients who underwent surgical resection was significantly longer than that in patients who did not (27.4 months vs. 11.3 months; p < 0.0001). Conclusion: i.p.-PTX therapy provided improved survival in PDAC patients with peritoneal dissemination, and conversion surgery enhanced it in patients with favorable responses to chemotherapy. i.p.-PTX might become one of the treatment options to PDAC patients with peritoneal dissemination.

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.

Risk factors and treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy: A retrospective study.

BACKGROUNDS/PURPOSE: The purpose of this study was to identify risk factors and establish a treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy. METHODS: The 443 patients who underwent PD from April 2006 to December 2015 were analyzed. Clinical characteristics were compared between patients with and without clinical HJ stenosis, and risk factors for clinical HJ stenosis were analyzed. In addition, the treatment and clinical course of patients with clinical HJ stenosis were retrospectively reviewed. RESULTS: Clinical HJ stenosis defined with intrahepatic bile duct dilatation was identified in 40 patients (9.0%). Multivariate analysis revealed that the independent risk factor for clinical HJ stenosis was the hepatic duct at surgery ≤8 mm. Endoscopic HJ stenosis was identified in 36 patients, and 31 patients were treated successfully with double balloon endoscopic retrograde cholangiography; five patients required re-anastomosis (n = 3) and percutaneous transhepatic biliary drainage (n = 2). Complete obstruction of HJ was found in five patients, and treatment with DB-ERC was successful in only one patient. CONCLUSION: The independent risk factor for clinical HJ stenosis was hepatic duct diameter ≤8 mm. Most cases of endoscopic HJ stenosis were treated successfully with DB-ERC, except in patients with complete obstruction.

Validation of the triple-checked criteria for drain management after pancreatectomy.

BACKGROUND: Drain management is important for the detection and treatment of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously established the triple-checked criteria for drain removal: drain fluid amylase (DFA) <5000 U/L on postoperative day (POD) 1 and DFA <3000 U/L on POD 3, or C-reactive protein <15 mg/dL on POD 3. This study aimed to validate the efficacy of the triple-checked criteria. METHODS: In this study, 681 patients who underwent pancreatectomy were included. Drains were removed according to our previous criteria (sequentially checked criteria: DFA <5000 U/L on POD 1 and DFA <3000 U/L on POD 3) from 2012 to 2016 (control group) and the triple-checked criteria from 2017 to 2019 (intervention group). RESULTS: The control group included 406 patients, and the intervention group included 275 patients. Significantly more patients (n = 237, 86.2%) met the triple-checked criteria in the intervention group, relative to the sequentially checked criteria for early drain removal policy (n = 309, 76.1%; P = .001). Sensitivity, accuracy, and negative predictive value were significantly higher in the intervention group than in the control group (P < .001). The incidence of CR-POPF was not significantly different (11.1% vs 13.8%, P = .285). CONCLUSIONS: The triple-checked criteria contributed to effective drain removal after pancreatectomy without increasing CR-POPF.

Estimation of the degree of surgical difficulty anticipated for pancreatoduodenectomy: Preoperative and intraoperative factors.

BACKGROUND: Pancreatoduodenectomy (PD) is a technically complex procedure. Preoperative anticipation of the degree of difficulty could contribute to patient safety during trainee surgical education. METHODS: We prospectively administered a questionnaire to the chief surgeon after each PD performed between 2016 and 2018 at our institution (99 consecutive patients). The surgeon rated the difficulty of the procedure; we then analyzed this information against perioperative data. RESULTS: The difficulty of PD was ranked as simple (29.3%), moderate (40.4%), or difficult (30.3%). The difficult procedures required an operative time of 2 h longer than the simple procedures and involved an additional 800 mL of intraoperative blood loss. Postoperative complications were similar in all groups. Multivariate analysis revealed that an unrecognized tissue plane for dissection was an independent determinant of a difficult PD (odds ratio [OR]: 89.2, 95% confidence interval [CI]: 9.2-861.2; P < .001). Independent predictors of a difficult PD were a pretreatment status of borderline resectable or unresectable (OR: 21.9, CI: 5.3-90.6; P < .001) and cholangitis during the preoperative period (OR: 4.1, CI: 1.3-13.0; P = .017). CONCLUSIONS: Surgeons deem the PD procedure to be difficult when the proper tissue plane for dissection is unrecognized. Preoperative assessment of the anticipated difficulty could contribute to better operative management.

A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC. METHODS: Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020. RESULTS: Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P < .0001) and "high-risk markers" (OR 2.07, P = .011) as independent predictors of OAM. A scoring system consisting of body/tail (yes: 1, no: 0) and "high-risk markers" (yes: 1, no: 0) was constructed. In the validation cohort, when staging laparoscopy (SL) was performed for patients with scores 1/2, the eligibility for SL, sensitivity, and negative predictive value of OAM were 55%, 91%, and 96%, respectively. CONCLUSIONS: Tumor location of body/tail and "high-risk markers" were independent predictors of OAM, composing our simple and reproducible risk scoring system.

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.

Clinicopathological characteristics of pancreatic ductal adenocarcinoma with invasive micropapillary carcinoma component with emphasis on the usefulness of PKCζ immunostaining for detection of reverse polarity.

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component. Clinicopathological characteristics were compared between the IMPC and non-IMPC groups. Immunohistochemical staining for PKCζ was performed using an autostainer. In total, 14 cases had an IMPC component (5.8%). The extent of IMPC component ranged from 5 to 20%. There were no significant differences in tumor location, T category, lymph node metastatic status, preoperative carbohydrate antigen 19-9 level, resection status and overall survival between the IMPC and non-IMPC groups. Immunostaining for PKCζ clearly showed reverse polarity of the neoplastic cells of IMPC. Although previous reports have shown that the presence of an IMPC component (>20% of the tumor) indicated poor prognosis, the present study demonstrated that presence of IMPC <20% did not suggest a worse prognosis.

Benefits of Conversion Surgery after Multimodal Treatment for Unresectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC. METHODS: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months). RESULTS: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, p < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, p = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS. CONCLUSION: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.

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.

Prognosis in Patients With Gallbladder Edema Misdiagnosed as Cholecystitis.

BACKGROUND AND OBJECTIVES: Edema of the gallbladder may pose a diagnostic challenge because it also occurs in patients without an indication for cholecystectomy. METHODS: We evaluated all consecutive patients with gallstone disease who presented for cholecystectomy at the Department of Surgery of Kansai Medical University from January 2006 to April 2019. Using the prospectively collected database in our department, we obtained information on patients whose final diagnoses were gallbladder edema. We identified 12 patients with gallbladder edema who were misdiagnosed with acute cholecystitis among 2661 patients and who presented for cholecystectomy for benign gallbladder diseases. The outcome of these patients was assessed to prevent unnecessary cholecystectomy. RESULTS: In all 12 patients, computed tomography and ultrasonographic imaging showed gallbladder wall thickening. Acute cholecystitis was suspected, and emergent cholecystectomy was performed for the first 5 patients. Of these 5 patients, 2 patients died of liver failure postoperatively. Based on the misdiagnosis in the first 5 patients, the latter 7 patients did not undergo cholecystectomy; instead, they were treated specifically for their systemic disease. To date, no cholecystitis has occurred in these 7 patients. In all misdiagnosed cases in the present report, mesh-like wall thickening was a distinctive feature of gallbladder edema on ultrasonography. We consider this feature important for distinguishing simple gallbladder edema from cholecystitis. CONCLUSION: Careful evaluation of clinical symptoms and imaging findings, especially mesh-like wall thickening on ultrasonography, is necessary in this setting to prevent misdiagnosis and unnecessary cholecystectomy.

Clinical impact of the sequentially-checked drain removal criteria on postoperative outcomes after pancreatectomy: a retrospective study.

BACKGROUND: Strict criteria for impeccably safe drain management following pancreatectomy have not yet been developed. We evaluated the utility of the sequentially-checked drain removal criteria by comparison with conventional criteria. METHODS: Postoperative outcomes of 801 patients who underwent pancreatectomy, including 395 patients for whom drain fluid amylase (DFA) < 375U/l on postoperative day (POD) 3 (control group), were used and 406 patients for whom the sequentially-checked criteria of DFA <5,000 U/l on POD 1 and DFA <3,000 U/l on POD 3 (sequentially-checked group) were used and were retrospectively evaluated. RESULTS: DFA on POD 3 and fistula risk score did not differ between groups. Significantly more patients in the sequentially-checked group met the criteria (control, 63.8% vs. sequentially-checked, 76.1%, P < 0.001). The incidences of clinically relevant postoperative pancreatic fistula (CR-POPF) (17.0% vs. 11.1%), intra-abdominal abscess (21.0% vs. 9.1%) were significantly lower in the sequentially-checked group (all P < 0.05). Multivariate analysis revealed that use of the sequentially-checked criteria was significantly associated with CR-POPF (odds ratio 0.601, 95% confidence interval [CI] 0.389-0.929; P = 0.022). C-reactive protein <15 mg/dl at POD 3 was identified as an independent predictive factor for false positive CR-POPF results in the sequentially-checked group (odds ratio 0.872, 95% CI 0.811-0.939; P < 0.001); thus, this criterion was added to create the new triple-checked criteria. CONCLUSIONS: The sequentially-checked criteria can provide safe drain management and improve postoperative outcomes.

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.

Assessment of clinical outcome of cholecystectomy according to age in preparation for the "Silver Tsunami".

BACKGROUND: Recent rapid increases in the aging population have created an impending "Silver Tsunami" in advanced countries. The overall prevalence of gallstone disease and its related complications will soon increase, and there will be a larger demand for gallbladder surgery. METHODS: We examined the outcomes of cholecystectomy according to age among patients with cholelithiasis to determine how a patient's age influences the outcome of cholecystectomy. All patients with gallstone disease who presented for cholecystectomy at our institute from January 2006 to December 2018 were analyzed. RESULTS: All perioperative outcomes (operation length, length of hospital stay, rate of open surgery, urgent surgery, postoperative complications, incidental gallbladder cancer, postoperative hospital death, concomitant bile duct stones, and total medical costs per patient) increased as patients aged. CONCLUSIONS: To prevent the progression of biliary disease, elective laparoscopic cholecystectomy is recommended before patients with cholelithiasis advance in age.

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.