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.

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.

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.

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.

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.

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).

Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy-Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma.

The present study was conducted to determine whether active hexose correlated compound (AHCC), a functional food extracted from cultured basidiomycetes, possesses the potential to attenuate adverse events in unresectable pancreas ductal adenocarcinoma (PDAC) patients receiving chemotherapy. Unresectable PDAC patients receiving gemcitabine treatment (GEM) as the first-line chemotherapy were prospectively divided into 2 groups according to AHCC intake (AHCC group, n = 35) or not (control group, n = 40). The patients in the AHCC group ingested 6.0 g of AHCC for 2 mo. Hematological and nonhematological toxicity was compared between the AHCC and control groups. The C-reactive protein (CRP) elevation and albumin decline of the AHCC group were significantly suppressed as compared to the control group during the GEM administration (P = 0.0012, P = 0.0007). Patients in the AHCC group had less frequency of taste disorder caused by GEM (17% vs. 56%, P = 0.0007). Frequency of grade 3 in the modified Glasgow Prognostic Score (mGPS) during chemotherapy was found significantly less in the AHCC group (14%) than the control group (53%, P = 0.0005). AHCC intake can be effective in reducing the adverse events associated with chemotherapy and may contribute to maintaining the QOL of patients with PDAC during GEM administration.

A clinical role of staging laparoscopy in patients with radiographically defined locally advanced pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of current study is to verify usefulness of staging laparoscopy (stag-lap) for patient's selection and to find prognostic factors in patients with radiographically defined locally advanced (RD-LA) pancreatic ductal adenocarcinoma (PDAC). METHODS: The LA disease was defined as an unresectable disease without distant organ metastasis based on resectability status of NCCN guideline in this study. Stag-lap was performed in 67 patients with RD-LA (2007-2012) which were divided into 4 groups according to metastatic site: group CY (peritoneal fluid or washing cytology positive and without any distant organ metastasis); group P (peritoneal dissemination); group L (liver metastasis); group LA (peritoneal fluid or washing cytology negative and without any distant organ metastasis). Clinical backgrounds, survival curves, and prognostic factors were investigated. RESULTS: There were 16 patients in CY group (24%), 13 patients in P group (19%), 10 patients in L group (15%), and 28 patients in LA group (42%). Median survival time was 13 months in CY group and 11 months in LA group, which was significantly better than 7 months in P group, respectively (p<0.05). The rate of emergence of ascites in LA was significantly better than in CY or P groups (p<0.05). Multivariate analysis showed that the presence of partial response and administration of second-line chemotherapy were significantly independent prognostic factors. CONCLUSIONS: The majority of PDAC patients with RD-LA had occult distant organ metastasis. Clinical features and survival curves were different depending on the site of occult distant organ metastasis. Administration of second-line chemotherapy and responsiveness to chemotherapy were associated with favorable prognosis. Staging laparoscopy should be routinely performed in patients with RD-LA PDAC (UMIN000019936).

Potential role of surgical resection for pancreatic cancer in the very elderly.

BACKGROUND: There is increasing need to evaluate the surgical indication of pancreatic cancer in very elderly patients. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of pancreatic resection in pancreatic cancer patients over the age of 80. METHODS: Between 2005 and 2012, 26 octogenarian patients who received pancreatic resection and 20 who received chemotherapy for pancreatic cancer were retrospectively reviewed. Clinicopathological factors, chemotherapy administration status, and survival were compared. Univariate and multivariate analysis of prognostic factors for survival was performed. RESULTS: Postoperative major complication rate was 8%, with no mortality. The one-year survival rate and median survival time of the surgery and chemotherapy groups were 50% and 45%, and 12.4 months and 11.7 months, respectively (P = 0.263). Of the 26 resected cases, 6 completed the planned adjuvant chemotherapy treatment course. The median survival time of those 6 completed cases was significantly longer than that of the 20 not completed cases (23.4 versus 10.0 months, P = 0.034). Furthermore, a multivariate analysis of the 26 resected cases showed that distant metastasis (HR 3.206, 95%CI 1.005-10.22, P = 0.049) and completion of the planned adjuvant therapy (HR 4.078, 95%CI 1.162-14.30, P = 0.028) were independent prognostic factors of surgical resection. CONCLUSIONS: Surgical resection was safe, but not superior to chemotherapy for pancreatic cancer in octogenarians. In the very elderly, only selected patients may benefit from pancreatic resection.

Laparoscopic distal pancreatectomy for a pancreatic lymphoepithelial cyst: case report and review of literature.

CONTEXT: Lymphoepithelial cysts of the pancreas are a rare disease of true pancreatic cysts, the cause of which is unknown. The differential diagnosis is broad and includes many benign and malignant cystic lesions of the pancreas and surrounding organs. A combination of imaging modalities and fine needle aspiration might narrow the differential diagnosis. However, the final diagnosis can only be achieved with certainty after resection of the cyst. CASE REPORT: The present case report is a lymphoepithelial cyst of the pancreas that was resected laparoscopically. A 53-year-old man was incidentally found to have a cystic tumor in the tail of the pancreas after undergoing an abdominal ultrasound, which showed a 41x33 mm cystic mass in the pancreatic tail. He had no abdominal symptoms. Laparoscopic distal pancreatectomy and splenectomy were performed. Histologic examination revealed a lymphoepithelial cyst. CONCLUSION: Herein, we discuss the diagnostic difficulties and management decisions that face surgeons treating pancreatic cysts.

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.

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.

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.

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.

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.