Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC. METHODS: EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups. RESULTS: Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016).　 Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively). CONCLUSION: Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.

Impact of radiological and pathological splenic vein involvement in patients with resectable pancreatic body or tail cancer.

PURPOSE: Several studies have reported a negative impact on survival associated with splenic vessel involvement, especially splenic artery (SpA) involvement, in patients diagnosed with pancreatic body or tail cancer. However, there is limited research on splenic vein (SpV) involvement. Therefore, we aimed to elucidate the significance of splenic vessel involvement, especially SpV involvement, in patients with resectable pancreatic body or tail cancer. METHODS: Between January 2007 and December 2021, 116 consecutive patients underwent distal pancreatectomies for pancreatic body or tail cancer. Among them, this study specifically examined 88 patients with resectable pancreatic body or tail cancer to elucidate prognostic factors using a multivariable Cox proportional analysis. The Kaplan-Meier method evaluated the impact of SpV involvement in terms of both radiological and pathological aspects and the efficacy of neoadjuvant therapy. RESULTS: Higher pre-operative carcinoembryonic antigen levels, larger tumour size, pathological SpV invasion, and non-completion of adjuvant therapy were identified as independent poor prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Additionally, patients with radiological SpV encasement had significantly worse prognoses in terms of OS (p = 0.039) and RFS (p < 0.001). The sensitivity and specificity of multidetector-row computed tomography for detecting pathological SpV invasion were 81.0% and 61.2%, respectively. However, the prognostic impact of neoadjuvant therapy could not be determined, regardless of radiological SpV involvement. CONCLUSION: Radiological and pathological SpV involvement is a poor prognostic factor for patients with resectable pancreatic body or tail cancer. New innovative treatments and effective neoadjuvant therapy regimens are required for patients with SpV involvement.

Radiomics-based prediction of nonalcoholic fatty liver disease following pancreatoduodenectomy.

PURPOSE: Predicting nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy (PD) is challenging, which delays therapeutic intervention and makes its prevention difficult. We conducted this study to assess the potential application of preoperative computed tomography (CT) radiomics for predicting NAFLD. METHODS: The subjects of this retrospective study were 186 patients with PD from a single institution. We extracted the predictors of NAFLD after PD statistically from conventional clinical and radiomic features of the estimated remnant pancreas and whole liver region on preoperative nonenhanced CT images. Based on these predictors, we developed a machine-learning predictive model, which integrated clinical and radiomic features. A comparative model used only clinical features as predictors. RESULTS: The incidence of NAFLD after PD was 43.5%. The variables of the clinicoradiomic model included one shape feature of the pancreas, two texture features of the liver, and sex; the variables of the clinical model were age, sex, and chemoradiotherapy. The accuracy%, precision%, recall%, F1 score, and area under the curve of the two models were 75.0, 72.7, 66.7, 69.6, and 0.80; and 69.6, 68.4, 54.2, 60.5, and 0.69, respectively. CONCLUSIONS: Preoperative CT-derived radiomic features from the pancreatic and liver regions are promising for the prediction of NAFLD post-PD. Using these features enhances the predictive model, enabling earlier intervention for high-risk patients.

Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

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

Safety and efficacy of neoadjuvant chemotherapy based on our resectability criteria for locally advanced perihilar cholangiocarcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study evaluated the safety and efficacy of NAC for PHC. METHODS: Ninety-one PHC patients without metastases were treated at our department. Patients were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC patients without regional lymph node metastases (LNM) or those unable to tolerate NAC. The NAC regimen comprised two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. RESULTS: US and NAC were performed on 32 and 59 patients, respectively. For US, 31 patients underwent curative intent surgery (upfront-CIS). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo curative intent surgery (NAC-CIS) without impairing liver function, and spared 23/59 (39%) from undergoing resection (NAC-UR). Overall survival was better in the upfront-CIS and NAC-CIS groups than in the NAC-UR group (MST: 74 vs 57 vs 17 months, p < 0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was the highest in the LA group (27% [3/11] than in R, 30% [10/33] in BR, and 67% [10/15] in LA, p = 0.039). Multivariate analyses revealed that LA and age were independent risk factors for non-resection after NAC. CONCLUSION: was safe and contributed to improving survival in advanced PHC patients. R-PHC was responsive to NAC, but LA remains a risk factor for non-resection through NAC.

Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma.

BACKGROUND: The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). RESULTS: PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). CONCLUSION: These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.

Surgical outcomes of the Frey procedure for chronic pancreatitis: correlation between preoperative characteristics and the histological severity of pancreatic fibrosis.

PURPOSE: To evaluate the efficacy of the Frey procedure and clarify the relationship between preoperative characteristics and the histological severity of chronic pancreatitis (CP). METHODS: Thirty patients who underwent the Frey procedure for CP between January, 2002 and December, 2020, at our hospital, were enrolled in this study. The specimen cored out of the pancreatic head was assessed for CP severity. We evaluated preoperative status and surgical outcomes according to CP severity. RESULTS: Long-term pain relief was achieved in all 26 patients with sustained long-term follow-up, with complete pain relief attained in 19 (63%). Albumin levels were significantly higher 1 year postoperatively than preoperatively (p = 0.038). Histological fibrosis was assessed in the 26 patients as follows: normal (n = 4; 15%), mild (n = 8; 31%), moderate (n = 2; 8%), and severe (n = 12; 46%). These patients were divided into two groups according to the severity of fibrosis: normal/mild (n = 12) and moderate/severe (n = 14). The rates of diffuse calcification on preoperative computed tomography (CT) (71% vs. 17%, p = 0.008) and islet atrophy on insulin immunohistochemistry (100% vs. 33%, p < 0.001) were significantly higher in the moderate/severe group than in the normal/mild group. CONCLUSION: The Frey procedure can achieve good pain relief and improve nutritional status. The severity of fibrosis can be predicted based on the extent of calcification on preoperative imaging studies.

Anterior versus posterior radical antegrade modular pancreatosplenectomy for pancreatic body and tail cancer: an inverse probability of treatment weighting with survival analysis.

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) is a standard procedure for patients with pancreatic body and tail cancer. There are two types of RAMPS: anterior and posterior, but their indications and surgical outcomes remain unclear. We compared the surgical outcomes, postoperative course, and prognosis between anterior and posterior RAMPS. METHODS: Between 2007 and 2020, 105 consecutive patients who underwent RAMPS for pancreatic body and tail cancers were divided into an anterior RAMPS group (n = 30) and a posterior RAMPS group (n = 75). To adjust for differences in preoperative characteristics and intraoperative procedures, an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. RESULTS: After IPTW adjustment, the postoperative body temperature of the posterior RAMPS group and the amount of drain discharge in the anterior RAMPS group were significantly lower, from postoperative days (PODs) 1 to 3, but there were no differences in postoperative complications, recurrence patterns, or prognosis between the two groups. Regarding the diagnostic ability of multidetector-row computed tomography (MD-CT) for direct tumor involvement of the left adrenal gland, the sensitivity and specificity were 100% and 90.0%, respectively. CONCLUSION: Pancreatic body and tail cancer without apparent preoperative direct tumor involvement of the left adrenal gland on MD-CT may be sufficient indication for anterior RAMPS.

Extrapancreatic extension is a better adverse prognostic factor than tumor size in patients with localized pancreatic ductal adenocarcinoma treated with chemoradiotherapy - comparison of T category between the American Joint Committee on Cancer and Japan Pancreas Society.

BACKGROUND: T category classification for pancreatic ductal adenocarcinoma (PDAC) in the Classification of Pancreatic Cancer by the Japan Pancreas Society (JPS) is quite different from that of the American Joint Committee on Cancer (AJCC). The JPS classification focuses on extrapancreatic extension, while the AJCC focuses mainly on tumor size. This study aimed at identifying prognostic factors in PDAC patients undergoing chemoradiotherapy (CRT) by comparing the differences of T categories in these two classifications. METHODS: This retrospective study involved 344 PDAC patients who underwent CRT from 2005 to 2019 and their T-category variables were re-evaluated on computed tomography (CT) images. Disease-specific survival (DSS) was compared based on the JPS and AJCC T categories, while multivariate analysis was performed to identify prognostic factors. RESULTS: Based on the AJCC, 5-year DSS of T3 was better than those of T1 and T2 (57.1% vs. 47.7% and 37.4%). In multivariate analysis, performance status, CEA, the involvement of superior mesenteric vein and superior mesenteric artery, the JPS stage before CRT, and regimen of chemotherapy were identified as independent prognostic factors. CONCLUSIONS: In localized PDAC patients treated with chemoradiotherapy, extrapancreatic extension, as while as biological, conditional and therapeutic factors, is a better prognostic factor than tumor size.

Role of Serum Carcinoma Embryonic Antigen (CEA) Level in Localized Pancreatic Adenocarcinoma: CEA Level Before Operation is a Significant Prognostic Indicator in Patients With Locally Advanced Pancreatic Cancer Treated With Neoadjuvant Therapy Followed by Surgical Resection: A Retrospective Analysis.

OBJECTIVE: The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC. SUMMARY OF BACKGROUND DATA: Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered. MATERIALS AND METHOD: From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control. RESULTS: In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor. CONCLUSIONS: CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

The usefulness of modified splenic hilum hanging maneuver in laparoscopic splenectomy, especially for patients with huge spleen: a case-control study with propensity score matching.

BACKGROUND: Although Laparoscopic splenectomy (LS) have been proven to the standard operation for removal of spleen, the rate of conversion to open surgery is still higher than those of other laparoscopic surgeries, especially for huge spleen. In order to reduce the rate of conversion to open surgery, we had developed LS using modified splenic hilum hanging (MSHH) maneuver: the splenic pedicle was transected en bloc using a surgical stapler after hanging splenic hilum with an atraumatic penrose drain tube. METHODS: Between January 2005 and December 2019, we retrospectively assessed 94 patients who underwent LS. MSHH maneuver was performed in 37 patients (39.4%). We compared the intra- and postoperative outcomes between patients with or without MSHH maneuver. To adjust for differences in preoperative characteristics and blood examination, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 29 patients per group. Predictive factors of conversion from LS to open surgery were elucidated using the uni- and multi-variate analyses. RESULTS: After the propensity score matching, blood loss (268 ml vs. 50 ml), the rate of conversion to open surgery (27.6% vs. 0%), and postoperative hospital stays (15 days vs. 10 days) were significantly decreased in patients with MSHH maneuver, respectively. Among 94 patients, 19 patients (20.2%) underwent conversion to open surgery. In multivariate analysis, spleen volume (SV) and LS without MSHH maneuver were independent predictive factors of conversion to open surgery, respectively. Additionally, cut-off value of SV for conversion to open surgery was 802 ml (sensitivity: 0.684, specificity: 0.827, p < 0.001). CONCLUSIONS: LS using MSHH maneuver seems to be useful surgical technique to improve intraoperative outcomes and reduce the rate of conversion from LS to open surgery resulting in shorten postoperative hospital stay.

Resection type is a predictor of postoperative complications in laparoscopic partial liver resection.

BACKGROUND: Partial laparoscopic liver resection (LLR) is a procedure that can have varying levels of surgical difficulty depending on the tumor status and procedure. Therefore, we aimed to evaluate the surgical outcomes of partial LLR using a new resection classification system. METHODS: From January 2009 to May 2021, 156 patients underwent LLR; of them, 87 patients who underwent pure partial LLR were included in this study. They were classified according to the IWATE criteria as the low (n = 56) and intermediate (n = 31) difficulty groups and reclassified according to the resection type as the edge (ER, n = 45), bowl-shaped (BSR, n = 27), and dome-shaped resection (DSR, n = 15) groups. The following surgical outcomes were comparatively analyzed among the groups: intraoperative blood loss, the operation time, and complication rates. Preoperative risk factors for intraoperative blood transfusion and complications were evaluated. RESULTS: In the IWATE criteria-based analysis, the intermediate-difficulty group had significantly higher intraoperative blood loss (p = 0.005), operation time (p = 0.005), and Clavien-Dindo (CD) grade-based complication rates (CD grade 2 or higher, p = 0.03) than the low-difficulty group. When analyzing the resection type, the CD grade-based complication rate (p = 0.013) and surgical site infection (SSI, p = 0.005) were significantly higher and the postoperative hospitalization was significantly longer (p = 0.028) in the bowl-shaped resection (BSR) group than in the edge- (ER) and dome-shaped resection (DSR) groups. The tumor size (p = 0.011) and IWATE criteria score (p = 0.006) were independent risk factors for intraoperative blood transfusion in the multivariate analysis. The tumor depth (p = 0.011) and BSR (p = 0.002) were independent risk factors for complications of CD grade 2 or higher in the multivariate analysis. BSR was an independent risk factor for SSI in the multivariate analysis (p = 0.017). CONCLUSIONS: Resection type could predict the rate of postoperative complications, while the IWATE criteria could predict the intraoperative surgical difficulty.

Safety and benefits of major hepatectomy with extrahepatic bile duct resection in older perihilar cholangiocarcinoma patients.

PURPOSE: To evaluate the safety and benefits of major hepatectomy with extrahepatic bile duct resection in older perihilar cholangiocarcinoma patients and to identify possible predictors of surgical mortality. METHODS: We retrospectively analyzed the data of 102 consecutive patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma in our institution between 2004 and 2021. The patients were included and divided into two groups: older patients ≥ 75 years and non-older patients < 75 years. Patient characteristics, preoperative nutritional and operative risk scores, intraoperative details, postoperative outcomes, and long-term prognosis were compared between the groups. Univariate and multivariate analyses were used to identify the predictors of 90-day mortality after major hepatectomy with extrahepatic bile duct resection. RESULTS: Significant differences were identified for some preoperative surgical risk scores, but not for nutritional scores. Older patients had a higher morbidity rate of respiratory complications (p = 0.016), but there were no significant differences in overall (p = 0.735) or disease-specific survival (p = 0.858). A high Dasari's score was identified as an independent predictive factor of 90-day mortality. CONCLUSIONS: Major hepatectomy with extrahepatic bile duct resection can be performed for optimally selected older and younger patients with perihilar cholangiocarcinoma, resulting in a good prognosis. However, indications for extended surgery should be recognized. Dasari's preoperative risk score may be a good predictor of 90-day mortality.

Risk factor analysis of postoperative pancreatic fistula after distal pancreatectomy, with a focus on pancreas-visceral fat CT value ratio and serrated pancreatic contour.

BACKGROUND: In pancreaticoduodenectomy, the pancreas-visceral fat CT value ratio and serrated pancreatic contour on preoperative CT have been revealed as risk factors for postoperative pancreatic fistulas. We aimed to evaluate whether they could also serve as risk factors for postoperative pancreatic fistulas after distal pancreatectomy. METHODS: A total of 251 patients that underwent distal pancreatectomy at our department from 2006 to 2020 were enrolled for the study. We retrospectively analyzed risk factors for postoperative pancreatic fistulas after distal pancreatectomy using various pre and intraoperative factors, including preoperative CT findings, such as pancreas-visceral fat CT value ratio and serrated pancreatic contour. RESULTS: The study population included 147 male and 104 female participants (median age, 68 years; median body mass index, 21.4 kg/m2), including 64 patients with diabetes mellitus (25.5%). Preoperative CT evaluation showed a serrated pancreatic contour in 80 patients (31.9%), a pancreatic thickness of 9.3 mm (4.0-22.0 mm), pancreatic parenchymal CT value of 41.8 HU (4.3-22.0 HU), and pancreas-visceral fat CT value ratio of - 0.41 (- 4.88 to - 0.04). Postoperative pancreatic fistulas were developed in 34.2% of the patients. Univariate analysis of risk factors for postoperative pancreatic fistulas showed that younger age (P = 0.005), high body mass index (P = 0.001), absence of diabetes mellitus (P = 0.002), high preoperative C-reactive protein level (P = 0.024), pancreatic thickness (P < 0.001), and high pancreatic parenchymal CT value (P = 0.018) were significant risk factors; however, pancreas-visceral fat CT value ratio (P = 0.337) and a serrated pancreatic contour (P = 0.122) did not serve as risk factors. Multivariate analysis showed that high body mass index (P = 0.032), absence of diabetes mellitus (P = 0.001), and pancreatic thickness (P < 0.001) were independent risk factors. CONCLUSION: The pancreas-visceral fat CT value ratio and serrated pancreatic contour evaluated using preoperative CT were not risk factors for postoperative pancreatic fistulas after distal pancreatectomy. High body mass index, absence of diabetes mellitus, and pancreatic thickness were independent risk factors, and a close-to-normal pancreas with minimal fat deposition or atrophy is thought to indicate a higher risk of postoperative pancreatic fistulas after distal pancreatectomy.

Left-sided Portal Hypertension After Pancreaticoduodenectomy With Resection of the Portal Vein/Superior Mesenteric Vein Confluence in Patients With Pancreatic Cancer: A Project Study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

OBJECTIVE: The aim of this study was to evaluate how often left-sided portal hypertension (LPH) develops and how LPH affects the long-term outcomes of patients with pancreatic cancer treated with pancreaticoduodenectomy (PD) and resection of the portal vein (PV)/superior mesenteric vein (SMV) confluence. SUMMARY BACKGROUND DATA: Little is known about LPH after PD with resection of the PV/SMV confluence. METHODS: Overall, 536 patients who underwent PD with PV/SMV resection were enrolled. Among them, we mainly compared the SVp group [n=285; the splenic vein (SV) was preserved] and the SVr group (n = 227; the SV was divided and not reconstructed). RESULTS: The incidence of variceal formation in the SVr group increased until 3 years after PD compared with that in the SVp group (38.7% vs 8.3%, P < 0.001). Variceal bleeding occurred in the SVr group (n = 9: 4.0%) but not in the SVp group (P < 0.001). In the multivariate analysis, the risk factors for variceal formation were liver disease, N factor, conventional PD, middle colic artery resection, and SV division. The only risk factor for variceal bleeding was SV division. The platelet count ratio at 6 months after PD was significantly lower in the SVr group than in the SVp group (0.97 vs 0.82, P < 0.001), and the spleen-volume ratios at 6 and 12 months were significantly higher in the SVr group than in the SVp group (1.38 vs 1.00 and 1.54 vs 1.09; P < 0.001 and P < 0.001, respectively). CONCLUSIONS: PD with SV division causes variceal formation, bleeding, and thrombocytopenia.

The Impact of Dabigatran Treatment on Sinusoidal Protection Against Hepatic Ischemia/Reperfusion Injury in Mice.

Thrombin is a key player in the coagulation cascade, and it is attracting much attention as a promotor of cellular injured signaling. In ischemia/reperfusion injury (IRI), which is a severe complication of liver transplantation, thrombin may also promote tissue damage. The aim of this study is to reveal whether dabigatran, a direct thrombin inhibitor, can attenuate hepatic IRI with focusing on a protection of sinusoidal endothelial cells (SECs). Both clinical patients who underwent hepatectomy and in vivo mice model of 60-minute hepatic partial-warm IRII, thrombin generation was evaluated before and after IRI. In next study, IRI mice were treated with or without dabigatran. In addition, hepatic SECs and hepatocytes pretreated with or without dabigatran were incubated in hypoxia/reoxygenation (H-R) environment in vitro. Thrombin generation evaluated by thrombin-antithrombin complex (TAT) was significantly enhanced after IRI in the clinical study and in vivo study. Thrombin exacerbated lactate dehydrogenase cytotoxicity levels in a dose-dependent manner in vitro. In an IRI model of mice, dabigatran treatment significantly improved liver histological damage, induced sinusoidal protection, and provided both antiapoptotic and anti-inflammatory effects. Furthermore, dabigatran not only enhanced endogenous thrombomodulin (TM) but also reduced excessive serum high-mobility group box-1 (HMGB-1). In H-R models of SECs, not hepatocytes, pretreatment with dabigatran markedly attenuated H-R damage, enhanced TM expression in cell lysate, and decreased extracellular HMGB-1. The supernatant of SECs pretreated with dabigatran protected hepatocytes from H-R damage and cellular death. Thrombin exacerbated hepatic IRI, and excessive extracellular HMGB-1 caused severe inflammation-induced and apoptosis-induced liver damage. In this situation, dabigatran treatment improved vascular integrity via sinusoidal protection and degraded HMGB-1 by endogenous TM enhancement on SECs, greatly ameliorating hepatic IRI.

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined. OBJECTIVE: To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC. METHODS: The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis. RESULTS: Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR. CONCLUSIONS: pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.

Biliary peritonitis due to liver cyst rupture in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic kidney disease and polycystic liver disease is its major extrarenal manifestation, however biliary peritonitis due to a liver cyst rupture is extremely rare. CASE PRESENTATION: The patient was a 71-year-old Japanese woman who was diagnosed with ADPKD 3 years previously and developed right abdominal pain suddenly 1 month previously. As abdominal computed tomography (CT) showed a ruptured liver cyst in the right lobe, she was admitted to our hospital. Her symptoms improved with conservative management and she was discharged from the hospital after 1 week. Although she was asymptomatic for a while, she noticed abdominal distension and general malaise at 1 month after hospital discharge. Since abdominal CT showed massive ascites, she was admitted to our hospital again. A physical examination revealed abdominal distention without tenderness. Her serum creatinine, alkaline phosphatase, γ-glutamyl transpeptidase, total bilirubin, and CA19-9 were elevated. Abdominal paracentesis revealed amber transparent ascites and the bilirubin and CA19-9 concentrations were high. She was diagnosed with biliary peritonitis due to a ruptured liver cyst. Hemodialysis treatment was initiated with drainage of the ascites. The outflow of the ascites was no tendency to decrease and drip infusion cholangiography (DIC)-CT revealed a communication between the ruptured cyst and an intrahepatic bile duct. On day 31, she was transferred to a university hospital and abdominal surgery was performed. After removing the necrotic roof of the ruptured cyst on the right liver lobe, the orifice of the bile leakage was sutured. Cholecystectomy was performed and cholangiography showed no stones in the common bile duct. Abdominal CT one month after the operation showed no recurrence of ascites and she was discharged on day 49. Hemodialysis treatment was discontinued immediately after discharge because urine volume increased and her creatinine level decreased. There has been no recurrence of ascites since then. CONCLUSIONS: While rare, biliary peritonitis can occur in association with the rupture of a liver cyst in ADPKD patients due to communication between the cyst and the intrahepatic bile duct, and DIC-CT should be recommended when biliary cyst rupture is suspected.

Association between gastric Candida colonization and surgical site infections after high-level hepatobiliary pancreatic surgeries: the results of prospective observational study.

AIM: High-level hepatobiliary pancreatic (HBP) surgeries are highly associated with surgical site infections (SSIs), in which microorganisms have a significant role. In the present study, we investigated whether gastric Candida colonization had a significant role in SSIs after high-level HBP surgeries. METHODS: Between May 2016 and February 2017, the 66 patients who underwent high-level HBP surgeries were enrolled in the present study. The gastric juice was prospectively collected through nasogastric tube after general anesthesia induction and was incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. First of all, we compared the incidence of SSIs according to the presence or absence of Candida species in gastric juice. Secondly, we evaluated the variables contributing to the development of SSIs by multivariate analysis. The protocol was approved by the medical ethics committee of Mie University Hospital (No.2987). RESULTS: Gastric Candida colonization was identified in 21 patients (group GC) and was not identified in the other 45 patients (group NGC). There were no differences in preoperative variables including compromised status, such as age, nutritional markers, complications of diabetes mellitus, and types of primary disease between the two groups. SSIs occurred in 57.1% (12/21) of group GC and in 17.8% (8/45) of group NGC, showing a significant difference (p = 0.001). Multivariate analysis revealed gastric Candida colonization as a significant risk factor of SSIs (OR 6.17, p = 0.002). CONCLUSION: Gastric Candida colonization, which is not a result of immunocompromised status, is highly associated with SSIs after high-level HBP surgeries. TRIAL REGISTRATION: Japan Primary Registries Network; UMIN-CTR ID: UMIN000040486 (retrospectively registered on 22nd May, 2020).