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.

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.

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.

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).

Proximal subtotal pancreatectomy as an alternative to total pancreatectomy for malnourished patients.

PURPOSE: To investigate whether proximal subtotal pancreatectomy (PSTP) is superior to total pancreatectomy (TP) for preserving postoperative endocrine function, and to identify the pre-operative risk factors influencing prognosis after TP and PSTP. METHODS: The subjects of this retrospective study were patients who underwent TP (n = 15) or PSTP (n = 16) between 2008 and 2018 in our hospital. First, we compared the incidence of hypoglycemia within 30 days after surgery and the total daily amount of insulin needed in the 30 days after TP vs. PSTP. Then, we compared the prognoses between the groups. RESULTS: The incidence of hypoglycemia in the 30 days after surgery was significantly lower in the PSTP group than in the TP group (n = 0 vs. n = 5; p < 0.001). The total amount of daily insulin given was also significantly lower after PSTP than after TP: (0 units vs. 18 units, p = 0.001). Lower lymphocyte counts (p = 0.014), lower cholinesterase (p = 0.021), and lower prognostic nutrition index (p = 0.021) were identified as significant risk factors for hypoglycemia in the TP group. Low cholinesterase (p = 0.015) and a low prognostic nutrition index (p = 0.048) were significantly associated with an unfavorable prognosis in the TP group, but not in the PSTP group. CONCLUSIONS: PSTP may be a feasible alternative to TP to preserve endocrine function, especially for malnourished patients.

Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status.

BACKGROUND: The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. METHODS: Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. RESULTS: Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. CONCLUSION: Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection.

BACKGROUND: Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. METHODS: Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). RESULTS: In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). CONCLUSION: This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

Prolonged operating time is a significant perioperative risk factor for arterial pseudoaneurysm formation and patient death following hemorrhage after pancreaticoduodenectomy.

BACKGROUND: Arterial pseudoaneurysm is a rare but potentially fatal complication after pancreaticoduodenectomy (PD). This study aimed to evaluate the incidence and predictors associated with pseudoaneurysm formation and patient death caused by its rupture. PATIENTS AND METHOD: We retrospectively reviewed the data of 453 patients who underwent PD from April 2007 to February 2019. Uni- and multivariate analysis and receiver operating characteristic (ROC) curve analysis were performed to identify risk factors and optimal cutoff values. RESULTS: Among the 453 patients, 22 (4.9%) developed pseudoaneurysm after PD. Median duration from surgery to detection of pseudoaneurysm was 17.0 (1-51) days. The locations of pseudoaneurysms were hepatic artery in 8, splenic artery in 3, gastroduodenal artery in 4, gastric artery in 2 and others in 5 patients, and 72.7% (16/22) of patients presented with hemorrhage. All pseudoaneurysms were treated using angioembolization. Lower age (<65.5 years, p = 0.004), prolonged operation time (Cutoff ˃610 min, p = 0.026) and postoperative pancreatic fistula (POPF) (p = 0.013) were the independent risk factors for development of pseudoaneurysm. 6 (27.3%) patients died due to rupture of pseudoaneurysm and prolonged operation time (Cutoff ˃657 min, p = 0.043) was a significant risk factor for death related to pseudoaneurysm. CONCLUSION: Prolonged operating time was identified as a risk factor for both pseudoaneurysm formation and patient death following pseudoaneurysm bleeding. Interventional radiology treatment offered a central role in the treatment of pseudoaneurysms after PD. Therefore, it is important to have a high index of suspicion in high risk patients of the possibility of pseudoaneurysm formation and bleeding.

Antiapoptotic Effect by PAR-1 Antagonist Protects Mouse Liver Against Ischemia-Reperfusion Injury.

BACKGROUND: Coagulation disturbances in several liver diseases lead to thrombin generation, which triggers intracellular injury via activation of protease-activated receptor-1 (PAR-1). Little is known about the thrombin/PAR-1 pathway in hepatic ischemia-reperfusion injury (IRI). The present study aimed to clarify whether a newly selective PAR-1 antagonist, vorapaxar, can attenuate liver damage caused by hepatic IRI, with a focus on apoptosis and the survival-signaling pathway. METHODS: A 60-min hepatic partial-warm IRI model was used to evaluate PAR-1 expression in vivo. Subsequently, IRI mice were treated with or without vorapaxar (with vehicle). In addition, hepatic sinusoidal endothelial cells (SECs) pretreated with or without vorapaxar (with vehicle) were incubated during hypoxia-reoxygenation in vitro. RESULTS: In naïve livers, PAR-1 was confirmed by immunohistochemistry and immunofluorescence analysis to be located on hepatic SECs, and IRI strongly enhanced PAR-1 expression. In IRI mice models, vorapaxar treatment significantly decreased serum transaminase levels, improved liver histological damage, reduced the number of apoptotic cells as evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (median: 135 versus 25, P = 0.004), and induced extracellular signal-regulated kinase 1/2 (ERK 1/2) cell survival signaling (phospho-ERK/total ERK 1/2: 0.96 versus 5.34, P = 0.004). Pretreatment of SECs with vorapaxar significantly attenuated apoptosis and induced phosphorylation of ERK 1/2 in vitro (phospho-ERK/total ERK 1/2: 0.66 versus 3.04, P = 0.009). These changes were abolished by the addition of PD98059, the ERK 1/2 pathway inhibitor, before treatment with vorapaxar. CONCLUSIONS: The results of the present study revealed that hepatic IRI induces significant enhancement of PAR-1 expression on SECs, which may be associated with suppression of survival signaling pathways such as ERK 1/2, resulting in severe apoptosis-induced hepatic damage. Thus, the selective PAR-1 antagonist attenuates hepatic IRI through an antiapoptotic effect by the activation of survival-signaling pathways.

Onodera's prognostic nutritional index is a strong prognostic indicator for patients with hepatocellular carcinoma after initial hepatectomy, especially patients with preserved liver function.

BACKGROUND: Several inflammation-based scores are used to assess the surgical outcomes of hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the prognostic value of the prognostic nutritional index (PNI) in HCC patients who underwent hepatectomy with special attention to preoperative liver functional reserve. METHODS: Preoperative demographic and tumor-related factors were analyzed in 189 patients with HCC undergoing initial hepatectomy from August 2005 to May 2016 to identify significant prognostic factors. RESULTS: Multivariate analysis for overall survival (OS) revealed that female sex (p = 0.005), tumor size (p < 0.001) and PNI (p = 0.001) were independent prognostic factors. Compared to the High PNI group (PNI ≥ 37, n = 172), the Low PNI group (PNI < 37, n = 17) had impaired liver function and significantly poorer OS (13% vs. 67% in 5-year OS, p = 0.001) and recurrence-free survival (RFS) (8 vs. 25 months in median PFS time, p = 0.002). In the subgroup of patients with a preserved liver function of LHL15 ≥ 0.9, PNI was also independent prognostic factor, and OS (21% vs. 70% in 5-year OS, p = 0.008) and RFS (8 vs. 28 months in median PFS time, p = 0.018) were significantly poorer in the Low PNI group than the High PNI group. CONCLUSIONS: PNI was an independent prognostic factor for HCC patients who underwent hepatectomy. Patients with PNI lower than 37 were at high risk for early recurrence and poor patient survival, especially in the patients with preserved liver function of LHL ≥ 0.9.

Pancreas-visceral fat CT value ratio and serrated pancreatic contour are strong predictors of postoperative pancreatic fistula after pancreaticojejunostomy.

BACKGROUND: Our aim is to elucidate the true preoperative risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), making it possible to select POPF high-risk patients preoperatively regardless of intraoperative pancreatic consistency judged by the surgeon's hand. METHODS: Among the 298 patients who underwent PD with pancreaticojejunostomy from 2007 to 2016, 262 patients had preoperative CT configurations that could be precisely evaluated. Risk factor analyses were conducted using various perioperative factors, including preoperative CT findings, such as CT values of the pancreas, pancreas-visceral fat CT value ratio and pancreatic outer contour. Pancreatic outer contour was further divided into smooth- (smooth interlobular) and serrated-type contours (feathery, irregular interlobular) by preoperative CT. RESULTS: In terms of the incidence of POPF, among the 262 patients, POPF grade B/C was found in 27 (10.3%): grade B in 23 (8.8%) and grade C in 4 (1.5%). According to multivariate analysis, a high pancreas-visceral fat CT value ratio (p = 0.002), serrated-type contour (p = 0.02) and no history of chemoradiotherapy (p = 0.019) were identified as independent risk factors for POPF grade B/C. Even in patients with soft pancreas, the incidence of POPF grade B/C was 0% (0/57) in patients with a pancreas-visceral fat CT value ratio of less than - 0.4 and smooth-type contour, whereas the incidence was markedly high (45.0%, 9/20) in patients with a pancreas-visceral fat CT value ratio of - 0.4 or greater and serrated-type contour, indicating that patients with soft pancreas should be categorized into POPF high-risk and low-risk groups according to preoperative CT scan results. CONCLUSIONS: The pancreas-visceral fat CT value ratio and serrated-type pancreas are useful markers to preoperatively identify true POPF high-risk groups in patients undergoing PD, regardless of the pancreatic texture judged intraoperatively.

Clinical Impact of Neoadjuvant Chemotherapy and Chemoradiotherapy in Borderline Resectable Pancreatic Cancer: Analysis of 884 Patients at Facilities Specializing in Pancreatic Surgery.

BACKGROUND: The efficacy of neoadjuvant therapy (NAT), including neoadjuvant chemotherapy (NAC) and neoadjuvant chemo-radiotherapy (NACRT), for patients with borderline resectable pancreatic cancer (BRPC) has not been elucidated. This study aimed to clarify the efficacy of NAC and NACRT for patients with BRPC. METHODS: The study analyzed the treatment outcomes of 884 patients treated for BRPC from 2011 to 2013. Treatment results were compared between upfront surgery and NAT and between NAC and NACRT using propensity score-matching analysis. Overall survival (OS) was calculated via intention-to-treat analyses. RESULTS: The overall resection rates for the patients who underwent NAT were significantly lower than for the patients who underwent upfront surgery (75.1% vs 93.3%; p < 0.001). However, the R0 resection rate was significantly higher for NAT than for upfront surgery (p < 0.001). Additionally, the OS for the patients who received NAT was significantly longer than for those who underwent upfront surgery (median survival time [MST], 25.7 vs 19.0 months; p = 0.015). The lymph node rate for the patients with NACRT was significantly lower than for those who underwent NAC (p < 0.001). However, the resection rate for the NACRT cases was significantly lower than for the NAC cases (p = 0.041). The local recurrence rate for the NACRT cases was significantly lower than for the NAC cases (p = 0.002). However, OS did not differ significantly between NAC and NACRT (MST, 29.2 vs 22.5 months; p = 0.130). CONCLUSIONS: The study showed that NAT has potential benefit for patients with BRPC. Compared with NAC, NACRT decreased the rates for lymph node metastasis and local recurrence but did not improve the prognosis.

The clinical impact of portal venous patency ratio on prognosis of patients with pancreatic ductal adenocarcinoma undergoing pancreatectomy with combined resection of portal vein following preoperative chemoradiotherapy.

We analyzed the significance of portal vein (PV) patency ratio (minimum diameter/maximum diameter) during preoperative chemoradiotherapy (CRT) on the outcomes of patients with pancreatic-ductal adenocarcinoma (PDAC). METHODS: The 261 PDAC patients had been prospectively registered to our CRT protocol (Gemcitabine or S1+Gemcitabine) from 2005 to 2015. Among them, the subjects were the 84 PDAC- patients with preoperative PV contact who underwent pancreatectomy with PV resection. RESULTS: The 3- and 5-year disease-specific survival (DSS) rates of all 84 patients were 44% and 39%, respectively. Pathological PV invasion (pPV) was seen in 22, and PV patency ratio after CRT (cut-off:0.62) was most relevant factor to predict pPV (sensitivity:54.8%, specificity:91.9%, accuracy:81.5%). Multivariate analysis revealed that PV patency ratio after CRT and improvement of PV patency ratio were selected as independent prognostic indicators. The 3- and 5-year DSS in 39 patients with PV patency ratio after CRT >0.6 were significantly higher than those in 45 patients <0.6: 65% and 60% vs. 24% and 20% (p = 0.0001). The patients with PV patency ratio >0.6, were significantly associated with the lower incidence of pPV, higher response for CRT, and better R0 resection rate. Even when severe PV strictures were seen before CRT, DSS of the patients whose PV patency ratio had recovered after CRT was excellent compared with those without improvement. CONCLUSIONS: The PV patency ratio and its improvement are new prognostic indicators for PDAC treated with preoperative CRT. Even when PV was severely constricted, patients could obtain favorable outcomes, if its patency had recovered after CRT.

Needle tract seeding following endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer: a report of two cases.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful tool in pancreatic cancer diagnosis. However, the procedure itself may cause peritoneal dissemination and needle tract seeding at the puncture site. We herein report two cases of gastric wall metastasis due to needle tract seeding after EUS-FNA. CASE PRESENTATION: Case 1: A 68-year-old woman was admitted to our hospital for persistent cough. Computed tomography (CT) scan revealed inflammatory changes in the left lung field, and incidentally, a 15-mm hypovascular mass was detected in the pancreatic body. She underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. She underwent distal pancreatectomy with splenectomy; however, a small hard mass was observed in the posterior gastric wall during surgery. We performed partial gastrectomy, and the resected specimen was diagnosed as a needle tract seeding following EUS-FNA. She then underwent adjuvant chemotherapy with TS-1, but the pancreatic cancer showed recurrence 6 months after surgery. She died due to peritoneal dissemination 18 months after surgery. Case 2: A 70-year-old man was incidentally detected with a pancreatic body mass on a CT scan as part of his follow-up for recurrence of basal cell carcinoma. He underwent EUS-FNA and was diagnosed as pancreatic adenocarcinoma. He had nodules in both lungs, and it was difficult to differentiate them from lung metastasis of pancreatic cancer. Therefore, he underwent neoadjuvant chemoradiotherapy, and thereafter, the lung nodules showed no changes; hence, he underwent distal pancreatectomy with splenectomy. During surgery, we observed a hard mass in the posterior gastric wall. We performed partial gastrectomy, and the resected specimen was diagnosed as needle tract seeding due to EUS-FNA. He underwent chemotherapy with TS-1, and he is still alive 18 months after surgery at the time of writing. CONCLUSION: For resectable pancreatic body or tail tumors, EUS-FNA should be carefully performed to prevent needle tract seeding and intraoperative as well as postoperative assessment for gastric wall metastasis is mandatory.

Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial.

PURPOSES: This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection. METHOD: We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI. RESULTS: Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, - 0.30; 90% CI - 4.80 to 4.19% [95% CI - 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable. CONCLUSION: To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.

International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017.

This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight issues which remain controversial and require further research.

Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury.

BACKGROUND: Functional and structural damages in sinusoidal endothelial cells (SECs) have a crucial role during hepatic ischemia-reperfusion injury (IRI). In regulating endothelial function, sphingosine-1-phosphate receptor 1 (S1PR1), which is a G protein-coupled receptor, has an important role. The present study aimed to clarify whether SEW2871, a selective S1PR1 agonist, can attenuate hepatic damage caused by hepatic IRI, focusing on SEC functions. METHODS: In vivo, using a 60-min partial-warm IRI model, mice were treated with SEW2871 or without it (with vehicle). In vitro, isolated SECs pretreated with SEW2871 or without it (with vehicle) were incubated with hydrogen peroxide. RESULTS: Compared with the IRI + vehicle group, SEW2871 administration significantly improved serum transaminase levels and liver damage, attenuated infiltration of Ly-6G and mouse macrophage antigen-1-positive cells, suppressed the expression of vascular cell adhesion molecule-1 and proinflammatory cytokines in the liver, and enhanced the expressions of endothelial nitric oxide synthase (eNOS) and vascular endothelial (VE) cadherin in the liver (eNOS/ß-actin [median]: 0.24 versus 0.53, P = 0.008; VE-cadherin/ß-actin [median]: 0.21 versus 0.94, P = 0.008). In vitro, compared with the vehicle group, pretreatment of SECs with SEW2871 significantly increased the expressions of eNOS and VE-cadherin (eNOS/ß-actin [median]: 0.22 versus 0.29, P = 0.008; VE-cadherin/ß-actin [median]: 0.38 versus 0.67, P = 0.008). As results of investigation of prosurvival signals, SEW2871 significantly increased Akt phosphorylation in SECs and decreased lactate dehydrogenase levels in supernatants of SECs. CONCLUSIONS: These results indicate that S1PR1 agonist induces attenuation of hepatic IRI, which might be provided by preventing SEC damage. S1PR1 may be a therapeutic target for the prevention of early sinusoidal injury after hepatic IRI.

A case of hepatic anisakiasis caused by Pseudoterranova decipiens mimicking metastatic liver cancer.

BACKGROUND: Anisakid nematodes (Anisakis spp. or Pseudoterranova spp.) usually infect gastric or intestinal walls, while they rarely infect in extra-gastrointestinal sites of human body. Generally, Anisakis spp. larvae are highly infected in fish intermediate hosts, whereas Pseudoterranova spp. larvae are very rarely infected. To the best of our knowledge, there have been no reports which have documented cases of hepatic anisakiasis caused by Pseudoterranova spp. This report describes the first documented case of hepatic anisakiasis due to infection with Pseudoterranova decipiens and clinical features of the hepatic anisakiasis through literature review. CASE PRESENTATION: The case was a 28-year-old man with prior history of malignancy who was found to have a hepatic mass mimicking metastatic liver tumor. A new low density area of 20 mm in diameter in liver segment 7 was found on follow-up CT. With suspicious diagnosis of metastatic liver cancer, laparoscopic partial hepatectomy was performed. A pathological examination revealed no evidence of malignancy, but showed necrotic granuloma with eosinophil infiltration and the presence of a larva with Y-shaped lateral cords, which are specific to anisakid larvae. The type of larva was identified as Pseudoterranova decipiens sensu lato using PCR of DNA purified from a fixed granuloma embedded in paraffin. CONCLUSION: The present report is the first to discuss the case of a patient with hepatic anisakiasis caused by Pseudoterranova decipiens. Hepatic anisakiasis is a potential differential diagnosis for hepatic tumors and genetic identification with the PCR method was reliable for obtaining final diagnosis even when the larvae body in the resected specimen collapses with time.

Incidence and Risk Factors of Postoperative Delirium following Pancreatic Surgery: Does the Administration of TJ-54 Reduce the Incidence of Delirium.

PURPOSES: To clarify the incidence and risk factors of postoperative delirium in patients following pancreatic surgery, and the impact of yokukansan (TJ-54) administered to reduce delirium. METHODS: Fifty-nine consecutive patients who underwent pancreatic surgery (2012.4-2013.5) were divided into 2 groups: TJ-54 group: patients who received TJ-54 (n = 21) due to insomnia and the No-TJ-54 group: patients who did not receive TJ-54 (n = 38), and the medical records including the delirium rating scale - Japanese version (DRS-J) were retrospectively reviewed. RESULTS: Postoperative delirium occurred in 2 patients (9.5%) in the TJ-54 group and in 4 (10.5%) patients in the No-TJ-54 group (p = 0.90). The DRS-J on 5 days after surgery was lower in the TJ-54 group than in the No-TJ-54 group (rough p = 0.006), however, without any statistically significant differences with the Bonferroni correction. As for the hospital cost, there was no difference between the TJ-54 and the No-TJ-54 groups (p = 0.78). History of delirium was identified as an independent risk factor of postoperative delirium. CONCLUSION: The patients with preoperative insomnia, who were treated with TJ-54, did not have a higher incidence of postoperative delirium, compared to those without preoperative insomnia. The patients who had a history of delirium have an increased risk of postoperative delirium and should be cared for and treated prophylactically to prevent it.