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The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined.To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC.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.Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells10% (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 CRT83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR.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.

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.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.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.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.

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 naive 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.

In this paper, we report a novel technique that enabled us to easily and effectively conduct an accelerated degradation test on a small pressure vessel for potable and hot water pipes. Accelerated degradation tests were carried out on polybutene (PB) pipes with and without pressurization, under chlorinated and non-chlorinated water at 80 °C; the higher-order structure changes, residual antioxidant agents, and degradation characteristics of the PB pipes were evaluated. In the degradation test under chlorine water, the isothermal oxidation induction time (I-OIT) time and the mechanical properties decreased with increasing aging time. Additionally, micro- Fourier transform infrared spectroscopy (FT-IR) imaging revealed the distribution of antioxidants in the PB pipe before and after the test, while in the degradation test under pressure, the residual amount of antioxidants was smaller, and the chemiluminescence intensity was higher compared with the test that was not pressurized. These results strongly suggest that not only dissolved chlorine but also water pressure contribute to promoting the degradation of plastic pipes, and that the simple pressure vessels allow the safe and easy testing of accelerated degradation.

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).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.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 CRT0.6 were significantly higher than those in 45 patients0.6: 65% and 60% vs. 24% and 20% (p = 0.0001). The patients with PV patency ratio0.6, 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.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.

Background Biliary complication is one of the major donor complications during and after hepatectomy in living donor liver transplantation (LDLT). We evaluated risk factors for donor biliary complication in adult-to-adult LDLT. Patients and Methods From March 2002 to November 2016, 126 consecutive patients who underwent donor hepatectomy in adult-to-adult LDLT were divided into 2 groups according to biliary compilations: nonbiliary complication (non-BC) group (n = 114) and biliary complication (BC) group (n = 12). Results Among 126 donor hepatectomies, 35 patients (28%) experienced perioperative complications, including 10 (7.9%) with Clavien-Dindo classification grade III. Biliary complications occurred in 12 patients (9.5%): bile leakage in 10 and intraoperative bile duct injury in 2. Additional computed tomography- and/or ultrasound-guided drainage or exchange of original drain was required in 7 patients. In comparison between BC and non-BC groups, future remnant liver volume was significantly higher in the BC group than in the non-BC group (63% vs 40%; P = .02). In multivariate analysis, larger future remnant liver volume (P = .005) and shorter operating time (P = .02) were identified as independent risk factors for biliary complications. We had 2 patients with intraoperative bile duct injury: both were successfully treated by duct-to-duct biliary anastomosis with insertion of biliary stent or T-tube. Conclusion Large remnant liver volume was a significant risk factor for biliary complications, especially biliary leakage, after donor hepatectomy. For intraoperative bile duct injury, duct-to-duct anastomosis with biliary stent is a feasible method to recover.

Background Portal vein (PV) reconstruction is a crucial factor in successful living donor liver transplantation (LDLT). In LDLT using the right liver grafts with anatomic PV variations, we sometimes encounter dual PV anastomosis. In this study we describe PV variations of donor liver in detail as well as our experiences with PV reconstruction in right liver grafts with PV variations. Methods We performed LDLT in 149 recipients between 2002 and 2016. PV variations of donor liver were classified into 3 major anatomic patterns, and we retrospectively analyzed the procedure and postoperative complications of PV anastomosis. Results PV variations in donor livers were classified as type A (normal type) in 125 patients, type B (trifurcation type) in 7 (4.7%), and type C (caudal origin of the right posterior branch) in 17 (11.4%). Among 75 right liver grafts, 10 (13.3%) had anatomic PV variations. In 9 of 10 recipients, dual PV of the graft were anastomosed to dual PV branches of the recipient in direct end-to-end fashion. In the remaining recipient, the posterior portal branch of the graft was anastomosed to the recipient portal trunk through the interposed venous graft in end-to-end fashion and the anterior portal branch of the graft was anastomosed to the side wall of the interposed venous graft. These 10 recipients did not develop any postoperative complications associated with PV anastomosis, although 3 of the 149 recipients (2.0%) developed complications associated with PV anastomosis, such as thrombosis and necrosis. Conclusion Dual PV anastomosis of the right liver graft is safe and feasible in LDLT, even in anatomic PV variations.

In an attempt to increase the number of donor livers, there has been an increased use of marginal donor livers, such as steatotic (fatty) livers that increase susceptibility to ischemia and reperfusion injury (IRI). Inflammatory cell accumulation has a greater role in IRI in steatotic liver than in normal liver. Although the recombinant human soluble thrombomodulin (rhsTM) attracts attention as a new treatment for disseminated intravascular coagulation, the therapeutic efficacy of rhsTM in hepatic IRI remains uncertain, especially in fatty livers. We aimed to demonstrate the effect of rhsTM on hepatic IRI using well-established in vivo experimental models with steatotic liver. Methods C57/BL6 mice were divided into 2 groups: normal liver (NL) group and fatty liver (FL) group, in which the steatotic liver was induced by high-fat diet for 9 weeks. The mice in the NL and FL groups were premedicated with venous injection of rhsTM (TM) or saline (Control) as control groups. All 4 groups (NL-Control vs NL-TM, FL-Control vs FL-TM) were subjected to partial hepatic warm ischemia followed by reperfusion. Results rhsTM significantly attenuated liver injury in the FL group as well as the NL group, as evidenced by transaminase levels and histologic finding after hepatic IRI. rhsTM remarkably decreased the accumulation of inflammatory cells, such as macrophages and neutrophils, in both NL and FL tissue after IRI. Furthermore, rhsTM depressed mRNA and protein expressions of adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both NL and FL groups after IRI. Conclusion Our results demonstrate that rhsTM has a protective effect on fatty liver as well as normal liver after hepatic IRI. They also suggest that rhsTM contributes to attenuation of leukocyte accumulation caused by depressing expressions of adhesion molecules that facilitate accumulation of leukocytes in liver tissue in hepatic IRI.

Objective In patients with living donor liver transplantation (LDLT), late-onset complications sometimes develop because of long-term use of immunosuppressive drugs. One of the immunosuppressive drug-related complications is de novo malignancies resulting in reduced survival. Patients and Methods Among 153 patients undergoing LDLT, we retrospectively reviewed the medical records of 97 adult recipients (February 2002 to May 2017), who had been followed-up at our hospital for more than one year after LDLT. The median age was 52 years old (20–70) and the median observational period was 6.9 years (2.4–15.3). Results De novo malignancy after adult LDLT developed in 11.3% (11/97) of patients, including posttransplantation lymphoproliferative disorder (PTLD) (n = 4) (2 in the brain and 2 in abdominal lymph nodes), lung cancer (n = 1), pancreatic cancer (n = 1), gastric cancer (n = 1), laryngeal cancer (n = 1), lower gingival cancer (n = 1), bladder cancer (n = 1), and melanoma (n = 1). Age at cancer diagnosis ranged from 36 to 70 years old with an average age of 61 years. The interval from LDLT to cancer diagnosis was 8.3 years (3.9–12.2). Four patients (36.6%) including PTLD (n = 2), lung cancer (n = 1), and pancreatic cancer (n = 1) died of cancer and all of them were diagnosed with cancer within 10 years after LDLT. Six patients were diagnosed with cancer more than 10 years after LDLT and all of them survived after treatment of cancer. Conclusion De novo malignancy was found in 11.3% of LDLT patients, and more than half of this population subset developed tumors 10 years after LDLT. Long-term close follow-up should be performed by taking any kinds of de novo malignancy into consideration.

A simple and accurate evaluation of the degradation of polymeric products, which are indispensable parts of our daily life, is important for the safe and long-term use of these products. Herein, we present a novel evaluation method for the pipes of polyethylene of raised temperature (PE-RT), a non-cross-linked polyethylene. In this method, we conducted accelerated degradation tests using a custom-designed small pressure vessel. Although it is known that residual chlorine in tap water accelerates the degradation of plastic pipes, this method reveals that the water pressure further accelerates the degradation of the pipes. We demonstrate for the first time that the results of three-dimensional fluorescence spectral studies exhibit a similar trend as those of the conventional isothermal oxidation induction time (I-OIT) measurement. This fluorescence-based method can contribute to the development of new evaluation methods to study plastic degradation, because it is very simple, does not require sample pretreatment, unlike I-OIT and other degradation evaluation methods, and the measurement can be performed directly within a few minutes.

Background & aimsHepatic ischemia-reperfusion injury (IRI), characterized by exogenous antigen-independent local inflammation and hepatocellular death, represents a risk factor for acute and chronic rejection in liver transplantation. We aimed to investigate the molecular communication involved in the mechanism of liver IRI.MethodsWe analyzed human liver transplants, primary murine macrophage cell cultures and IR-stressed livers in myeloid-specific heme oxygenase-1 (HO-1) gene mutant mice, for anti-inflammatory and cytoprotective functions of macrophage-specific HO-1/SIRT1 (sirtuin 1)/p53 (tumor suppressor protein) signaling.ResultsDecreased HO-1 expression in human post-reperfusion liver transplant biopsies correlated with a deterioration in hepatocellular function (serum ALT; p