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The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1-/- allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1-/- allografts showed increased infiltrating Ly6G+ and CD11b+ cells in lamina propria on day 4, whereas the degree of CD4+ or CD8+ T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1-/- allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system.

Introduction Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate posttransplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Methods Between January 2005 and December 2017, 1,270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity-score (PS) matched patients without thrombosis (control group), using a 1:3 matching model. Results The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; p=0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (p=0.133 and p=0.166, respectively). Conclusion RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

Introduction: Postoperative biliary complications in living donor liver transplantation are often difficult to treat, and if treatment is not successful, the patient’s QOL is significantly reduced. The frequency of postoperative biliary complications is reported to be higher than that of deceased donor transplantation. In 2013, Lin et al. reported that while biliary reconstruction has traditionally used a surgical surgical loupe (2.5x–4.5x), biliary reconstruction using a surgical microscope (5x–15x) can reduce the incidence of complications. The objective of this study is to clarify the efficacy of biliary reconstruction using surgical microscope in living donor liver transplantation by a multi-facility, randomized comparative study. Methods and analysis: It is an open-label randomized controlled study in which target patients who meet the registration requirements are randomly allocated to a surgical loupe group and a microscopy group after obtaining their consent (Ratio 1:1). The primary endpoint is an incidence of biliary complications (bile leakage and anastomotic biliary stricture) with Clavien-Dindo class III or higher within 52 weeks following surgery. The secondary endpoint is length of time required for biliary reconstruction using a surgical microscope. Ethics and dissemination: This study protocol was approved by the institutional review board of Nagasaki University Hospital (No. 20122102-2). The study is registered in UMIN-CTR as UMIN000042011. Written informed consent will be obtained from all participants. The results will be published in a peer-reviewed journal and will be presented at medical meetings. Highlights Postoperative biliary complications in living donor liver transplantation are often difficult to treat. Lower incidence of biliary complication following biliary reconstruction using a surgical microscope has been reported. Facilities those use a surgical microscope for biliary reconstruction are limited. The first study to investigate the efficacy of surgical microscope for biliary construction in liver transplantation by randomized controlled trial.

The feasibility of pancreas transplantation (PT) in older recipients remains a matter of debate. We examined the influence of recipient age on PT outcomes and identified the prognostic factors for older recipients. We compared the outcomes of PT in recipients aged

Transjugular intrahepatic portosystemic shunt has been established as an effective treatment for complicated portal hypertension. This retrospective study investigated the effect of pretransplant transjugular intrahepatic portosystemic shunt placement on intraoperative graft hemodynamics and surgical outcomes after liver transplantation.Of 1,081 patients who underwent liver transplantation between January 2007 and June 2017 at Cleveland Clinic (OH, USA), 130 patients had transjugular intrahepatic portosystemic shunt placement before liver transplant. We performed a 1:2 propensity score matching to compare intraoperative graft hemodynamics and surgical outcomes between the transjugular intrahepatic portosystemic shunt group (n = 130) and the no-transjugular intrahepatic portosystemic shunt group (n = 260).The transjugular intrahepatic portosystemic shunt did not increase operative time, the volume of blood transfusion, duration of hospital stay, or complication rates. Graft and patient survivals were similar between the groups. Mean intraoperative cardiac output and graft portal flow in the transjugular intrahepatic portosystemic shunt group were greater than in the no-transjugular intrahepatic portosystemic shunt group (P = .03 and P = .003, respectively). In multivariate analysis, male sex, younger age, low platelet count, absence of portal vein thrombosis, and pretransplant transjugular intrahepatic portosystemic shunt placement were independently associated with increased portal flow volume (Por = 0.03 each). Transjugular intrahepatic portosystemic shunt malposition was observed in 17 patients (13.1%). The 1-year patient survival was 70.6% with transjugular intrahepatic portosystemic shunt malposition and 92.0% without transjugular intrahepatic portosystemic shunt malposition (P = .01).Our findings suggest that pretransplant transjugular intrahepatic portosystemic shunt placement increases graft portal flow but does not compromise surgical outcomes after liver transplantation. Transjugular intrahepatic portosystemic shunt malposition, however, is not uncommon and may increase the complexity of transplantation.

BACKGROUND Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

The Chao Phraya River and the network of canals or “klongs” are the origin of Bangkok’s nick-name “Venice of the East”. Its amphibian nature of lower delta area where used to be covered by the sea around 5000 years ago provides a water-based settlement for the citizens. Rivers as an agricultural irrigation system are also used for daily consumption, transportation, and drainage channels. Bangkok was established in 1782 as the capital of Thailand by King Rama I of the Chakri Dynasty. The location is on a flood plain delta of the Chao Phraya River with the same consideration as the up north old capital Ayutthaya; the river is performed as a natural defense against enemies and also provides a water-based settlement for the citizens. The worst flood in Thailand’s history occurred during the 2011 monsoon season; July to November; that became the severest flood disaster hit parts of the capital city of Bangkok and resulted in a total of 815 deaths and 65 of Thailand’s 77 provinces were declared flood disaster zones, and over 20,000 square kilometers (7700 square miles) of farmland was damaged. The most affected areas were the recent capital Bangkok and the old capital Ayutthaya. The major causes were not only from the natural disaster but also water management failures from the human disaster. The studies aimed to include the survey of after-flood areas, reviewing the history of the waterfront communities and their attitudes toward development and changes, then discussed threats and crisis to the cultural landscape, the cause and effects of the disaster, the theoretical framework of the best management practices and the resolutions models proposed by the involved authorities. Whilst, history also gives us a sense of identity and traditional wisdom, the paper tried to find a paradigm shift and invented best practices for future generation flood protection using “the meaning and spirit of cultural landscape” model.

This study is being performed to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms, and to examine the effects of DKT on small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities. This is a randomized, open, controlled trial using patients treated with usual care as the control group. Patients who meet the inclusion criteria are randomized to the study groups. Eligible patients are randomized to the DKT therapy group (DKT administration for 14 days postoperatively or until the day of discharge if a patient leaves the hospital less than 14 days after the surgery) or the usual care group (no administration of DKT (ratio 1:1). Using the NRS (numeric rating scale) as an indicator, we will attempt to show whether DKT is effective for abdominal pain and bloating after surgery by comparing both groups. We will also attempt to evaluate postoperative small intestinal mucosal atrophy using DAO and GLP-2 activities in the serum, and postoperative nutrient absorption using nutrient assessment indicators. This study is being conducted according to the CONSORT statement. A consent form was signed by all participants, and the study protocol has been approved by the Central Review Board and Local Ethics Committee (CRB7180001).

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] mg/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.

We report on the case of a 50-year-old female patient with symptomatic polycystic liver disease who underwent living donor liver transplantation (LDLT) using right liver graft from her ABO-identical husband. To achieve operational tolerance, regulatory T-cell (T-reg)-based cell therapy was applied, following the protocol introduced by Todo et al. Briefly, donor lymphocytes were collected by leukapheresis 20 days before LDLT without any adverse events, and the cells were irradiated with a dose of 30 Gy and kept frozen. Lymphopheresis of the recipient was conducted in a similar manner 1 day before LDLT, and donor cells and recipient cells were cultured with anti-CD80/86 antibodies to induce the donor-specific T-reg. At 14 days of culture, the CD4+CD25+Foxp3+ cells had increased from 1.51% to 5.21%, and mixed lymphocyte reaction assay using an intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester-labeling technique revealed donor-specific hyporesponsiveness of CD4-positive lymphocytes. On postoperative day (POD) 13 (14 days of culture), these cells were infused to the recipient intravenously without any adverse events. Initial immunosuppression consisted of tacrolimus, steroid and mycophenolate mofetil (MMF), and cyclophosphamide (40 mg/kg) administered on POD 5. Both the steroid and MMF were continued until 4 weeks after LDLT, and the patient was discharged on POD 30 with normal liver function. On POD 52, the patient developed acute cellular rejection and received appropriate reinforcement of immunosuppressive therapy and is currently doing well with normal liver function 30 months after LDLT with reduced anti-donor allo-activity. In summary, T-reg therapy was safely performed in adult LDLT, and we are following the patient carefully to determine whether she can achieve operational tolerance in the future.

The aim of this study was to analyze changes in characteristics of HCC and the modes of LR over 20 years in order to show the impact of those changes in the outcome of LR. In addition, BCLC staging was used to assess the limitations of this classification system and changes over the decade. In our department, 500 liver resections (LR) were performed for hepatocellular carcinoma (HCC) over the 20 years between January 2000 and February 2020. The 208 cases performed through 2009 were designated as Era 1, and the 292 cases between 2010 and February 2020 were termed Era 2. We analyzed changes in the characteristics of HCC and mode of LR (Study 1), and final outcomes of LR are shown according to the BCLC staging classifications and eras using data from the 5 years after LR (Study 2). In Era 1, the mean age of the patients was 68, while in Era 2 the mean age was 71, which was significantly older than the patients in Era 1. HCC that developed from non-B, non-C liver cirrhosis was significantly increased in Era 2 (45%) as compared to that in Era 1 (34%). Laboratory data were all comparable between the eras in patients undergoing LR for HCC. The size and numbers of the HCC as well as tumor markers were similar between the eras. As to the mode of LR, although the extent of LR was similar between the eras, the laparoscopic method was significantly increased in Era 2. Blood loss was significantly lower in Era 2 (mean 519 g) than in Era 1 (1,085 g). Patient survival and recurrence-free survival (RFS) were similar between the two eras, while RFS at 5 years after LR was better in Era 2. Even in the BCLC A category, only patients with a single HCC less than 5 cm showed best results, while patients with HCC within the rest of BCLC A and BCLC B showed a dismal outcome. There was no difference in OS and RFS between the eras after stratification by BCLC. There are conspicuous changes in the baseline characteristics and mode of LR over 20 years, which should be taken into account for patient care and informed consent for patients undergoing LR going forward.

Background: The impact of pancreas transplantation, including kidney transplantation on patients&rsquo, life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. Methods: The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. Results: The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. Conclusion: Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.

Although experimental studies have reported that hepatic ischemia-reperfusion injury promotes tumor growth and metastases, the impact of graft hemodynamics on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is unclear. To investigate the association between graft hemodynamics and HCC recurrence after LT, we conducted a retrospective analysis of 279 patients who underwent LT for HCC. Graft hemodynamics including portal vein flow (PVF), hepatic artery flow (HAF), and total hepatic flow (THF) was analyzed as a predictor of HCC recurrence, using competing risk regression analyses. The cutoff values of PVF, HAF, and THF were set at the lower quartile of distribution. A cumulative recurrence curve demonstrated that low THF (

Backgrounds: Prior studies have suggested that drain amylase level is a predictive marker for developing pancreatic fistulas (PFs) after pancreaticoduodenectomy (PD). However, means of preventing PF after discovering high drain amylase levels have not been previously established. The purpose of this study was to evaluate the efficacy of a combination drug therapy (using three drugs; gabexate mesilate, octreotide, and carbapenem antibiotics, named as triple-drug therapy [TDT]) regimen in preventing PF for patients with high drain amylase levels on postoperative day (POD) 1 after PD. Materials and methods: We divided the 183 patients who underwent PD into two groups in accordance with their enrollment in the study: for those enrolled early in the study (early period), TDT was not administered to patients with high drain amylase level; however, for those enrolled later in the study (late period), TDT was administered if drain amylase levels were over 10,000 IU/L on POD 1. We retrospectively compared the incidence of PF between the two groups. Results: Incidences of PFs were statistically, significantly prevented in the late group (early 17% versus late 6%; P = 0.01). For patients with low levels of drain amylase (, Journal of Surgical Research, 234, pp.77-83; 2019

Some patients experience very late recurrence of HCC more than 5 years after initial therapy. We aimed to clarify the predictive factors for very late recurrence of HCC in such cases. Among 807 HCC patients undergoing surgical resection or ablative therapy with curative intent, the patients who survived for 5 years without any recurrence were reviewed. The prognosis and possible predictive factors for late recurrence were analyzed retrospectively. A total of 184 patients survived for more than 5 years without recurrence. Among them, 61 patients experienced recurrence, at a median of 6 years after initial therapy. In univariate analysis, the pre-treatment aspartate aminotransferase, alanine aminotransferase, Child-Pugh class, and ALBI grade were not related to recurrence, but those at 5 years after treatment were significantly related to recurrence. By multivariate analysis, an ALBI grade of 2–3 at 5 years was an independent risk factor for recurrence (P

The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child–Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P

Islet transplantation is a feasible treatment option for type 1 diabetes mellitus (T1DM) patients with a poor glycemic control. However, while the outcomes of islet transplantation have recently improved, early graft loss after transplantation remains a problem. Several factors are associated with islet graft loss in intrahepatic islet transplantation, including instant blood-mediated inflammatory reaction, hypoxia and liver immunity, and procedure-related complications, such as portal vein thrombosis and hemorrhaging. To overcome these problems, many researchers have attempted to change the transplantation site from the portal vein to the subcutaneous space using tissue-engineered sheets. However, the subcutaneous space is easy to access, and the procedure itself is minimally invasive, although the efficiency has been lower than that with transplantation via portal vein in previous studies due to the hypoxic environment. Therefore, subcutaneous islet transplantation using tissue engineering has attracted attention in recent years. In this report, we discuss the concept of subcutaneous islet transplantation using tissue engineering.

Objective Portal vein thrombosis (PVT) does not preclude liver transplantation (LT), but poor portal vein (PV) flow after LT remains a predictor of poor outcomes. Given the physiologic tendency of the hepatic artery (HA) to compensate for low PV flow via vasodilation, we investigated whether adequate HA flow would have a favorable prognostic impact among patients with low PV flow following LT. Methods This study included 163 patients with PVT who underwent LT between 2004 and 2015. PV and HA flow were categorized into quartiles, and their association with 1-year graft survival (GS) and biliary complication rates was assessed. For both the HA and the PV, patients at the lowest two quartiles were categorized as having low flow and the remainder as having high flow. Results The median MELD score was 22 and 1-year GS was 87.3%. As expected, GS paralleled PV flow with patients at the lowest flow quartile faring the worst. In combination of PV and HA flows, high HA flow was associated with improved 1-year GS among patients with low PV flow (P = .03). Similar findings were observed with respect to biliary complication rates. Conclusions Sufficient HA flow may compensate for poor PV flow. Consequently, meticulous HA reconstruction may be central to achieving optimal outcomes in PVT cases.

BACKGROUND While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT. METHODS We retrospectively investigated 1001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into 3 groups according to hazard ratio for 1-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups. RESULTS The low-PF group (PF < 65 mL/min/100 g, n = 210, P = 0.011) and the high-PF group (PF ≥ 155 mL/min/100 g, n = 159, P = 0.018) showed significantly poorer 1-year graft survival compared with the intermediate-PF group (PF ≥ 65 mL/min/100 g and < 155 mL/min/100 g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups. CONCLUSIONS These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT.

One-stage curative surgical resection for obstructive colon cancer is challenging. Self-expandable metallic stents (SEMSs) are known as an alternative treatment used to avoid emergency operation. We aimed to evaluate the significance of SEMS placement as a bridge to surgery and the surgical outcomes of the elective operation. A consecutive 20 patients with obstructive colon cancer undergoing SEMS placement between June 2014 and February 2016 were included. The technical outcomes of the SEMS placement, surgical procedures, and surgical outcomes were evaluated retrospectively. Among them, 2 patients were treated with a SEMS palliatively, and the others were treated with a SEMS as a bridge to surgery. All SEMS were placed successfully at the first attempt, and there was no SEMS-related complication. Before surgery, all patients could be diagnosed histologically, and they were evaluated systemically including proximal colon or distant metastasis. The median time to operation after SEMS placement was 14 days (range 9–20 days). Seven of the 18 patients underwent a laparoscopic colectomy without conversion to laparotomy. All patients with stage II or III colon cancer underwent curative surgery, and 2 patients with stage IV colon cancer underwent a one-stage resection of the primary colon cancer and simultaneous liver metastasis after the evaluation of hepatic functional reserve. There was no mortality or SEMS-related complication in the perioperative period. SEMS placement as a bridge to surgery for patients with obstructive colon cancer is safe and effective to provide an adequate amount of time for a preoperative systemic management and evaluation.

The hepatic venous pressure gradient (HVPG) measurement is known to correlate with the severity of portal hypertension in patients with liver cirrhosis. This retrospective study investigated the clinical value of preoperative measurement of HVPG in patients who underwent adult-to-adult living donor liver transplantation (LDLT) and its predictive value for hepatic hemodynamics after graft reperfusion. For this study, 75 patients who underwent adult-to-adult LDLT were divided into 2 groups (HVPG

Background Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. Aims To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. Methods Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. Results Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration ( P = 0.034) and poor overall survival ( P = 0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines. Conclusions Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition.

Background: Pancreatic ductal adenocarcinoma (PDAC) is known as one of the most malignant potential diseases with poor neovascularization. By comparing PDAC to hepatocellular carcinoma (HCC), which is well vascularized, we investigated the mechanisms and tumor biological significance of the poor neovascularization in PDAC. Methods: Surgical specimens from primary PDAC and HCC patients were immunohistologically stained to detect the expressions of CD105, CD44, HIF-1α, PHD3, and Siah2. We also used two PDAC and two HCC cell lines to compare the expressions of HIF-1α, PHD3, and CD44, as well as the production of VEGF in hypoxic condition. The role of PHD3 in regulating HIF-1α expression was further confirmed by siRNA knockdown in a PDAC cell line that highly expressed PHD3. Results: There were significantly fewer microvessels but more cancer stem cells in PDAC specimens compared to HCC specimens. The expression of CD105 was reversely related to the expression of CD44 in PDAC and HCC specimens. PDAC specimens also showed higher expressions of PHD3 but lower expressions of HIF-1α. Similarly, the expression of PHD3 was observed clearly in PDAC cell lines, but was almost completely negative in HCC cell lines. Hypoxic stimulation clearly enhanced HIF-1α expression and VEGF secretion in both HCC cell lines, but did not significantly change in PDAC cell lines. The knockdown of PHD3 in PDAC cells restored the hypoxic-induced HIF-1α expression, which accordingly stimulated the cells’ VEGF secretion. Conclusions: The enhanced expression of PHD3 might likely contribute to the poor neovascularization and affect the biological characterization in PDAC cancer cells., Journal of Gastroenterology, 50(9), pp.975-983; 2015

The effects of achieving sustained virological response (SVR) on recurrence and survival after curative treatment in patients with hepatitis virus C (HCV)-related hepatocellular carcinoma (HCC) is unclear. This study examined the influence of SVR achievement by interferon therapy before HCC occurrence on recurrence and survival. This retrospective study included 518 patients who underwent surgical microwave ablation for initial HCV-related HCC between January 2001 and December 2015. Thirty-four patients had achieved SVR (SVR group) and 484 patients had not (control group). Clinical characteristics and long-term outcomes were compared between the two groups. Overall survival rates at 5 and 10 years after curative ablation were 95.8 and 80.4% in the SVR group, and 50.7 and 23.4% in the control, respectively (p

Summary: Background: Indications and efficacy of surgical treatment for liver metastases from gastric cancer (LMGCs) remain controversial. This retrospective study was designed to clarify the benefits of surgical treatment and identify prognostic factors. Methods: Between December 1997 and December 2015, 34 consecutive patients underwent hepatic resection and surgical microwave ablation for synchronous or metachronous LMGCs at our institution. We analyzed their cumulative overall survival (OS) and recurrence-free survival (RFS) rates and clinical parameters to identify predictors of prognosis. Results: Of the 34 patients, 14 underwent hepatic resection, 13 underwent surgical microwave ablation, and 7 underwent hepatic resection combined with surgical microwave ablation. Their OS rates were 1-year: 84.4%, 3-year: 38.6%, and 5-year: 34.7%; and their RFS rates were 1-year: 38.5%, 3-year: 28.0%, and 5-year: 28.0%. OS did not significantly vary among the surgical procedures. In multivariable analysis, positive of both CEA and CA19-9 were independent predictors of poor survival (hazard ratio [HR] 4.51; P = 0.049) and early recurrence (HR 5.70; P = 0.047). Conclusions: Both hepatic resection and surgical microwave ablation for LMGCs are effective and can improve survival in selected patients. Keywords: Gastric cancer, Liver metastasis, Hepatectomy, Liver resection, Microwave ablation

Background/objectives: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) for low-grade malignant pancreas tumors was recently demonstrated. Although the procedure with splenic vessel preservation (SVP) is optimal for LSPDP, SVP is not always possible in patients with a large tumor or a tumor attached to splenic vessels. This study aimed to analyze the safety of two procedures: LSPDP without SVP, known as the Warshaw technique (lap-WT), and LSPDP with SVP (lap-SVP). Methods: Seventeen patients who underwent a lap-WT and seven patients who underwent a lap-SVP were investigated retrospectively. Results: The median follow-up duration was 45 (range 17-105) months. In the lap-WT and lap-SVP patients, the sizes of the tumors were 5 (1.3-12) and 1.5 (1-4) cm; the operative times were 304 (168-512) and 319 (238-387) min; the blood loss was 210 (5-3250) and 60 (9-210) gr; the length of the postoperative hospital stay was 15 (8-29) and 18 (5-24) days; the peak platelet counts were 37.2 (14.6 -65.2) and 26.4 (18.8-41) × 104/μL, and splenomegaly was observed in 10 (59%) and three (43%) patients, respectively. In both procedures, there was no local recurrence. In the lap-WT group, splenic infarctions were seen in four (24%) patients and perigastric varices were seen in two (12%) patients. All of these patients were observed conservatively. Conclusions: Both the lap-WT and lap-SVP were found to be safe and effective, and in cases in which the tumor is relatively large or close to the splenic vessels, lap-WT can be used as the more appropriate procedure., Pancreatology, 14(6), pp.530-535; 2014

Background: Internal pancreatic fistula (IPF) is a well-recognized complication of pancreatic diseases. Although there have been many reports concerning IPF, the therapy for IPF still remains controversial. We herein report our experiences with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its validity. Method: Six patients with IPF who presented at our department and received endoscopic transpapillary pancreatic stent therapy were investigated, focusing on the clinical and imaging features as well as treatment strategies, the response to therapy and the outcome. Results: All patients were complicated with stenosis or obstruction of the main pancreatic duct, and in these cases the pancreatic ductal disruption developed distal to the areas of pancreatic stricture. The sites of pancreatic ductal disruption were the pancreatic body in five patients and the pancreatic tail in one patient. All patients received endoscopic stent placement over the stenosis site of the pancreatic duct. Three patients improved completely and one patient improved temporarily. Finally, three patients underwent surgical treatment for IPF. All patients have maintained a good course without a recurrence of IPF. Conclusion: Endoscopic transpapillary pancreatic stent therapy may be an appropriate first-line treatment to be considered before surgical treatment. The point of stenting for IPF is to place a stent over the stenosis site of the pancreatic duct to reduce the pancreatic ductal pressure and the pseudocyst's pressure., Pancreatology, 13(6), pp.621-624; 2013

With increased economic and tourism interests in both Japan and Russia, culturally different meanings of ‘forest’ need to be understood for future cooperative environmental management. In this study, we propose Landscape Image Sketching Technique as an original, practical methodology to externalise an individual landscape image as a scene sketch aiming to represent the viewer's fundamental way of seeing the landscape. To discuss different perceptions and interpretations of forests in a cultural framework, we conducted cross-national research in Japan and Russia. A total of 325 respondents were asked to make a landscape image sketch of an imaginary forest and to include keywords and text. The sketches were analysed by means of four aspects: ‘linguistic knowledge’, ‘spatial view’, ‘self-orientation’ and ‘social meaning', which were represented by landscape elements, the shape of elements, the subject's standpoint and the combination of the elements in the framework. As a result, landscape image sketches revealed differences between respondents in Japan and Russia. The typical landscape images of a forest were represented objectively, as aesthetic scenery in Russia and subjectively, as a practical place in Japan. The results suggested a fundamental difference in ways of seeing the landscape through individual perceptions rather than normative views on forests. This methodology for visualising ways of seeing a landscape can be useful in understanding different assumptions about environmental issues, not only for a global environmental discussion regarding each locality, but also for local environmental management and public participation.

In this study were compared three different management type sandy coast , and considered as subjects for appropriate recreational use management on Ishikari coast, Hokkaido. 1,000 questionnaire surveys were distributed on the site and 375 were returned back by mail. The purposes of the visitors, and also their attributes, were different in regard to the management type of the coast. The park users were elder and were interested in conservation of coastal plants. Although the beach users should have paid for parking lots, they had complained about insufficient facilities and their maintenance. The non-managed beach users had various purposes, like swimming, camping, fishing, ATV and PWC riding, but such purposes had caused conflict between users, and had significantly higher points of awareness of the issues such as leaving garbage, human waste, and annoyed other visitors. As a result of this research it may be concluded that strict rules and regulations are needed for non-managed beaches for sustainable recreational use. It can also be suggested that the collection of entrance fees or parking charge at non-managed beaches will work effectively towards user management. Coastal managers should develop sustainable management strategy and preserve the coasts for the future generations.

Ishikari coast, Hokkaido, has valuable natural beaches, dunes, forest and other natural resources. But in the last few decades, serious environmental problems and conflicts among recreational users have occurred because of heavy recreational use of the coastal areas. However, neither new regulations nor management systems have been established in this area yet. The purpose of this study is to point out the effectiveness of the interpretation method (informing visitors) in help of establishing a system to better manage users’ behaviors. Questionnaire sheets were distributed to 72 Ishikari coast visitors to survey their opinions on the recreational use problems and on ideas about the optimum management of the Ishikari coast in the future. The results showed that the opinions were different between visitors who were informed about the environmental problems of Ishikari coast (interpreted groups) and those were not (non-interpreted groups). The interpreted groups were likely to prefer more conservancy oriented management and environmentally friendly use of coastal natural resources than non-interpreted groups. This result indicates that informing visitors about the environmental problems with the help of an interpreter can be an effective tool for the management of public beach resorts.

Background: Early postoperative pain after transabdominal preperitoneal hernia repair (TAPP) has been frequently reported. However, the incidence and degree of chronic pain after TAPP have not been evaluated. Therefore, author aimed to examine chronic pain after TAPP.Methods: A total of 256 who underwent TAPP between November 2008 and March 2015 at the institute were enrolled. Original questionnaires focusing on the current state of pain were sent to the enrolled patients by mail. The incidence, body location, and degree of chronic pain occurring at least 6 months after the initial surgery were evaluated. In addition, a medical chart review of patients with and without chronic pain was performed to determine the predictive factors of chronic pain.Results: The survey response rate was 43.8% (112/256). The median follow-up period after the initial surgery was 44.3 months (range, 9.7-80.3 months). Sixty percent of patients experienced pain after TAPP; however, in 56.2% of the patients, the pain had mitigated 1 week after TAPP. Ten percent (12/112) of the patients had chronic pain 6 months after TAPP. Pain in the inguinal region was more frequently reported than any other wound region (67% vs 25%, p =0.0009). Although most of the patients with pain felt the pain occasionally, three of twelve patients (25%) complained of daily pain and had high VAS score. No significant predictive factors of chronic pain were identified.Conclusions: Ten percent of patients experienced chronic pain after TAPP. Large scale prospective trials are needed to identify the predictive factors of chronic pain.

Objective Prior studies suggested that early drain removal prevented the development of pancreatic fistula (PF) after pancreaticoduodenectomy (PD), but there has been no corresponding prospective trial for distal pancreatectomy (DP). The purpose of this study was to determine the safety and efficacy of early drain removal and triple-drug therapy (TDT) with gabexate mesilate, octreotide and carbapenem antibiotics to prevent PF after DP in patients at high-risk of developing PF. Methods A total 71 patients who underwent a DP were enrolled. We prospectively divided them into two groups: the late-removal group, in which the drain remained in place for at least for 5 days postoperatively (n = 30) and the early-removal group in which the drain was removed on postoperative day 1 (POD1) (n = 41). For the patients with a high drain amylase level (?10,000 IU/L) and patients with symptomatic intraperitoneal fluid collection, our original TDT was introduced. The primary endpoint was the safety and efficacy of this management, and the secondary endpoint was the incidence of PF. Results The incidence of clinical PF was significantly lower in the early-removal group (0% vs. The late removal 16%; p < 0.001). In the early-removal group, TDT was administered to 12 patients (29%) and none of the patients needed additional treatment after TDT. Conclusions Postoperative management after DP with early drain removal and TDT was safe and effective for preventing PF., Pancreatology, 15(4), pp.411-416; 2015

医療関係機関などから発生する特別管理廃棄物には, 病原微生物によって感染症を生じる恐れのある感染性廃棄物のほか, 毒性の強い化学物質を含有する有害性廃棄物が存在することもある。本稿では医療研究機関および附属病院から発生する廃棄物のうち, 主として特別管理廃棄物を取り上げて, 医療関係機関などの責務, 医療廃棄物への対応, その課題と対策について解説する。浜松医科大学医学部および附属病院における廃棄物処理については, 特別管理廃棄物である非感染性廃棄物の廃油, 廃酸または廃アルカリをそれぞれ排出時点でプラスチック製専用容器に分別した後, 施設内で廃油を噴霧燃焼法で焼却処理し, 廃酸または廃アルカリはフェライト化法で処理している。感染性廃棄物については施設内外での感染事故を防止するため, 液状またはでい状のもの, 固形状のもの, 鋭利なものに厳格に分別して専用保管場所に貯留し, 委託処理にて焼却処理されている。医療廃棄物に対する課題と対策では, 鋭利なものによる感染事故の防止, 発がん性廃棄物, 抗悪性腫瘍剤廃棄物, DNA廃棄物などについて述べた。

Prolonged hyperbilirubinemia (HB) following living donor liver transplantation (LDLT) can be a risk factor for early graft loss and mortality. However, some recipients who present with postoperative hyperbilirubinemia do recover and maintain a good liver function.The purpose of this study was to investigate the risk factors for hyperbilirubinemia following LDLT and to identify predictors of the outcomes in patients with post-transplant hyperbilirubinemia.A total of 107 consecutive adults who underwent LDLT in Nagasaki University Hospital were investigated retrospectively. The patients were divided into two groups according to postoperative peak serum bilirubin level (HB group: ≥ 30 mg/dl; non-HB group:30 mg/dl). These two groups of patients and the prognosis of patients in the HB group were analyzed using several parameters.Seventeen patients (15.9 %) presented with hyperbilirubinemia, and their overall survival was significantly worse than patients in the non-HB group (n = 90). Donor age was significantly higher in the HB group (P0.05). Of the 17 patients in the HB group, nine survived. The postoperative serum prothrombin level at the time when the serum bilirubin level was30 mg/dl was significantly higher in surviving patients (P0.01).The use of a partial liver graft from an aged donor is a significant risk factor for severe hyperbilirubinemia and a poorer outcome. However, those patients who maintain their liver synthetic function while suffering from hyperbilirubinemia may recover from hyperbilirubinemia and eventually achieve good liver function, thus resulting in a favorable survival.

Title Laparoscopic Middle Pancreatectomy under a Pancreatic Duct-Navigation Surgery Author(s) Kitasato, Amane; Adachi, Tomohiko; Inokuma, Takamitsu; Tajima, Yoshitsugu; Kanematsu, Takashi; Kuroki, Tamotsu Citation Hepato-Gastroenterology, 59(120), pp.2400-2402; 2012 Issue Date 2012-11 URL http://hdl.handle.net/10069/31336 Right © H.G.E. Update Medical Publishing S.A. NAOSITE: Nagasaki University's Academic Output SITE

s / Pancreatology 14 (2014) S1eS129 S113 min (168-512)/316 min (238-376), 443 gr (5-3250)/96 gr (9-210), and 16 days (8-29)/16 days (5-24), respectively. There was no grade B or C pancreatic fistula in both procedures. The postoperative maximum platelet counts in WT/SVP were 36.3/10.9 104/ml. Five patients (28%) with splenic partial infarction and 2 patients (11%) with gastric varices in WT were observed without any treatments. In SVP, There were no complications in the splenic circulation. No local recurrences were seen in both procedures. Conclusion: Two procedures of LSPDP for benign and low-grade malignant tumors are safe and effective.