Search

Aim The formation of a secondary liver is expected in ectopic transplants in liver therapy. It is reported that the transplantation of hepatocyte sheets constitutes one of the techniques used to form a secondary liver. Accordingly, we established a subcutaneous transplant for hepatocyte/fibroblast sheets in previous studies. In this development study with hepatocyte/fibroblast sheets, we evaluated the differences in transplantation sites to promote the maturation of transplanted tissue in a liver injury model. Methods A cocultured hepatocyte sheet of fibroblasts (TIG-118 cells) and human hepatocytes (PXB cells) was prepared on a temperature-responsive culture dish. The prepared cocultured hepatocyte sheet was either transplanted subcutaneously or on the liver surface of a persistent liver injury model (cDNA-uPA/SCID mouse: uPA mouse), and was evaluated by the human albumin concentration in mouse blood. As a control group, hepatocyte cell sheets were used that were transplanted to both areas and compared. Results Although the cocultured hepatocyte sheet led to functional improvements in the early stages of culture in subcutaneous transplantation, these did not last in the long-term after transplantation. Although coculture effects were not observed in the liver surface transplantation case, long-term functional expressions in mono- and cocultured sheets in the case of liver surface transplantation were exhibited compared with subcutaneous administration. Conclusion These results suggest that sustained stimulation of liver regenerationvaries depending on the transplant site and is largely involved in the maturation of hepatocyte tissue.

Introduction Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. Methods Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. Results Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. Conclusions Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs., Highlights • The adipose-derived mesenchymal stem cell sheet is useful to protect the islets. • Subcutaneous islet transplantation on sheet normalized blood glucose in diabetic pig. • Subcutaneous islet transplantation on sheet can be a useful tool.

BACKGROUND Pancreaticobiliary malignant diseases are primarily treated by surgical resection. However, the surgical indications for elderly patients, especially for pancreaticoduodenectomy (PD), must be carefully considered due to patient compliance. Whether PD can contribute to better prognoses in elderly patients remains unclear. Therefore, we aimed to evaluate the complications, compliance, and survival of elderly and non-elderly patients who underwent PD in our department. METHODS We retrospectively analyzed 282 patients who underwent PD from 2000 to 2017 and divided them into non-elderly (aged ≤ 79 years, n = 238) and elderly (aged ≥ 80 years, n = 44) groups. The estimation of physiologic ability and surgical stress (E-PASS) system was used to evaluate morbidity and mortality using preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS). RESULTS Preoperative risk score was higher in the elderly group than in the non-elderly group, although SSS and CRS were similar. No significant differences were detected in the occurrence of postoperative complications. In the elderly group, CRS was higher in patients with complications than in those without. Long-term outcomes evaluated by overall and disease-specific survival were not significantly different. CONCLUSIONS In the elderly patients, E-PASS especially CRS can predict the occurrence of complications. The safety and prognoses of elderly patients after PD are comparable with those of non-elderly patients.

Background/aim We evaluated the safety, feasibility, and preliminary efficacy of Wilms tumor gene 1 (WT1) peptide and Mucin 1 (MUC1)-pulsed dendritic cell (DC) (WT1/MUC1-DC) vaccination as an adjuvant immunotherapy for surgically resectable pancreatic ductal adenocarcinoma (PDA) patients. Patients and methods Eligible patients were administered WT1/MUC1-DC vaccination at least seven times every 2 weeks with concomitant adjuvant chemotherapy after surgical resection of PDA. Results Ten patients were enrolled and no Grade 2 or higher toxicities were associated with DC vaccination. The estimated overall survival (OS) and relapse-free survival (RFS) at 3-years from the time of surgical resection were 77.8% and 35.0%, respectively. Immunohistochemical analysis suggested a possible relationship between induction of WT1-specific cytotoxic T lymphocyte after DC vaccination and higher infiltration of CD3/CD4/CD8 lymphocytes in tumor tissues. Conclusion WT1/MUC1-DC vaccination in the adjuvant setting was safe and well-tolerated in PDA patients after tumor resection. A large-scale prospective study is warranted to evaluate the clinical benefit of this modality.

A 74-year-old man with interstitial lung disease (ILD) underwent surgical excision of a growing retroperitoneal tumor and was diagnosed with spindle cell sarcoma. Just after the surgery, skin eruption and muscle weakness emerged. Based on his symptoms and examination findings, we diagnosed him with anti-synthetase syndrome (ASS) with positive anti-glycyl-transfer ribonucleic acid synthetase antibody (anti-EJ) as paraneoplastic syndrome. Immunosuppressive treatments kept his progressing ILD stable for 21 months, although an expanding lung metastatic lesion from primary sarcoma was detected. Measurements of myositis-specific antibodies may enable the prediction of the efficacy of immunosuppressive treatments for paraneoplastic syndrome, even if the primary disease becomes progressive., Internal Medicine, 59(16), pp.2071-2076; 2020

The aim of the present study was to investigate whether LT candidates with sarcopenia are at an increased risk of receiving an inappropriate standard liver volume (SLV) estimation by standard body weight (BW)-derived SLV formula. Non-BW-SLV estimation formulas were tested in 262 LDLT donors and compared to a standard BW-SLV formula. The anthropometric parameters used were the thoracic width (TW-SLV) and thoracoabdominal circumference (TAC-SLV). Subsequently, sarcopenic and non-sarcopenic LDLT candidates (total, 217 patients) were compared in terms of estimated BW-SLV (routine method) and non-BW-SLV. In donors, TW-SLV showed comparable concordance with CT scan measured total liver volume as BW-SLV. The performance of TAC-SLV was low. In recipients, the prevalence of pre-LT sarcopenia was 30.4%. Sarcopenic patients were attributed a significantly lower BW-SLV than non-sarcopenic (sarcopenia vs no-sarcopenia, 1063.8 ml [1004.1-1118.4] vs. 1220.7 ml [1115.0-1306.6], P < 0.001), despite comparable TW-SLV, age, body height, and gender prevalence. As a result, sarcopenic patients received a graft with a statistically lower weight at organ procurement and developed more frequently a small-for-size syndrome (SFSS) according to the Dahm et al. (27.7% vs. 6.8%, P < 0.01) and Kyushu (28.7% vs. 9.2%, P < 0.01) definition. Therefore, In sarcopenic patients, BW-SLV formulas are affected by an high risk of SLV underestimation, thus exposing them to an increased risk of post-LT SFSS.

In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade

BACKGROUND: The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass (SMM). In living-donor liver transplantation (LDLT), liver graft regeneration (GR) represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient. Limited data are available on the correlation between pre-LDLT low SMM and GR. METHODS: Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft. The skeletal muscle index (SMI) at L3 level was used for muscle mass measurement, and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. GR was evaluated as rate of volume increase at 1 month post-LT [graft regeneration rate (GRR)]. RESULTS: The median GRR at 1 month post-LT was 91% (IQR, 65–128%) and a significant correlation with graft volume-to-recipient standard liver volume ratio (GV/SLV) (rho −0.467, P

Aim In human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients, the progression of liver failure is reported to be more aggressive than that in HCV mono-infected patients. Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+ -M2BP) is well recognized as a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We analyzed HIV/HCV coinfected patients' M2BP levels as a possible marker for predicting liver fibrosis. Methods M2BP was measured in 31 HIV/HCV coinfected patients, and we analyzed the correlation between WFA+ -M2BP and several markers of fibrosis, liver function, and tumor markers. We compared the WFA+ -M2BP levels in HIV/HCV coinfected patients with those of HCV mono-infected patients by performing a propensity score matching analysis. Results In the HIV/HCV coinfected patients, the serum level of WFA+ -M2BP was well correlated with the markers type IV collagen, hyaluronic acid, and alpha-fetoprotein, but not protein induced by vitamin K absence-II. In the propensity score matching with HCV mono-infected patients, the WFA+ -M2BP levels were significantly higher in the HIV/HCV coinfected patients compared with the levels in the HCV mono-infected patients. Conclusion In conclusion, WFA+ -M2BP might be a feasible predictive marker of fibrosis in HIV/HCV coinfected patients.

Objective This study aims to identify the most effective individual drug in an established triple-drug therapy (TDT) using a postoperative pancreatic fistula (POPF) rat model. Summary of background data POPF is the major complication of pancreatectomy that causes intraperitoneal abscess, sepsis, and pseudoaneurysm rupture, all of which may prolong hospital stays and cause potentially serious events or death. We previously demonstrated that TDT with a somatostatin analog, gabexate mesilate, and imipenem/cilastatin effectively prevents POPF, especially in high-risk patients. Methods POPF-induced rats were killed on postoperative day 3 after control (C), gabexate mesilate (G), imipenem/cilastatin (I), and somatostatin analog (S) treatments. Levels of serum amylase and lipase, or ascitic amylase and lipase were measured. Intraperitoneal adhesion between the abdominal wall and pancreas and pancreatic inflammation were evaluated. Results Serum amylase levels did not significantly differ among the groups. Serum lipase level was significantly higher in group I than in the other groups (P < 0.01). Both ascitic amylase and lipase levels were significantly lower in group S than in the other groups (P < 0.01). Median inflammation scores were significantly lower in groups G, I, and S than in group C (P < 0.01). Moreover, adhesion score was lower in group S than in the other groups (groups C, G, I, and S with scores 3, 2, 3, and 1, respectively, P < 0.01). Conclusion Among the 3 drugs, the somatostatin analog was the most effective against POPF.

Objective: In the treatment of advanced and recurrent colorectal cancer (ARCC), FOLFOXIRI regimens have been proven to be significantly superior to FOLFIRI in terms of the progression-free survival (PFS), response rate (RR), and overall survival (OS). Furthermore, the Tribe trial showed that the RR and PFS rates in patients who received bevacizumab (Bmab)+FOLFOXIRI were superior to those in patients treated with Bmab+FOLFIRI. A phase III trial of panitumumab (Pmab)+FOLFOXIRI is currently ongoing. A modified FOLFOXIRI regimen is also widely used to reduce adverse events. In our department, we introduced modified FOLFOXIRI+a (mFOLFOXIRI+a) in 2015. The present study reviewed the efficacy and safety of mFOLFOXIRI+a. Methods: Eligible patients were retrospectively reviewed, and their results were compared to those of patients treated with other regimens (OTHERS) (n=134) to demonstrate the efficacy of this treatment. Patients: Between February 2015 and November 2018, 12 patients with ARCC (male/female=6/6; average age, 60.7 years old) received mFOLFOXIRI+a (Bmab: 10, Pmab: 1, alone: 1). Results: The median PFS in the mFOLFOXIRI+a and OTHERS groups was 565 and 322 days, respectively (p=0.0544). The RR in the mFOLFOXIRI+a and OTHERS groups was 66.7% and 31.3%, respectively (p= 0.0135). The conversion rate (Conv R) in the mFOLFOXIRI+a and OTHERS groups was 50.0% and 12.7%, respectively (p=0.0007). While 58% of patients treated with FOLFOXIRI+a developed grade >3 leukopenia, the incidence of febrile neutropenia (FN) was only 17%. In all patients with symptoms due to the tumor burden, the symptoms subsided with mFOLFOXIRI+a treatment. Conclusion: Based on the RR, Conv R, and symptom palliation ability, mFOLFOXIRI+a was suggested to be a viable candidate for first-line treatment for patients with ARCC, especially those with a high tumor burden., Internal medicine, 59(10), pp.1239-1245; 2020

Background Hepatic artery thrombosis can lead to graft loss associated with severe hepatic infarction or bile duct ischemia. When anatomical hepatic artery reconstruction is impossible in liver transplantation or hepato-pancreatic biliary surgery, portal vein arterialization (PVA) is proposed as a salvage technique. Herein, we report our experience with a case that showed favorable clinical outcomes after partial PVA during living-donor liver transplantation (LDLT) because of difficulties in arterial reconstruction. Case presentation A 62-year-old woman with non-B, non-C liver cirrhosis complicated with hepatocellular carcinoma was being prepared for LDLT using an extended left lobe graft. The graft presented with two arteries (left hepatic artery, 2 mm; middle hepatic artery, 2 mm). The first anastomosis was performed using the recipient hepatic artery stumps, but no flow was detected on Doppler control because of thrombus formation. The next attempt was executed using the middle colic artery with a radial artery jump graft and the right gastroepiploic artery, but it led to the same result. Thus, the graft oxygen support by the standard arterial procurement was abandoned, and a shunt was created between the ileocecal artery and the vein to obtain PVA. Arteriography of the superior mesenteric artery showed that the shunt was relatively patent, and the portal vein was apparent. No biliary complication or liver abscess occurred postoperatively, and the patient presented with good liver function and no complications related to portal vein hypertension, nor liver fibrosis 18 months after the LDLT. Conclusion Partial PVA with a shunt created between the ileocecal artery and the vein is useful when arterial reconstruction is difficult during LDLT for preventing graft loss caused by severe hepatic infarction or bile duct ischemia.

Introduction: Cell sheets consisting of adipose-derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the efficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. Methods: Eleven female pigs (20?25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL-labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were isolated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently transplanted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, infiltration of inflammatory cells, and collagen content. Results: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of inflammatory cells and more collagen fibers were identified in the bile duct wall. Conclusions: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the efficacy of this mechanism in prevention of biliary anastomotic strictures., Regenerative Therapy, 14, pp.79-86; 2020

Superior mesenteric artery syndrome can lead to duodenal obstruction due to vascular compression. We treated a patient with superior mesenteric artery syndrome by performing a complete laparoscopic duodenojejunostomy with a linear stapled closure of the common enterotomy. A 72-year-old woman presented with nausea, vomiting, and weight loss. CT revealed superior mesenteric artery syndrome. Conservative management was not effective. Because the patient required a surgical bypass for long-term relief, a laparoscopic duodenojejunostomy was performed. In past cases, hand-sewn sutures were made through a small incision to avoid stenosis when the common enterotomy was closed. For our patient, we closed the common enterotomy with a linear stapler in a complete laparoscopic maneuver. We performed the closure after placing several temporary sutures to minimize the amount of intestinal wall to be removed. Laparoscopic duodenojejunostomy is a minimally invasive procedure, and a linear stapled closure of a common enterotomy is a safe surgical technique that reduces invasiveness.

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.

Background Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179. Registered on 9 April 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3332-5) contains supplementary material, which is available to authorized users.

Aim It is reportedly difficult to accurately assess the liver reserve capacity of patients with HIV/hepatitis C virus (HCV) co-infection through contaminated blood products by the Child-Pugh (CP) classification. Therefore, we investigated a clinically applicable scoring system in determining the risk of esophageal varices in HIV/HCV co-infected patients, known as latent portal hypertension leading to esophageal varices. Methods Forty-three patients with HIV/HCV co-infection underwent clinical examinations, including endoscopy and assessment of hepatic reserve, in our department between 2009 and 2017. Child-Pugh score, the recently developed albumin-bilirubin (ALBI) grade, and the albumin-indocyanine green evaluation (ALICE) were compared to evaluate their diagnostic accuracy for the detection of esophageal varices using the area under the receiver operating characteristic curve (AUROC). Results The patients were all male hemophiliacs and were positive for both HIV and HCV antibodies, with a median age of 45 years (range, 29-66 years). Thirty-seven patients (84.1%) were classified as CP A at the examination. The comparison of AUROCs showed a superior diagnostic accuracy for ALICE (AUROC = 0.814) to detect esophageal varices. The positive prediction rate was the highest with ALICE if -2.325 was set, and the negative prediction rate was the highest with ALBI if -2.575 was set. The ALICE showed the highest accuracy compared to other two scores. Conclusion The ALICE score was found to be the most valuable system for portal hypertension in HIV/HCV co-infected hemophilia patients. Because of its high specificity, ALICE for secondary surveillance could be used after other markers such as the aspartate aminotransferase to platelet ratio index and Fibrosis-4 index.

Objective/Background: Huge aneurysm of the visceral artery is rare and a treatment strategy for such cases has not yet been established. Here, we report a case of huge aneurysm of the common hepatic artery (44-mm diameter) successfully treated by stent placement. Methods: A 77-year-old female patient was referred to our department due to growth of the common hepatic artery aneurysm. The cause of the aneurysm was suspected to be segmental arterial mediolysis. Due to the possibility of a spontaneous rupture, we decided to stent the common hepatic artery. Result: We had some difficulties during the procedure, such as thrombosis of the stent, and it was necessary to insert an additional stent. The procedure was effective and the patient has been doing well without any complications at the 6-year follow-up. Conclusion: Stenting is possible and effective in cases of huge aneurysm of the common hepatic artery., Radiology Case Reports, 14(1), pp.44-47; 2018

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.

Acute cholecystitis is a progressive inflammation of the gallbladder usually caused by gallstones obstructing the cystic duct. Congestion and edema are evident symptoms during the first 2-4 days, also known as the phase of edematous cholecystitis. Necrotizing cholecystitis, a phase characterized by bleeding and necrosis, is seen at 3-5 days. From 7-10 days, the disease progresses to its purulent phase, also known as suppurative cholecystitis. If the disease is still left untreated at this point, it progresses to subacute cholecystitis and it eventually becomes chronic cholecystitis. Possible complications that affect the management of cholecystitis include perforation of the gallbladder (bile peritonitis) during the hemorrhagic and necrosis phase, and peri-gallbladder abscess and internal biliary fistula during the purulent phase.

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.

Liver transplantation, the only proven treatment for end-stage liver disease and acute liver failure, is hampered by the scarcity of donors. Regenerative medicine provides an alternative therapeutic approach. Tremendous efforts dedicated to liver regenerative medicine include the delivery of transplantable cells, microtissues, and bioengineered whole livers via tissue engineering and the maintenance of partial liver function via extracorporeal support. This brief review summarizes the current status of regenerative medicine for the hepatobiliary system. For liver regenerative medicine, the focus is on strategies for expansion of transplantable hepatocytes, generation of hepatocyte-like cells, and therapeutic potential of engineered tissues in liver disease models. For biliary regenerative medicine, the discussion concentrates on the methods for generation of cholangiocyte-like cells and strategies in the treatment of biliary disease. Significant advances have been made in large-scale and long-term expansion of liver cells. The development of tissue engineering and stem cell induction technology holds great promise for the future treatment of hepatobiliary diseases. The application of regenerative medicine in liver still lacks extensive animal experiments. Therefore, a large number of preclinical studies are necessary to provide sufficient evidence for their therapeutic effectiveness. Much remains to be done for the treatment of hepatobiliary diseases with regenerative medicine.

The authors describe the first case of simultaneous liver and kidney transplantation (SLK) in a human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patient with severe hemophilia in Japan, and it could be second case in the world. The patient was a 61-year-old Japanese man with HCV cirrhosis complicated with HIV coinfection through contaminated blood product for hemophilia B at age 1 year. The patient's liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 38. He had been on hemodialysis for 6 years, but HIV RNA and HCV RNA had been undetectable after appropriate antiviral therapies. In September 2019, the patient underwent successful deceased donor (DD) SLK. The donor was a man in his 60s deceased due to cerebral hemorrhage. Regular DD liver transplantation was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 566 min, and the graft liver weighed 1154 g. The graft kidney was transplanted extraperitoneally in the right iliac fossa. The administration of clotting factor IX was discontinued on day 3. The immunosuppressive regimen was based on intravenous induction with 2 mg/kg of basiliximab and 1 g methylprednisolone and subsequent oral administration of mycophenolate mofetil and prednisolone, followed by low-dose tacrolimus after 1 week for kidney-sparing purpose. Steroid therapy was gradually discontinued at 3 months after SLK. The same pretransplantation antiretroviral therapy (ART; tenofovir and dolutegravir) was introduced after 3 days when the CD4 cell count was more than 300/μL and HIV RNA was within an undetectable range. The postoperative course was uneventful without infectious complication, and the patient was transferred to a referral hospital on day 90 and discharged home on day 111. Strategic surgical planning and meticulous pre- and post-transplant management of ART and clotting factors could lead to the success of SLK.

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

We herein report an effective procedure for liver transplantation (LT) for severe cirrhotic patients with hemophilia. Three hemophilic patients suffering from liver cirrhosis due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection underwent deceased donor LT in our institute. Basic clotting parameters were measured and evaluated during LT to determine the optimal packing procedure. All patients were treated with a gauze packing procedure to ensure stable hemostasis in relation to hemophilia during the peri-transplant period. The graft function of all patients recovered well upon gauze removal (depacking) procedure and the patients were finally discharged to home. The administration of clotting factor was discontinued on day 3 after deceased donor LT. No infectious complications occurred in any of the 3 patients. This technique could be an option for achieving successful LT in these patients. Cooperation between transplant surgeons and anesthesiologists can make this challenging operation possible.

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.

Background: Liver transplantation is indicated for patients with Wilson’s disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). Case Report: A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal 20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE). The model for end-stage liver disease (MELD) score was 35. Due to her critical condition, the patient underwent LDLT utilizing a right liver graft from her 44-year-old mother. The right hepatic vein (RHV) and inferior right hepatic vein (iRHV) were reconstructed. She developed severe liver dysfunction due to a crooked hepatic vein caused by compression from the large graft. To straighten the bend, a reoperation was performed. During the operation, we tried to relieve the compressed hepatic vein by adjusting the graft location, but the benefits were limited. We therefore performed stenting in both the RHV and iRHV on postoperative day 9. The patient gradually improved, exhibiting good liver and renal functions, and was finally discharged on postoperative day 114. Conclusions: When WD-FHF deteriorates too rapidly for conservative management, LDLT is an effective therapeutic strategy., American Journal of Case Reports, 19, pp.304-309; 2018

AIM Infection is a frequent cause of in-hospital mortality after liver transplantation (LT). Elimination of possible risks in the pretransplant period, early diagnosis of post-transplant sepsis, and prompt treatment with antimicrobial agents are important. The objectives of this study were to analyze the impact of early post-transplant sepsis on outcomes and to clarify the value of predictive factors for early post-transplant sepsis. METHODS The study included 136 patients who underwent initial living donor LT (LDLT) at our institute between April 2009 and December 2016. Sepsis was defined using the third international consensus criteria. The results of biochemical tests at the introduction of anesthesia before LDLT were collected for pretransplant evaluation. RESULTS Post-transplant sepsis was found in 37 patients (27.2%). More patients had a pre-transplant serum procalcitonin (PCT) level >0.5 ng/mL in the sepsis group than in the non-sepsis group (11 [29.7%] vs 10 [10.1%]; P = 0.007). The 1-year survival rate in the sepsis group was significantly lower than in the non-sepsis group (53.8% vs 87.2%; P 0.5 ng/mL (odds ratio, 3.8; 95% confidence interval, 1.3-10.9; P = 0.01) as the only independent risk factor for post-transplant sepsis. CONCLUSIONS Survival of patients with early post-transplant sepsis was poor and the incidence of sepsis was associated with the pretransplant serum PCT level. Re-evaluation of the general condition and rescheduling of LT should be considered in a patient with pretransplant serum PCT >0.5 ng/mL.

Introduction: A malignant tumor invading the inferior vena cava (IVC) and concomitant with 3 hepatic venous involvement still remains surgical therapeutic challenge. Presentation of case: A 79-year-old male presented with liver dysfunction and was eventually diagnosed with an intrahepatic huge IHCC originating at the level of confluence of 3 hepatic veins to the IVC, extending to the right hepatic vein (HV). Under extracorporeal circulation, the liver with the IVC, portal vein,hepatic artery and common bile duct were removed en bloc. In the back table, the left liver lobe was resected including the tumor and IVC, and the right HV was reconstructed using the patient's reversed left renal vein (LRV) and IVC graft. Subsequently, the patient's right liver lobe with the reversed LRV/IVC graft was transplanted back into the patient using a partial liver transplant technique. Liver enzymes gradually came down to the value within normal range on postoperative day 13 with the patency of the right HV. However, the patient expired on POD 16 because of sudden septic complications. Discussion: This technique could be one of the options to reconstruct the HV/IVC when a tumor invades all 3 HVs. Conclusion: To the best of our knowledge, this is the first report of such HV reconstruction in combination with extracorporeal resection of huge liver cancer in updated world literature., International Journal of Surgery Case Reports, 57, pp.57-59; 2019

Pharmacologic thromboprophylaxis is recommended for preventing pulmonary embolism according to some abdominal surgery guidelines. However, few reports have so far described pharmacologic thromboprophylaxis after pancreatic surgery. In addition, concern remains regarding postoperative bleeding due to pharmacologic thromboprophylaxis. We investigated the safety and efficacy of enoxaparin, a low-molecular-weight heparin, as postoperative pharmacologic thromboprophylaxis after pancreatic surgery. In this record-based retrospective study, the sample population comprised 151 consecutive patients who underwent pancreatic surgery and received enoxaparin postsurgery at our institute between November 2009 and March 2014. The primary outcome was the incidence of symptomatic pulmonary embolism after surgery, and the secondary outcome was the incidence of bleeding as an adverse effect of enoxaparin injection. No symptomatic pulmonary embolism events occurred during the study. Major and minor bleeding events were experienced in 5 (3.3%) cases each. Four of these major events were caused by the rupture of a pseudoaneurysm with a pancreatic fistula not related to enoxaparin, and all events were treated safely with no mortalities in the study period. We found no factors related to minor bleeding with enoxaparin injection in a statistical comparison. The use of enoxaparin is considered to be safe and effective for pulmonary embolism prophylaxis after pancreatic surgery.

Aim We examined the feasibility of the aspartate transaminase (AST)–platelet ratio index (APRI) and Fibrosis-4 (FIB4) score, which are well-established markers for liver fibrosis, as indicators for monitoring esophageal varices in patients who were co-infected with HIV and hepatitis C virus (HCV) due to contaminated blood products for hemophilia in Japan. Methods Forty-three HIV/HCV co-infected patients were enrolled. All were hemophilic men (median age 41 years; range, 29–66 years). We analyzed the correlations between fibrosis indices (APRI, FIB4) and various liver function tests, fibrosis markers, liver stiffness measured by acoustic radiation force impulse elastography, and the findings of gastrointestinal endoscopy. Results Both APRI and FIB4 were well correlated with several of the factors related to liver fibrosis and the existence of esophageal varices in the patients. The cut-off values for detecting esophageal varices estimated as the area under the receiver operating characteristic curve were 0.85 for APRI and 1.85 for FIB4. Conclusion In patients co-infected with HIV/HCV due to contaminated blood products for hemophilia, APRI and FIB4 are effective for monitoring esophageal varices, even among patients who are apparently doing well with good liver function as Child–Pugh grade A.

Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program. We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor. The purposes of the DAT program are as follows: To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

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.

Background: Simultaneous pancreas-kidney transplantation (SPK) is an established therapy for diabetes mellitus (DM) patients with associated end stage renal disease. We report the initial results of SPK in our institution afterqualification as transplantation program. Patients and methods: Between September 2017 and July 2018, we performed 3 SPK in type 1 diabetic patientswith end-stage renal disease. All grafts were procured from brain-dead marginal donors according Pittsburgcriteria. Results: The recipients were 2 men and 1 woman with a mean age of 43 ± 5.4 years. Mean time from DMdiagnosis and time on dialysis were 25.7 ± 3.9 years and 19.7 ± 9.1 months. The mean age and HbA1C valueof donor were 56.7 ± 0.5 years and 5.67 ± 0.05%. The pancreatic grafts were transplanted intraperitoneally inthe right iliac fossa. Two patients required a relaparotomy due to arterial anastomotic hemorrhage and twopatients developed acute cellular rejection. With a median follow-up of 13 (6?15) months, patient's and graft'ssurvival rate were 100%. All patients showed HbA1C within normal range, but oral glucose tolerance testshowed DM pattern in two patients at 3 months after transplantation. Conclusions: In our initial experience with SPK, mid-term grafts and patient survival appear comparable to theresults reported in literature. Despite the limited availability of donors and the use of grafts from marginaldonors, a quality pancreas transplantation program can be established even in a small-volume centers. Nonetheless further improvement in surgical techniques and meticulous management appear mandatory., Transplantation Reports, 4(2), art.no.100029; 2019

A 12-year-old girl underwent LDLT using a left lobe graft for hepatic dysfunction associated with citrin deficiency. A continuous anastomosis suture technique was performed between the recipient's IVC and the donor's left hepatic vein. At age 14, the patient developed intractable ascites. Venography of the IVC and hepatic vein showed twisted-shape stenosis of the hepatic vein-IVC anastomosis with intravascular pressure gradient, probably due to the enlarged transplanted liver, for which a metallic stent was placed. The ascites disappeared, and the patient was making satisfactory progress eight months after surgery. However, nine months after surgery, the ascites appeared again with edema in the lower extremities. Since the stent that had been inserted was suspected of hampering the outflow of the graft liver and IVC, it was decided to conduct stent removal and IVC angioplasty. After intravascular exploration, the stent was removed. Angioplasty was performed. An autologous vascular graft patch was designed to be wedge-shaped to fit the incised part of the IVC, and it was sutured with 5-0 non-absorbable surgical sutures using a continuous suture technique. No postoperative complications or perioperative graft dysfunction were observed. The ascites decreased markedly, and the edema in the lower extremities disappeared. Thus, we were able to successfully perform IVC angioplasty using an autologous vascular graft patch in a patient who developed IVC stenosis after stenting. This procedure is one of the most effective treatment options, especially for pediatric patients requiring long-term vascular patency.

Introduction Laparoscopic-endoscopic cooperative surgery (LECS) is a minimally invasive surgical technique that combines the advantages of laparoscopic surgery and endoscopic treatment. LECS has been developed for treatment of gastric submucosal tumors and can be applied to superficial non-ampullary duodenal tumors. Here we describe the use of LECS for duodenal mucosal cancer. Materials and Surgical Technique After the placement of five ports, an endoscopic procedure was performed to confirm the tumor location and to place marks around the tumor. The jejunum was then resected 10 cm from the ligament of Treitz, and the connective tissue between the pancreas and duodenum was dissected to close to Vater's papilla. Duodenal resection was performed with a stapling device 2 cm to the oral side of the tumor, with endoscopic confirmation of the duodenal papilla, and duodenal tubular resection was then accomplished. Duodeno-jejunostomy was carried out using the same stapling device. There were no postoperative complications. Discussion This case shows that duodenal tubular resection using LECS enables curability through a minimally invasive procedure that offers the advantages of laparoscopic surgery and endoscopic treatment. This technique is applicable to duodenal lesions such as those due to duodenal mucosal cancers.

Neoadjuvant therapy (NAT) is increasingly used to improve the prognosis of patients with borderline resectable pancreatic cancer (BRPC) albeit with little evidence of its advantage over upfront surgical resection. We analyzed the prognostic impact of NAT on patients with BRPC in a multicenter retrospective study. Medical data of 165 consecutive patients who underwent treatment for BRPC between January 2010 and December 2014 were collected from ten institutions. We defined BRPC according to the National Comprehensive Cancer Network guidelines, and subclassified patients according to venous invasion alone (BR-PV) and arterial invasion (BR-A). The rates of NAT administration and resection were 35% and 79%, respectively. There were no significant differences in resection rates and prognoses between patients in the BR-PV and BR-A subgroups. NAT did not have a significant impact on prognosis according to intention-to-treat analysis. However, in patients who underwent surgical resection, NAT was independently associated with longer overall survival (OS). The median OS of patients who underwent resection after NAT (53.7 months) was significantly longer than that of patients who underwent upfront (17.8 months) or no resection (14.9 months). The rates of superior mesenteric or portal vein invasion, lymphatic invasion, venous invasion, and lymph node metastasis were significantly lower in patients who underwent resection after NAT than in those who underwent upfront resection despite similar baseline clinical profiles. Resection after NAT in patients with BRPC is associated with longer OS and lower rates of both invasion to the surrounding tissues and lymph node metastasis.

Although carbon-ion radiotherapy (CIRT) has been reported to achieve good local control of hepatocellular carcinoma (HCC), liver transplantation is still required in patients with tumor recurrence. However, few cases of living donor liver transplantation (LDLT) after curative CIRT for HCC has been reported. It would be of great interest to ascertain the true situation of the irradiated region as well as to clarify the surgical points. We herein report the surgical findings and our experience along with technical difficulties and knacks concerning two cases of LDLT for HCC after CIRT. Both patients suffered tumor recurrence after curative CIRT for HCC. Severe adhesions were found between the irradiated region and the surrounding tissues, which resulted in surgical difficulties. Histological findings showed severe tissue fibrosis in the CIRT area. We should pay attention to adhesions in the irradiated area caused by CIRT including the vascular reconstruction during surgery.

Purpose: Despite refinements in surgical techniques for liver resection, evaluation of hepatic reserve disparity remains one of the most common problems in liver surgery, especially for hepatic malignancies such as hepatocellular carcinoma (HCC). Portal venous pressure (PVP) is regarded one of the important factors in selecting treatment strategy, although its measurement can be invasive and complex. Methods: To establish a formula for calculating PVP preoperatively, intraoperative directly measured PVP was used in 177 patients with preoperative factors and liver function tests such as age, sex, virus status, platelet count, prothrombin time, albumin, total bilirubin, alanine aminotransferase (ALT), Child?Pugh grade, liver damage defined by the Liver Cancer Study Group of Japan, indocyanine green retention rate at 15 min (ICG-R15), and the aspartate transaminase (AST)-platelet ratio index (APRI). Results: Although 90% of the patients were classified as Child-Pugh A, median direct PVP was 16.5 cm H2O (5.5?37.0) and the percentage of PVP greater than 20 cm H2O was 27.1%, reflecting portal hypertension due to liver damage. After multiple regression analysis, the formula PVP (cmH2O) = EXP[2.606 + 0.01 × (ICG-R15) + 0.015 × APRI] was established from the measured data. Conclusion: Considering its simplicity of use, we have adopted this formula for predicting PVP in determining treatment strategy for HCC and other hepatic malignancies., Journal of Investigative Surgery, Article in Press

Intraoperative hyperglycemia during liver transplantation can induce infectious bacterial complications after surgery. The aim of this study was to evaluate the efficacy of the artificial endocrine pancreas in achieving perioperative blood glucose control and preventing infection in patients undergoing living donor liver transplantation (LDLT). We compared 14 patients with an artificial endocrine pancreas device to 14 patients who underwent glycemic control using the sliding scale method with respect to perioperative blood glucose level and postoperative infection. In this study, we aimed to control the perioperative glucose levels consecutively for 24 hours from the induction of anesthesia. The average blood glucose level in the artificial pancreas group was significantly lower than that in the sliding scale group (118 vs. 141 mg/dL, P < 0.05). The postoperative bacterial infection rate of the artificial pancreas group was significantly lower than that of the sliding scale group within one month after LDLT (35.7% vs. 78.6%, P < 0.05). Multiple regression analysis showed non-application of artificial endocrine pancreas as a significant risk factor of posttransplant infection. The artificial endocrine pancreas enabled the perioperative glucose level to be stably controlled without hypoglycemia. Artificial pancreas may reduce the incidence of postoperative infection after LDLT.

Background and aim: pancreatic juice cytology (PJC) is an important predictor of malignant intraductal papillary mucinous neoplasm (IPMN). This study aimed to determine the role of PJC for the prediction of malignant IPMN (intraductal papillary mucinous cancer [IPMC]). Methods: medical records of IPMN patients who underwent surgery between 2012 and 2016 at the Nagasaki University Hospital were reviewed. Patients who underwent preoperative PJC were classified as high risk stigmata (HRS), worrisome features (WF) and no-criteria, based on imaging criteria. PJC class III or higher was considered as positive and only invasive IPMN was defined as IPMC. PJC was validated in each group with regard to sensitivity, specificity, accuracy with the corresponding 95% confidence intervals (95% CI) and area under receiver operating curve (AUROC) analysis. A p-value of < 0.05 was considered as statistically significant. Results: preoperative pancreatic juice was obtained in 33/52 IPMN patients; only patients with adequate aspirate for cytology (n = 29) were included. In the HRS group (n = 9), 4/6 non-IPMC had a negative PJC and 3/3 IPMC had a positive PJC. In the WF group (n = 17), 9/11 non-IPMC had a negative PJC and 3/6 IPMC had a positive PJC. Adding PJC to imaging results improved the AUROCs of HRS and WF from 0.63 and 0.62 to 0.83 and 0.66, respectively. PJC was negative in all no-criteria cases (n = 3; one IPMC and two non-IPMC). In all 29 patients, PJC sensitivity was 60% (95% CI: 26%-88%), specificity was 79% (95% CI: 54%-94%), accuracy was 72% (95% CI: 63%-89%) and the AUROC was 0.69 (p = 0.03). Conclusion: PJC is a statistically significant IPMC predictor that can improve the validity of imaging for IPMC prediction.

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

It is well known that the presence of end-stage liver disease increases the risk of developing hepatocellular carcinoma (HCC). Liver transplantation (LT) for patients within the Milan criteria has become a standard treatment for HCC in most developed centers worldwide. However, a major cause of death in cirrhotic patients with HCC after transplantation is tumor recurrence, including peritoneal recurrences, which develops rarely but presents a significant problem with regard to their management. Our experience includes two cases with HCC within the Milan criteria of peritoneal recurrences after living donor LT. Both patients had interventions for HCC in their medical history before LT, and we propose that these might have been a possible cause of the HCC peritoneal recurrence., Case Reports in Gastroenterology, 9(1), pp.29-35; 2015

Background: The impact of treated preoperative bacterial infections on the outcome of living-donor liver transplantation (LDLT) is not well defined. The aim of this study was to determine the frequency of pre-transplant bacterial infections within one month before LDLT and their impact on the post-transplant morbidity and mortality. Material/Methods: We retrospectively reviewed the records of 50 adult LDLT recipients between January 2009 and October 2011. Patients were divided into two groups based on whether they had episodes of bacterial infections within one month before LDLT. Results: There were 20 patients who required antimicrobial therapy for pre-transplant infections. The pre-transplant infections comprised urinary tract infections (35%), cholangitis (10%), pneumonia (10%), bacteremia (5%), spontaneous bacterial peritonitis (5%), acute sinusitis (5%), subcutaneous abscess (5%), and empirical treatment (25%). Patients with pre-transplant infections had higher Child-Pugh scores [median, 11 vs. 9.5, P, Annals of Transplantation, 19, pp.674-679; 2014

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

We previously reported that progression of liver cirrhosis is quicker and survival is dismal in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection, especially when acquired in childhood through contaminated blood products. Recently, we performed the first deceased donor liver transplantation (DDLT) for an HIV/HCV-coinfected hemophilic patient in Japan. A 40-year-old man was referred to our hospital for liver transplantation. Regular DDLT was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 465 min, and the graft liver weighed 1,590 g. The antiretroviral therapy (ART) was switched from darunavir/ritonavir to raltegravir before the transplant for flexible usage of calcineurin inhibitors postoperatively; tenofovir was used as the baseline treatment. The postoperative course was uneventful, and the patient was discharged home on day 43. He started receiving anti-HCV treatment on day 110 with pegylated interferon, ribavirin, and simeprevir after the DDLT. Herein, we report the first case of DDLT in Japan. Meticulous management of ART and clotting factors could lead to the success of DDLT., Japanese Journal of Infectious Diseases, 69(1), pp.80-82; 2016