Search

Summary: Background: Delayed gastric emptying (DGE) is uncomfortable complication after left hepatectomy. The aim of this study is to show our strategy to prevent DGE after living donor left hepatectomy. Methods: The cases were divided into 3 groups as without any prevention (control group), prevented DGE with putting omentum between the liver and pylorus (O group), and with putting a Seprafilm (S group). The incidence of DGE and the CT finding 1 month after surgery were retrospectively compared between the groups. Results: The incidence of DGE was significantly decreased in O and S group than control group (P

The molecular mechanisms underlying the conspecific cue-mediated larval settlement in Crassostrea gigas is not yet fully understood. In this study, we described and compared the tran-scriptomes of competent pediveligers (Pedi) and conspecific cue-induced postlarvae (PL). A total of 2383 candidate transcripts were identified: 740 upregulated and 1643 downregulated transcripts, after settlement. Gene Ontology analysis revealed active chitin binding, calcium ion binding, and extracellular region processes in both stages. Results showed that the differential expression trend of six candidate transcripts were consistent between the quantitative real-time PCR and transcriptome data. The differential transcript expression related to shell formation showed closely linked dynam-ics with a gene regulatory network that may involve the interplay of various hormone receptors, neurotransmitters, and neuropeptide receptors working together in a concerted way in the Pedi and PL stages. Our results highlight the transcriptome dynamics underlying the settlement of oysters on conspecific adult shells and demonstrate the potential use of this cue as an attractant for wild and hatchery-grown oyster larval attachment on artificial substrates. It also suggests the possible in-volvement of an ecdysone signal pathway that may be linked to a neuroendocrine-biomineralization crosstalk in C. gigas settlement., Annals of Transplantation, 27, art. no. e936371; 2022

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 integration of a bile drainage structure into engineered liver tissues is an important issue in the advancement of liver regenerative medicine. Primary biliary cells, which play a vital role in bile metabolite accumulation, are challenging to obtain in vitro because of their low density in the liver. In contrast, large amounts of purified hepatocytes can be easily acquired from rodents. The in vitro chemically induced liver progenitors (CLiPs) from primary mature hepatocytes offer a platform to produce biliary cells abundantly. Here, we generated a functional CLiP-derived tubular bile duct-like structure using the chemical conversion technology. We obtained an integrated tubule-hepatocyte tissue via the direct coculture of hepatocytes on the established tubular biliary-duct-like structure. This integrated tubule-hepatocyte tissue was able to transport the bile, as quantified by the cholyl-lysyl-fluorescein assay, which was not observed in the un-cocultured structure or in the biliary cell monolayer. Furthermore, this in vitro integrated tubule-hepatocyte tissue exhibited an upregulation of hepatic marker genes. Together, these findings demonstrated the efficiency of the CLiP-derived tubular biliary-duct-like structures regarding the accumulation and transport of bile.

Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H. bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H. bilis on cholangiocytes, focusing on inflammation and oxidative stress.Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H. bilis infection.Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H. bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4 pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p .05). MMNK-1 proliferation was also significantly higher in H. bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H. bilis (1.0 vs. 1.17 ± 0.06, p .05); however, DNA injury was not observed in cocultures with H. bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/μl, p = .06).Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.

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.

Aim In the aging society, understanding the influence of hepatocyte age on hepatocyte donation may inform efforts to expand alternative cell sources to mitigate liver donor shortage. A combination of the molecules Y27632, A-83-01, and CHIR99021 has been used to reprogram rodent young hepatocytes into chemically induced liver progenitor (CLiP) cells; however, whether it could also reprogram aged hepatocytes has not yet been elucidated. Methods Primary hepatocytes were isolated from aged and young donor rats, respectively. Hepatic histological changes were evaluated. Differences in gene expression in hepatocytes were identified. The in vitro reprogramming plasticity of hepatocytes as evidenced by CLiP conversion and the hepatocyte and cholangiocyte maturation capacity of reprogrammed CLIPs were analyzed. The effect of hepatocyte growth factor (HGF) on cell propagation was also investigated. Results The histological findings revealed ongoing liver damage with inflammation, fibrosis, senescence, and ductular reaction in aged livers. Microarray analysis showed altered gene expression profiles in hepatocytes from aged donors, especially with regard to metabolic pathways. Aged hepatocytes could be converted into CLiPs (Aged-CLiPs) expressing progenitor cell markers, but with a relatively low proliferative rate compared with young hepatocytes. Aged-CLiPs possessed both hepatocyte and cholangiocyte maturation capacity. HGF facilitated CLiP conversion in aged hepatocytes, which was partly related to the activation of Erk1 and Akt1 signaling. Conclusions Aged rat hepatocytes have retained reprogramming plasticity as evidenced by CLiP conversion in culture. HGF promoted proliferation and CLiP conversion in aged hepatocytes. Hepatocytes from aged donors may be used as an alternative cell source to mitigate donor shortage.

Introduction Acetaminophen has been widely used as an analgesic agent after various types of surgery. However, acetaminophen may sometimes induce severe liver dysfunction, which can occasionally lead to the need for liver transplantation. The aim of this study was to assess the feasibility and efficacy of administering acetaminophen to patients after liver resection (LR). Patients and methods The prospective study included 50 patients who underwent the following procedures: partial LR (n = 21) and more than one section LR (n = 29). Pain control was provided with continuous intravenous fentanyl and acetaminophen every 6 hours (within 2 days). We analyzed the liver function and blood concentration of acetaminophen at 1 and 3 days after LR using high performance liquid chromatography (HPLC), and investigated the results of partial and more than one section LR, and also examined the degree of liver fibrosis. Results The alanine transaminase level on postoperative days 1, 5, and 7 and total bilirubin on postoperative days 1 to 5 after LR in patients with more than one section LR was significantly higher than the levels in patients with partial resection. No patients developed liver failure. The blood concentration of acetaminophen by HPLC was significantly elevated in patients with resection of more than one section in comparison to the partial resection group. Conclusion The safety of acetaminophen was evaluated in Japanese patients who underwent different types of LR with different degrees of liver fibrosis.

692 Background: Patients with ampulla of Vater carcinoma with lymph node metastasis reportedly have a poor prognosis and require postoperative adjuvant therapy. However, due to the small number of published cases, the efficacy of postoperative adjuvant therapy has not yet been established with a high level of evidence. Objective: The aim of this study was to describe the outcome of patients surgically treated for ampulla of Vater carcinoma in our department, evaluate the effectiveness of adjuvant chemotherapy (AC), and clarify which patient groups may benefit from AC. Methods: The study cohort comprised 46 patients who underwent surgery for ampulla of Vater carcinoma in our department from October 2005 to March 2022. We evaluated the clinicopathological background characteristics (tumor size, gross morphology, pancreatic/duodenal invasion, peripancreatic head lymph node metastasis), overall survival (OS), and relapse-free survival (RFS), and compared the OS and RFS in patients with versus without AC. We then analyzed the factors related to the long-term outcome of patients treated for ampulla of Vater carcinoma. Results: During a median observation period of 33.7 months, the 5-year OS and RFS were 63.1% and 61.7%, respectively. Recurrence was observed in 14 patients (30%), with recurrence occurring less than 1 year postoperatively in seven patients (15%). Fifteen patients received AC (chemotherapy regimen: S-1 in 11 patients, GEM in four). The 5-year OS rates with and without AC were 70.3% and 48.2%, respectively (p=0.093). The 5-year RFS rates with and without AC were 72.5% and 42.8%, respectively (p=0.058). Univariate analysis of the total patient cohort showed that the factors related to 5-year RFS were pancreatic invasion (p=0.01), duodenal invasion (p=0.03), and N+ (p=0.004). In multivariate analysis, the only factor related to 5-year RFS was N+ (HR 3.53; 95% CI, 0.99–12.6; p=0.03). The 5-year OS rates in patients with and without N+ were 77.1% and 42.7%, respectively (p=0.04). The 5-year RFS rates in patients with and without N+ were 80.4% and 32.1%, respectively (p=0.004). Conclusions: AC showed a tendency to be effective in preventing postoperative recurrence of ampulla of Vater carcinoma. AC may be particularly beneficial in N+ cases.

The length of hospital stay is an important outcome measure in patients who have undergone pancreaticoduodenectomy. Although postoperative complications are known to adversely affect the length of hospital stay (LOS), the influence of early mobilization on LOS has not been clarified yet. This study aimed to examine the impact of the initial ambulation day, which is one of the components of early mobilization, on LOS after pancreaticoduodenectomy. We retrospectively enrolled patients who underwent pancreaticoduodenectomy between January 2013 and December 2017. Postoperative complications were evaluated using the Clavien–Dindo classification (CDC) system. Patients were divided into two groups based on the median LOS (early and late-discharge groups) and compared to determine their characteristics. Multivariate logistic regression analysis was performed with LOS as the dependent variable. Patients in the late-discharge group were significantly older, had an initial ambulation delay, and had higher rates of advanced disease stages and a CDC grade ≥ IIIa than those in the early discharge group. In the multivariate logistic regression analysis, CDC grade ≥ IIIa, initial ambulation day, and age were found to be significant independent factors associated with LOS. Our results demonstrated that not only postoperative complications, but also the initial ambulation day, could affect LOS after pancreaticoduodenectomy, emphasizing the importance of early ambulation for patients who undergo this surgery., Tohoku Journal of Experimental Medicine, 254(4), pp. 287-294; 2021

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.

Chemically induced liver progenitor (CLiP) cells, converted in vitro from mature hepatocytes, possess the bipotentiality to differentiate into both hepatocytes and cholangiocytes. Here, we aimed to investigate the optimal conditions for bile duct (BD) induction from rat CLiPs. A two-step induction protocol was used for the differentiation of cholangiocytes. We investigated the effects of passage number, preincubation times, Matrigel, and mouse embryonic fibroblast (MEF) feeder cells on the induction of cholangiocytes. Earlier passages of CLiPs were better for BD induction compared with stable CLiPs. Extending the preincubation time of CLiPs before induction delayed the formation of the BD. Matrigel provided cells with space to form three-dimensional (3D) structures, but the long-term use of Matrigel from the induction step did not benefit the differentiation of CLiPs to cholangiocytes. MEF feeder cells, through the Jag/Notch pathway, affected BD formation and function, as well as gene and protein expression. CLiPs were a good cell source for cholangiocyte differentiation under appropriate conditions and may offer a key vehicle for the study of cholangiopathies in vitro.

Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear.We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis.Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p0.001 and p=0.017, respectively).Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.

Background and Purpose: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a marker of liver fibrosis and hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the diagnostic ability of WFA+-M2BP for occult HCC, which current diagnostic imaging tests fail to detect. Methods: Patients who underwent hepatectomy for liver transplantation (LT) and whose whole liver could be sliced and subjected to histological examination between 2000 and 2018 were eligible for this study (n = 89). WFA+-M2BP levels were measured in samples collected before the LT. Comparison of the postoperative histological test results with the preoperative imaging data grouped the patients into no group (N), detected group (D), increased group (I), and decreased or same group (DS), and the results were compared with the WFA+-M2BP values.Results: Irrespective of underlying hepatic disease conditions, there were 6 patients in the N group, 10 in the D group, 41 in the I group, and 32 in the DS group. The median of the serum WFA+-M2BP level for each group was as follows: N group, 8.05 (1.25–11.9); D group, 11.025 (1.01–18.21); I group, 9.67 (0.29–17.83); and DS group, 9.56 (0.28–19.44) confidence of interval. We found no significant differences between the pairings. Comparison of underlying hepatic diseases revealed that liver cirrhosis due to hepatitis B and C and non-B and -C liver cirrhosis had no significant differences. Conclusion: Serum WFA+-M2BP cannot help diagnose occult HCC that is already undetected using imaging tests in decompensated liver cirrhosis patients requiring LT.

The efficacy of molecular-targeted agents (MTAs) has been demonstrated in recent years. However, the results of multidisciplinary treatment including hepatic resection are still unclear. The present study evaluated the outcomes of MTA treatment for advanced, unresectable hepatocellular carcinoma (HCC), with the goal of achieving liver resection, in our department.Nine patients in whom Lenvatinib had been administered to achieve conversion surgery for unresectable HCC were included in this study. The patient characteristics were as following: median tumor size of 10 cm, vascular invasion in 5 cases, multiple tumors in 2 cases, median treatment duration of 8 weeks, dose reduction due to side effects in 4 patients, and discontinuation of treatment in 1 patient due to tumor growth.The efficacy by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was partial response in 3, sustained disease in 5 and progressive disease in 1, while the liver resection rate was 88%. Four patients (50%) had recurrence after resection, and the median recurrence-free survival was 12.7 months; however, treatment for recurrence was successful and all patients are alive.Lenvatinib may improve the prognosis of HCC with vascular invasion and multiple lesions by achieving radical resection at the appropriate time for patients with tumor shrinkage.

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.

Background: The mechanisms of lymphangiogenesis in the cholestatic liver after partial hepatectomy (PH) remain unclear. We aimed to demonstrate the relationship between lymphangiogenesis and liver regeneration after partial hepatectomy in the cholestatic liver. Methods and Results: C57BL/6 mice were subjected to 70% partial hepatectomy only (PH group, n?=?20) and 70% partial hepatectomy with temporary common bile duct (BD) obstruction by clipping (BD+PH group, n?=?20). Five mice per group were sacrificed at 1, 3, 5, and 7 days after the procedure. The liver function was examined by blood tests, and the liver regeneration rate was assessed by body weight and liver weight. Immunohistochemical staining of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) showed liver lymphangiogenesis. The gene expression of lymphangiogenesis-associated factors (e.g., vascular endothelial growth factor receptor-3 [VEGFR-3]) was examined by a real-time polymerase chain reaction. The liver function in the BD+PH group was worse than that in the PH group on postoperative day 1 (POD1) (aspartate aminotransferase: 6528?±?1641?U/L vs. 2741?±?368?U/L, p?0.05, alanine aminotransferase: 4160?±?1255?U/L vs. 2315?±?357?U/L, total bilirubin: 1.36?±?1.16?mg/dL vs. 0.09?±?0.01?mg/dL), and the liver regeneration rate in the BD+PH group was worse on POD7 (4.57% vs. 5.91%, p?

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.

Background The prognosis of intrahepatic cholangiocarcinoma (ICC) is based on tumor localization; however, the mechanism remains unknown. Therefore, we investigated the biological characteristics of perihilar and peripheral ICC in a mouse model. Methods The model was established by the administration of three oncogenic plasmids harboring myristoylated AKT, mutated human YAP, and pCMV-Sleeping Beauty into the mice. The perihilar and peripheral ICC tumors that developed in the same mouse were assessed for the expression of cell adhesion factors and driver genes with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Results The perihilar ICC tumors were irregularly shaped, whereas the peripheral tumors were mostly circular, similar to the differences found in patients. Alpha-smooth muscle actin was strongly expressed in the perihilar tumors at 10 weeks, and vimentin expression was significantly up-regulated in the perihilar ICC at 14 weeks. Fgfr2 level significantly increased in peripheral ICC at 10 weeks, whereas Idh2 expression was up-regulated in perihilar ICC. Conclusions Despite diffuse injection of oncogenic plasmid, expression of driver genes and oncogenes in ICC tumor cells differs depending on the tumor localization, resulting in changes in epithelial-mesenchymal transition, which may explain the different outcomes of patients with peripheral and perihilar ICC.

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

The systemic cytokine response during surgery has been reported to be stimulated by the molecules released from damaged cells, called damage-associated molecular patterns (DAMPs). The relationship between DAMPs and liver transplantation has not been reported. We aimed to clarify the relationship between the plasma levels of DAMPs and the short-term post-transplant outcomes, including mortality and postoperative multi-organ dysfunction syndrome (MODS). This retrospective cohort study enrolled 61 patients who underwent liver transplantation. Mitochondrial DNA fragments, as mitochondria-derived DAMPs (mtDAMPs), were isolated from frozen plasma obtained at the start and the end of transplantation and were quantified by polymerase chain reaction. The short-term post-transplant outcomes were compared among the groups categorized based on the median value of the intraoperative fluctuation of mtDAMPs levels. The mtDAMPs levels were increased from the start to the end of transplantation in 52 recipients (85.2%, n = 61). Regarding mortality, no significant differences were noted between the high group (n = 30) and the low group (n = 31). The higher plasma levels of mtDAMPs were correlated with the longer duration of postoperative vasopressor support (P < 0.05). Importantly, the rate of MODS on post-operative day 1 was significantly higher in the high group (high vs. low group: 21 patients [70%] vs. 11 patients [35.1%], P < 0.01). In conclusion, mtDAMPs were increased in plasma during liver transplantation in most recipients. This elevation was not associated with mortality, but associated with the post-transplant recovery. Measuring plasma mtDAMPs may be helpful for predicting posttransplant recovery among liver-transplant recipients.

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

A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.

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.

Acoustic radiation force impulse (ARFI) elastography is widely used for evaluating liver fibrosis. Here we evaluated the efficacy of ARFI elastography for estimating graft quality and clinical outcomes in living donor liver transplant (LDLT).We retrospectively evaluated the cases of 87 LDLT donors who preoperatively underwent ARFI elastography at Nagasaki University Hospital between August 2010 and June 2016. We analyzed whether the velocity of shear wave (Vs) obtained by ARFI elastography affected the regeneration rate of each donor's remnant liver and the 1-year survival rate of the recipients.There were no significant correlations between Vs value and the donors' age. Only 1 donor (1.1%) showed significant fibrosis, F2 (portal fibrosis with few septa) in zero-biopsy. The 7 donors (8.0%), including 1 case, showed a high Vs value ( 1.33) that was equal to F2, although there was no abnormal pathologic finding except in 1 case. In those cases, the regeneration rate of the remnant liver after hepatectomy was significantly lower compared to other cases. The 1-year survival rate of the recipients paired with the high-Vs donors was also significantly poorer than that of the other cases (high-Vs: 57.1%, others: 84.2%, P = .04).ARFI elastography might be an effective examination for the preoperative evaluation of the graft quality in LDLT.

Portal vein thrombosis following liver transplantation is generally managed by endovascular treatment. Although several techniques are available for portal venous access, trans-splenic access is of interest because it avoids damage to the liver graft. However, the spleen cannot be punctured to access the portal vein after splenectomy. We herein report a case of portal vein thrombosis following living donor liver transplantation with simultaneous splenectomy successfully treated by percutaneous intervention with direct puncture of the retropancreatic splenic vein. The splenic vein was punctured under computed tomography guidance in the prone position. Portal venography revealed a contrast defect due to a thrombus in the extrahepatic to intrahepatic portal vein. The portal vein was reopened after thrombectomy, and the portal vein thrombosis did not recur for 2 y. The technique and advantages of our approach are described., Transplantation Direct, 9 (1), art. no. e1425; 2022

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 present a case of advanced gastric cancer with paraaortic lymph node metastasis successfully treated by conversion therapy. The patient was a 71‒year‒old male. Because of paraaortic lymph node metastasis, we initiated intensive chemotherapy with S‒1, oxaliplatin, and trastuzumab. After 6 courses, CT examination revealed that the size of the primary tumor decreased, suggesting a complete response(CR). Furthermore, the metastatic lymph nodes decreased in both number and size, suggesting a partial response(PR). We continued chemotherapy, changing to S‒1 and trastuzumab only because of Grade 3 neutropenia, and conducted continuous infusion chemotherapy. After 5 courses, we performed an upper gastrointestinal endoscopy. The primary tumor recurred, suggesting a progressive disease(PD), while metastasis to the paraaortic lymph nodes disappeared. We decided that a curative resection was possible and performed distal gastrectomy with D2 and paraaortic lymph node dissection. The postoperative courses were uneventful, and the patient was discharged from the hospital 12 days postoperation. The patient is well without any recurrence of cancer at 1 year 3 months postoperation. Conversion therapy may offer the possibility of prolonged survival for patients with gastric cancer previously considered unresectable.

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.

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

Summary: Background: The aim of this study was to investigate the impact of Daikenchuto (DKT) on early postoperative outcomes after living donor liver transplantation (LDLT), focusing on the prevention of abdominal distension and bacterial translocation. Methods: Adult LDLT recipients were prospectively divided into 2 groups, who were administered DKT (n = 20, group A) or not (n = 20, group B). The area of bowel gas defined as gas volume score (GVS) 7 days after LDLT was calculated. Postoperative liver function tests, the development of bacterial, viral, and fungal infections, and GVS after LDLT were reviewed. Results: There were no significant differences in liver function tests and ammonia level after LDLT. Also, the rates of infection and the result of culture study were not different between groups. The median GVS 7 days after LDLT was not significantly different between groups A (0.26 (range, 0.12–0.58)) and B (0.23 (range, 0.15–0.42)). Conclusions: No positive impact was observed for 14-day DKT administration after LDLT, in terms of preventing infection or abdominal distension. Keywords: Living donor, Liver transplantation, Daikenchuto, Herbal drug, Bowel gas

This study presents the practical results concerning model-based development educational practices implemented by Hiroshima University and Mazda Motor Corporation, an automobile manufacturer, and the consequent educational effects. Importance of model-based development is increasing in industrial world. Model-based development is performed according to a development process called the ”V-type development process (V-process).” However, several professional engineers involved in automobile development have insufficient experience in conducting model-based development. In this study, the authors propose a program that allows these professional engineers to learn the V-process using a motor control system via a hands-on approach. The program is implemented to target 159 professional engineers belonging to Mazda Motor Corporation. From the questionnaire surveys taken by the learners, it is revealed that the V-process exercises considerably contribute to the self-efficacy of the learners for operational performance using model-based development.

Objective: For successful biliary anastomosis in living donor liver transplantation (LDLT), the efficacy of a biliary splint at the anastomosis remains controversial. In the case of biliary anastomotic stricture (BAS), endoscopic intervention is mostly performed as the initial treatment. In this study, we evaluated the efficacy of endoscopic treatment for BAS in patients with placement of splints. Methods: A retrospective study was conducted with 148 adult patients who underwent LDLT with duct-to-duct biliary anastomosis from 2005 to 2015. A biliary splint was placed in all cases; the splint was removed 3 months after the LDLT. Patients who postoperatively underwent endoscopic treatment for BAS were divided into successful and failed groups. Results: A total of 24 patients (16.2%) underwent endoscopic treatment postoperatively. The successful group included 14 patients (63.6%) and the failed group included 8 (36.4%). Comparison between the 2 groups in terms of demographic, pretransplant, intraoperative, and posttransplant data did not show any significant differences. Two patients developed BAS within 3 months after LDLT. In these 2 patients, the splint was dislocated, and endoscopic intervention was not successful. Twenty patients developed BAS later than 3 months after LDLT. In contrast to the success rate of endoscopic intervention of 73.3% in patients without splint dislocation (n = 15), it was 60% in the patient with dislocation of the splint (n = 5). Conclusion: The prevention of early biliary stricture by placing a splint may lead to an improved success rate of endoscopic intervention, since endoscopic intervention was difficult in the cases of early biliary stricture within 3 months.