A Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell-Cell Interaction and Angiogenesis.

Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell-cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the in vivo assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell-cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.

A thioacetamide-induced liver fibrosis model for pre-clinical studies in microminipig.

Drug-induced liver fibrosis models are used in normal and immunosuppressed small animals for transplantation and regenerative medicine to improve liver fibrosis. Although large animal models are needed for pre-clinical studies, they are yet to be established owing to drug sensitivity in animal species and difficulty in setting doses. In this study, we evaluated liver fibrosis by administering thioacetamide (TA) to normal microminipig and thymectomized microminipig; 3 times for 1 week (total duration: 8 weeks). The pigs treated with TA showed elevated blood cytokine levels and a continuous liver injury at 8 weeks. RNA-seq of the liver showed increased expression of fibrosis-related genes after TA treatment. Histopathological examination showed degenerative necrosis of hepatocytes around the central vein, and revealed fibrogenesis and hepatocyte proliferation. TA treatment caused CD3-positive T cells and macrophages scattered within the hepatic lobule to congregate near the center of the lobule and increased αSMA-positive cells. Thymectomized pigs showed liver fibrosis similar to that of normal pigs, although the clinical signs tended to be milder. This model is similar to pathogenesis of liver fibrosis reported in other animal models. Therefore, it is expected to contribute to research as a drug discovery and pre-clinical transplantation models.

Risk Assessment of Liver Transplantation After Kasai Portoenterostomy in Children and Adults.

INTRODUCTION: Reports of liver transplantation (LT) after Kasai portoenterostomy (KPE) in adult patients with biliary atresia are scarce. The aim of this study was to evaluate the outcomes and investigate the risk factors of LT after KPE in both pediatric and adult patients. METHODS: We retrospectively reviewed a prospective database of patients with biliary atresia who underwent LT after KPE. Eighty-nine consecutive patients were included, and risk factors for in-hospital mortality after LT were assessed. RESULTS: The median age of the patients was 2 y (range, 0-45 y). Forty-six patients (51.7%) had a history of upper abdominal surgery after KPE. The in-hospital mortality rate was 5.6% (5 patients). Of these, 80% of patients with mortality were aged ≥17 y, and all patients with mortality had a history of two or more upper abdominal surgeries. In the univariate and receiver operating characteristic curve analyses, age ≥17 y and the number of previous upper abdominal surgeries ≥2 were identified as possible risk factors. CONCLUSIONS: Our study suggests that older age and multiple previous upper abdominal surgeries are important risk factors for mortality after LT following KPE. We believe that these findings will serve as indications for safe LT in future patients.

Surgery for colloid carcinoma of the pancreas with portal vein tumor thrombus: a case report.

BACKGROUND: The portal vein is occasionally invaded by advanced malignant tumors in the pancreatic head region. However, pancreatic cancer rarely has portal vein tumor thrombi. We report a case of pancreatic cancer with a massive portal vein tumor thrombus undergoing pancreatoduodenectomy with combined resection of the portal vein. CASE PRESENTATION: A 71-year-old man visited a clinic with complaints of abdominal discomfort and vomiting. Gastroscopy showed a massive tumor in the duodenum. He was referred to our hospital for further examinations and treatment. The CT showed a low-density tumor with a maximum diameter of 10 cm located on the pancreas head. A tumor widely invaded the duodenum and had a 6-cm portal vein tumor thrombus. MRCP did not show obvious stenosis of the pancreatic duct due to tumor invasion. There were no findings suggesting distant metastases. Biopsy of the duodenum revealed adenocarcinoma. He was diagnosed with primary pancreatic cancer or duodenal cancer with portal vein tumor thrombus and underwent pancreatoduodectomy with resection and reconstruction of the portal vein. He suffered no postoperative complications and was discharged 2 months after surgery. The final histopathological diagnosis was pancreatic colloid carcinoma. He received adjuvant chemotherapy, but died 16 months after surgery. CONCLUSIONS: Colloid carcinoma of the pancreas is rare, and pancreatic carcinoma seldom forms a portal vein tumor thrombus. We experienced a very rare case of pancreatic colloid carcinoma with portal vein tumor thrombus and performed radical resection of the pancreas and portal vein.

Is human life worth peanuts? Risk attitude changes in accordance with varying stakes.

Risk aversion is well-known as a general and robust characteristic of people's decision making: people are less likely to gamble when they are unsure if they will obtain the expected value of the bet made. The "peanuts effect" is, however, an exception to this general rule. The "peanuts effect," which states that people are more willing to gamble when playing for "peanuts" (a small outcome), has been stably observed in the context of a small monetary stake. We conducted two types of experiments to verify whether the peanuts effect still occurred when the type of stakes changed. We had two main findings. On the one hand, people tended to gamble more for a qualitatively smaller value when the stake was material in nature, meaning that the "peanuts effect" occurred with a qualitatively low stake. On the other hand, people were willing to take a risk for a qualitatively larger value when the stake was a human life: this is the opposite phenomenon of the "peanuts effect."

How can group experience influence the cue priority? A re-examination of the ambiguity-ambivalence hypothesis.

Since the discovery of the "framing effect" by Kahneman and Tversky, the sensitivity of the "framing effect" - its appearance and in some cases its disappearance - has long been an object of study. However there is little agreement as to the reasons for this sensitivity. The "ambiguity-ambivalence hypothesis" (Wang, 2008) aims to systematically explain the sensitivity of this effect by paying particular attention to people's cue priority: it states that the framing effect occurs when verbal framing is used to compensate for the absence of higher prioritized decision cues. The main purpose of our study is to examine and develop this hypothesis by examining cue priority given differences in people's "group experience." The main result is that the framing effect is absent when the choice problem is presented in a group context that reflects the actual size of the group that the participant has had experience with. Thus, in order to understand the choices that people make in life and death decisions, it is important to incorporate the decision maker's group experience explicitly into the ambiguity-ambivalence hypothesis.