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Abstract The liver requires careful handling intra‐operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like “robotic surgery in liver transplantation,” “robotic hepatectomy for hilar cholangiocarcinoma,” “robotic vascular reconstruction following hepatectomy,” “robotic repeat hepatectomy,” and “prospective trials in robotic hepatectomy.” To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5‐year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting‐edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research.

Abstract Background Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine. Methods In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs). hCLiPs were induced in mature cryo-hepatocytes using a small-molecule cocktail of TGF-β inhibitor (A-83-01, A), GSK3 inhibitor (CHIR99021, C), and 10% FBS (FAC). HBOs were then formed by seeding hCLiPs into ultralow attachment plates and culturing them with a combination of small molecules of Rock-inhibitor (Y-27632) and AC (YAC). Results These HBOs exhibited bile canaliculi of MHs connected to BD structures, mimicking bile secretion and transportation functions of the liver. The organoids showed gene expression patterns consistent with both MHs and BD structures, and functional assays confirmed their ability to transport the bile analogs of rhodamine-123 and CLF. Functional patient-specific HBOs were also successfully created from hCLiPs sourced from cirrhotic liver tissues. Conclusions This study demonstrated the potential of human HBOs as an efficient model for studying hepatobiliary diseases, drug discovery, and personalized medicine.

Abstract Background Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt‐PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt‐PDAC. Patients and method This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt‐PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt‐PDAC prognosis were investigated. Results There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt‐PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence‐free survival (HR = 2.01, 95% CI = 1.33–3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence‐free survival. Conclusions LN dissection along the hepatic artery for Pt‐PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short‐term outcomes and preservation of pancreatic function is required.

Background. Patients undergoing liver transplantation are in a state of coagulopathy before surgery because of liver failure. Intraoperative hemorrhage, massive transfusions, and post–reperfusion syndrome further contribute to coagulopathy, acidosis, and hypothermia. In such situations, temporary cessation of surgery with open abdominal management and resuscitation in the intensive care unit (ICU), which is commonly used as a damage control strategy in trauma care, may be effective. We assessed the outcomes of open abdominal management in liver transplantation and the corresponding complication rates. Methods. We retrospectively reviewed the outcomes of patients undergoing open abdominal management among 250 consecutive liver transplantation cases performed at our institution from 2009 to 2022. Results. Open abdominal management was indicated in 16 patients. The open abdomen management group had higher Model for End-stage Liver Disease scores (24 versus 16, P

Abstract Aim After pancreaticoduodenectomy, 20–40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin‐like phospholipase domain‐containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results Forty‐three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real‐time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver‐to‐spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis‐4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Abstract Background Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. Case report The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. Conclusions To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, and the integration between the BD and hepatocytes is the basis of the liver function. However, the lack of a source of cholangiocytes limits in vitro research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) in vitro using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs.Methods: In this study, we formed functional BDs from hCLiPs using hepatocyte growth factor and extracellular matrix. BDs expressed the typical biliary markers CK-7, GGT1, CFTR and EpCAM and were able to transport the bile-like substance rhodamine 123 into the lumen. The established three-dimensional BDs were cocultured with hMHs. These cells were able to bind to the BDs, and the bile acid analog CLF was transported from the culture medium through the hMHs and accumulated in the lumen of the BDs. The BDs generated from the hCLiPs showed a BD function and a physiological system (e.g., the transport of bile within the liver) when they were connected to the hMHs.Conclusion: We present a novel in vitro three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.

Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.

Abstract Background and Aim Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute. Methods We compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules

BackgroundDaikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model.MethodsIntraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15.ResultsThe DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-β1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption.ConclusionDKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

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.

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.

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

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.

Abstract Background Congenital absence of portal vein (CAPV) is a rare structural anomaly in which the portal vein (PV) blood that normally flow into the liver directly drains into the systemic venous system through other collateral circulation. Congenital portal vein shunts (CPSs) is classified into types I and II according to the absence or presence of the intrahepatic portal vein, respectively. The CPS type I is also known as CAPV. The liver transplantation may be the only treatment option for CAPV. The key point of liver transplantation for CAPV is the reconstruction of the PV. Case presentation A 29-year-old man was diagnosed with CAPV with splenomegaly and gastroesophageal varix when being treated for pancytopenia and liver dysfunction. A living donor liver transplantation was performed for him using the right lobe which had been donated by his mother. The PV was reconstructed using his own great saphenous vein (GSV) as a graft vein. The end of the GSV graft was anastomosed to the inferior mesenteric vein while the other end was anastomosed to the vein graft of the right hepatic vein from the explanted liver. Conclusion Using the patient’s own GSV for PV reconstruction during living donor transplantation in the patient with CAPV seems to be an effective method.

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.

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.

Abstract 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.

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.

Abstract 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.

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

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. Keywords: Segmental arterial mediolysis, Stenting, Aneurysm

ABSTRACT 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: 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 after qualification as transplantation program. Patients and methods: Between September 2017 and July 2018, we performed 3 SPK in type 1 diabetic patients with end-stage renal disease. All grafts were procured from brain-dead marginal donors according Pittsburg criteria. Results: The recipients were 2 men and 1 woman with a mean age of 43 ± 5.4 years. Mean time from DM diagnosis and time on dialysis were 25.7 ± 3.9 years and 19.7 ± 9.1 months. The mean age and HbA1C value of donor were 56.7 ± 0.5 years and 5.67 ± 0.05%. The pancreatic grafts were transplanted intraperitoneally in the right iliac fossa. Two patients required a relaparotomy due to arterial anastomotic hemorrhage and two patients developed acute cellular rejection. With a median follow-up of 13 (6–15) months, patient's and graft's survival rate were 100%. All patients showed HbA1C within normal range, but oral glucose tolerance test showed 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 the results reported in literature. Despite the limited availability of donors and the use of grafts from marginal donors, 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. Keywords: Simultaneous pancreas-kidney transplantation, Initial experience, Postoperative bleeding, Acute cellular rejection

PurposePancreatic cancer is the 4th most common cause of cancer death in Japan and exhibits a 5-year overall survival rate of approximately 7%. The accurate diagnosis of pancreatic cancer is important for determining the optimal management strategy. Fludeoxyglucose-positron emission tomography (FDG PET) integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for detecting and evaluating various cancers, and it is used for staging, detecting local recurrence and distant metastasis, measuring therapeutic effects, and predicting prognosis in pancreatic cancer patients. Lately, FDG PET/CT-derived parameters, such as standardized uptake values (SUV), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG), have been suggested as prognostic factors for various types of cancer, including pancreatic cancer. However, there is no consensus regarding the best parameters for evaluating patient prognosis, operability, etc. The purpose of this study was to examine the differences between operable and non-operable pancreatic cancer using FDG PET/CT-derived parameters, and to investigate whether volumetric parameters (TLG and the MTV) are superior to SUV-based parameters for predicting infiltration status/determining operability.Materials and methodsWe conducted a retrospective study of the cases of 48 patients with clinically proven pancreatic adenocarcinoma, who underwent FDG PET/CT imaging before treatment. In the operable group, the surgical specimens were subjected to histopathological examinations, and the cases were separated into those exhibiting less and greater infiltration. SUVmax, SUVpeak, the tumor background ratio (TBR), TLG, and the MTV were compared between these groups as well as between the operable and non-operable groups.ResultsVenous infiltration showed significant associations with several metabolic parameters (SUVmax, SUVpeak, and the TBR). However, it did not display any significant associations with volumetric parameters, such as TLG or the MTV. None of the FDG PET/CT-derived parameters exhibited significant associations with lymphatic or neural infiltration. Significant differences in volumetric parameters, such as the MTV and TLG, were detected between the operable and non-operable subgroups.ConclusionsMetabolic 18F-FDG PET/CT-derived parameters, such as SUVmax, SUVpeak, and the TBR, are useful for predicting venous infiltration status in patients with operable pancreatic adenocarcinoma.

Chemically induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. Three-dimensional (3D) structures generated from liver progenitor cells possess wide applications in cell transplantation, disease model, and drug testing. Here, we report on the spontaneous formation of 3D cystic structures comprising maturing rat CLiPs on gelatin-coated dishes. Our 3D cysts contained Alb+/+CK19+/− and Ck19+/+Alb+/− cells. These cell types gradually diverged into specialized mature cells, as demonstrated by the expression of mature biliary markers (Cftr, Ae2, and Aqp1) and hepatic markers (Alb and Mrp2). The 3D cysts also expressed functional multidrug resistance protein 1 (Mdr1), as indicated by epithelial efflux of rhodamine. Furthermore, we observed bile canaliculi functions between hepatocytes and cholyl-lysyl-fluorescein extrusions, indicating that the functional characteristics of 3D cysts and active bile salt export pump (Bsep) transporters were intact. Thus, our study revealed a natural characteristic of rat CLiPs to spontaneously form 3D cystic structures accompanied with cell maturation in vitro, offering a platform for studies of liver development and drug screening.

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.

Background. Given the expected increase in the number of elderly recipients, details regarding how clinical factors influence the outcome in living donor liver transplantation (LDLT) for the elderly remain unclear. We examined the survival outcomes according to the results of donor age-based and graft volume–based analyses and assessed the impact of prognostic factors on the survival after LDLT for elderly recipients. Methods. The 198 adult recipients were classified into 2 groups: an elderly group (n = 70, E group; ≥ 60 years of age) and a younger group (n = 128, Y group;

In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 ± 9.8%, 87.4 ± 5.8%, and 88.6 ± 4.5%, and survival rates were 60.3 ± 6.8%, 65.3 ± 3.0%, and 75.8 ± 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 ± 1.6, 9.4 ± 3.8, and 23.5 ± 12.4 μIU/islet, and interleukin-6 (IL-6) secretions were 3.0 ± 0.7, 5.1 ± 1.2, and 7.3 ± 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix.

Single-incision laparoscopic cholecystectomy (SILC) has rapidly spread throughout the world because of its low invasiveness and because it is a scarless procedure. Various surgical methods of performing SILC are present in each institute; however, it is necessary to develop a standardized procedure that we can perform safely, such as the conventional 4-port laparoscopic cholecystectomy (LC). The SILC experiment in our institute was started by use of the commercial SILS Port and changed from a 3-port method via an umbilicus to a 2-port method to improve some problems. Although none of the conversions to conventional 4-port LC and also none of the complications such as bile duct injury occurred in each method, the 2-port method functioned best and was also economical. However, it is most important to adopt strict criteria and select the patients suitable for SILC to demonstrate SILC safety same as 4-port LC.

Objective: Unusual or unexpected effect of treatment Background: Minimally invasive pancreatectomy has become the standard practice for the management of benign and malignant pancreatic tumors. Techniques such as robotic and laparoscopic approaches are known to reduce morbidity by offering benefits such as less blood loss, reduced pain, shorter hospital stays, and quicker recovery times. The indication for repeated minimally invasive pancreatectomy for recurrent or de novo pancreatic neoplasm after primary pancreatic surgery remains debated. Case Report: A 50-year-old woman was admitted to our hospital with a diagnosis of an intraductal papillary mucinous neoplasm in the pancreatic head. In 2010, she underwent laparoscopic single-branch resection for a branch-type tumor in the pancreatic uncinate process. During a 5-year follow-up, a de novo intraductal papillary mucinous neoplasm was detected, showing gradual growth and the presence of a mural nodule over the next 7 years. The patient’s CEA level was elevated to 7.0 ng/mL. Considering the tumor’s progression and the appearance of a mural nodule, we recommended a robot-assisted Whipple procedure. The operation began with laparoscopic adhesiolysis. After detachment of the adhesions and remobilization of the duodenum using the Kocher maneuver, the operation continued with the Da Vinci surgical system. The postoperative period was uneventful, and the patient was discharged on postoperative day 20. Pathological examination revealed intraductal papillary mucinous carcinoma in situ with negative resection margins. Conclusions: This case verifies the safety and feasibility of performing a robotic Whipple procedure for a newly diagnosed pancreatic neoplasm in patients who have previously undergone minimally invasive pancreatic surgery. [ABSTRACT FROM AUTHOR]

Objective: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. Background: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. Methods: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n =6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. Results: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥ 0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (> 60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. Conclusion: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥ 5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution. [ABSTRACT FROM AUTHOR]