Repeated Minimally Invasive Pancreatectomy for Intraductal Papillary Mucinous Neoplasm in the Remnant Pancreas: A Case Report.

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.

Efficacy of chemically induced human hepatic progenitor cells from diseased liver against nonalcoholic steatohepatitis model.

BACKGROUND: Numerous chemical reprogramming techniques have been reported, rendering them applicable to regenerative medicine research. The aim of our study was to evaluate the therapeutic potential of human CLiP derived from clinical specimens transplanted into a nonalcoholic steatohepatitis (NASH) mouse model of liver fibrosis. METHODS: We successfully generated chemically induced liver progenitor (CLiP), which exhibited progenitor-like characteristics, through stimulation with low-molecular-weight compounds. We elucidated their cell differentiation ability and therapeutic effects. However, the therapeutic efficacy of human CLiP generated from clinical samples on liver fibrosis, such as liver cirrhosis, remains unproven. RESULTS: Following a 4 week period, transplanted human CLiP in the NASH model differentiated into mature hepatocytes and demonstrated suppressive effects on liver injury markers (i.e., aspartate transaminase and alanine transaminase). Although genes related to inflammation and fat deposition did not change in the human CLiP transplantation group, liver fibrosis-related factors (Acta2 and Col1A1) showed suppressive effects on gene expression following transplantation, with approximately a 60% reduction in collagen fibers. Importantly, human CLiP could be efficiently induced from hepatocytes isolated from the cirrhotic liver, underscoring the feasibility of using autologous hepatocytes to produce human CLiP. CONCLUSION: Our findings demonstrate the effectiveness of human CLiP transplantation as a viable cellular therapy for liver fibrosis, including NASH liver. These results hold promise for the development of liver antifibrosis therapy utilizing human CLiP within the field of liver regenerative medicine.

Minimally invasive pancreaticoduodenectomy for circumportal pancreas: literature review and report of two type IIIA cases.

BACKGROUND: Circumportal pancreas is a rare morphological variant with clinical significance due to the high risk of postoperative pancreatic fistula in patients undergoing pancreaticoduodenectomy. Type IIIA (suprasplenic anteportal) is the most common type of circumportal pancreas. We present two cases of type IIIA treated with minimally invasive pancreaticoduodenectomy, and review the literature on patients with circumportal pancreas who underwent pancreatic surgery. CASE PRESENTATION: Case 1: Laparoscopic Pancreaticoduodenectomy for Non-functioning Pancreatic Neuroendocrine Neoplasm with Circumportal Pancreas. A 69-year-old female with no prior medical history presented with a pancreatic head mass detected during routine ultrasound. CT revealed a 20 mm hypervascular tumor in pancreas head and a suprasplenic circumportal pancreas with an anteportal duct. The main pancreatic duct (MPD) was not in the parenchyma on the dorsal side of the portal vein (PV). Laparoscopic pancreaticoduodenectomy was performed. The anteportal side was resected with an ultrasonic device, and the retroportal side with a mesh-reinforced stapler. Pancreaticojejunostomy was performed without complications. Case 2: Robot-assisted Pancreaticoduodenectomy for Pancreatic Head Cancer and Non-functioning Pancreatic Neuroendocrine Neoplasm in the pancreatic tail with Circumportal Pancreas. A 72-year-old male with no prior medical history presented with a dilated main pancreatic duct on ultrasound. Diagnosed with pancreatic head cancer (Stage IIA), he underwent neoadjuvant chemotherapy. Contrast-enhanced CT revealed pancreatic cancer in the head and a tumor in the tail with unknown pathology. Robot-assisted pancreaticoduodenectomy was performed, and pancreatectomy on the left side of the tail tumor was planned. Intraoperative findings revealed a circumportal pancreas with the MPD not running through the dorsal parenchyma. After resected the parenchyma on the left side of the tail tumor, parenchyma on the dorsal side of the PV was dissected using SynchroSeal®. Pancreaticojejunostomy was performed without complications. The postoperative course was uneventful. CONCLUSIONS: The optimal location and method of pancreatic resection should be selected according to the type of circumportal pancreas and the location of the lesion to be resected to minimize the risk of pancreatic fistula. Minimally invasive surgery for circumportal pancreas remains challenging even for surgical teams with sufficient experience and skills, and careful consideration are necessary for its application.

DCLK1 Expression and its Functional Significance in Intrahepatic Cholangiocarcinoma and Bil-IN Stage.

BACKGROUND/AIM: Although several studies in some neoplasms have reported correlation between the expression levels of Doublecortin-like kinase1(DCLK1) and carcinogenesis, its role in cholangiocarcinoma remains unknown. MATERIALS AND METHODS: DCLK1 expression in normal epithelium (NE), biliary intraepithelial neoplasia (BilIN)1∼3, and intrahepatic cholangiocarcinoma (ICC) were investigated immuno-histochemically. The molecular effects of DCLK1 were investigated by gene silencing using RNAi [DCLK1-tagrgeting (siDCLK1)]. The human ICC cell lines HuCCT1 and HuH28 were transfected with these siRNAs, and used for assays in the presence or absence of DCLK1 inhibitors. RESULTS: The positive ratio of DCLK1 expression in ICC was higher than that in NE, and equally distributed among BilIN1∼3 (NE: BilIN1: BilIN2: BilIN3: ICC=62%: 91%: 97%: 100%: 95%, p<0.05). In the wound healing assay, the migration of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the cell invasion assay, the invasion of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the presence of the DCLK1 inhibitor, cell proliferative capacity at 24 hours was decreased in a concentration-dependent manner. CONCLUSION: DCLK1 was highly expressed in the early stage of ICC carcinogenesis. Human ICC cell growth was suppressed in vitro by siRNA silencing of DCLK1 or after treatment with the DCLK1 inhibitor, indicating DCLK1 may be molecular target for ICC therapy.

Improvement in aged liver regeneration using cell transplantation with chemically induced liver progenitors.

BACKGROUND: A decrease in the regenerative capacity of age-damaged liver tissue has been reported. Liver progenitor cells may play an important role in the regeneration of injured livers. In the present study we aimed to investigate improvements in the regenerative capacity of age-damaged livers using chemically induced liver progenitors (CLiPs) derived from mature hepatocytes. METHODS: Old (>90 weeks) and young (<20 weeks) mice underwent 70% hepatectomy, with or without trans-splenic CLiP administration. The residual liver/bodyweight (LW/BW) ratio was measured on postoperative days 1 and 7, and changes in liver regeneration and histology were evaluated. RESULTS: At 7 days post-hepatectomy, LW/BW ratios were significantly better in CLiP-treated old mice than in untreated old mice (p = .02). By contrast, no effect of CLiP transplantation was observed in young mice (p = .62). Immunofluorescence staining of liver tissue after CLiP administration showed an increase in Ki67-positive cells (p < .01). Flow cytometry analysis of green fluorescent protein-labeled CLiPs indicated that transplanted CLiPs differentiated into mature hepatocytes and were present in the recipient liver. CONCLUSIONS: CLiP transplantation appears to ameliorate the age-related decline in liver regeneration in mice.

Analysis of the Clinical Course in a Population of Patients with Biliary Tract Cancer Diagnosed as Unresectable After Portal Vein Embolization: A Case Series.

Portal vein embolization (PVE) is recommended as a preoperative procedure for patients with biliary tract cancer scheduled to undergo hepatic resection of more than 50%-60% of the liver. However, details and/or information regarding the follow-up of unresectable cases are often lacking, and the clinical course of unresectable cases is not well analyzed and reported. This study aimed to clarify the clinical prognosis of patients with unresectable biliary tract cancer after PVE. We retrospectively analyzed the clinical backgrounds of patients with biliary tract cancer who underwent PVE without subsequent resection between January 2011 and October 2022. Of the 21 patients with biliary tract cancer who underwent PVE during the study period, eight (38%) cases were unsuitable for resection after PVE for the following reasons: intraoperatively detected dissemination (n=2), para-aortic lymph node metastasis (n=1), liver metastasis (n=1), decreased liver function (n=2), development of liver metastasis while waiting (n=1), and insufficient residual liver volume (n=1). All patients received subsequent chemotherapy, including gemcitabine plus S-1 therapy in three cases, gemcitabine plus cisplatin plus S-1 in three cases, and gemcitabine plus cisplatin or S-1+cisplatin in one case each. As there is currently no curative treatment for biliary tract cancer other than surgery, multidisciplinary management and treatment of patient factors, including tumor factors and liver function, are essential to reducing the number of unresectable cases after PVE.

Outcomes of living donor liver transplant recipients receiving grafts with the graft-to-recipient weight ratio less than 0.6%: A matched pair analysis.

We sometimes experience living donor liver transplantation (LDLT) involving very small grafts with graft-to-recipient weight ratio (GRWR) < 0.6% when the actual graft size is smaller than predicted. The outcomes in this situation have not been fully investigated. The present study aimed to determine the graft outcomes of LDLT with GRWR < 0.6%. We retrospectively reviewed 280 cases of adult LDLT performed at our institution between January 2000 and March 2021. In our institution, the lower limit for graft volume/standard liver volume ratio was 30%. The patients were divided into 2 groups according to the cutoff value of 0.6% for actual GRWR. Graft survival and surgical outcomes, including small-for-size syndrome (SFSS), were compared between the groups using propensity score matching analysis. Risk factors associated with SFSS in recipients with GRWR < 0.6% were also evaluated. Fifty-nine patients received grafts with GRWR < 0.6%. After propensity score matching, similar graft survival rates were observed for GRWR < 0.6% (n = 53) and GRWR ≥ 0.6% (n = 53) ( p = 0.98). However, patients with GRWR < 0.6% had a significantly worse 3-month graft survival rate (86.8% vs. 98.1%, p = 0.03) and higher incidence of SFSS ( p < 0.001) than patients with GRWR ≥0.6%. On multivariate analysis, Model for End-Stage Liver Disease score and donor age were associated with SFSS in patients with GRWR < 0.6%. The same factors were also associated with graft survival. In conclusion, although similar overall graft survival rates were observed for LDLT with GRWR < 0.6% and GRWR ≥ 0.6%, GRWR < 0.6% was associated with an increased risk of SFSS. Appropriate donor and recipient selection is important for successful LDLT with very small grafts.

Serum wisteria floribunda agglutinin-positive human Mac-2 binding protein is unsuitable as a diagnostic marker of occult hepatocellular carcinoma in end-stage liver cirrhosis.

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 2010 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 histologically no group (N), histologically detected group (D), histologically increased group (I), and histologically decreased or same group (DS), and the results were compared with the WFA+-M2BP values. In addition, comparisons were made between each data with and without HCC, including occult HCC, and total tumor diameter. 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. AFP levels, on the other hand, had significant relationships in comparison between the presence or absence of histological HCC, in correlation between total tumor diameter, and in the ROC analysis for the diagnosis of HCC including occult HCC. CONCLUSION: Serum WFA+-M2BP cannot help diagnose occult HCC that is already undetected using imaging tests in decompensated liver cirrhosis patients requiring LT.

Evolution of Liver Transplantation Over the Last 2 Decades Based on a Single-Center Experience of 300 Cases.

BACKGROUND Over the past 2 decades, there have been many medical advances in the field of liver transplantation. We conducted this study to evaluate the changes in liver transplantation over the last 2 decades. MATERIAL AND METHODS Three hundred cases of liver transplantation encountered between 1997 and 2019 in Nagasaki University Hospital were divided into 3 groups: Era 1 (cases no. 1-100), Era 2 (cases no. 101-200), and Era 3 (cases no. 201-300). Several items were compared among the groups. RESULTS There were no cases of deceased-donor liver transplantation in Era 1, 1 case in Era 2, and 12 cases in Era 3. The proportion of virus-related disease was significantly lower in Era 3 compared to other eras. In contrast, the proportion of alcoholic liver cirrhosis was significantly higher in Era 3 (27%) than Era 1 (7%) and Era 2 (10%) (P<0.01). In Era 1, the right lobe was selected most frequently, but in Eras 2 and 3, the left lobe was more frequently selected. CONCLUSIONS The evolution of the treatment and the transplant system in Japan is clearly reflected in the indications and types of donors for liver transplantation, even at a single center in Japan.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report.

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.

Angioplasty of the inferior vena cava with a bovine pericardial patch by the modified open-chest dorsal approach for Budd-Chiari syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Surgical treatment of Budd-Chiari syndrome (BCS) includes endovenectomy followed by angioplasty of the inferior vena cava (IVC). Herein, we report a case of surgery using an open-chest approach in a patient with BCS. We modified the technique reported by Kuniyoshi et al. CASE PRESENTATION: A 45-year-old male, was diagnosed with BCS and referred to our hospital. We used an open-chest approach to remove stenosis in the IVC and angioplasty with a bovine pericardial patch. Endovenectomy and angioplasty were performed by clamping the stenosis above and below it with Pringle's clamping under extracorporeal circulation. The patient is currently undergoing outpatient follow-up 14 months after the surgery, and his liver function and blood test results were normal, with no symptoms. CLINICAL DISCUSSION: The main advantage of this technique is that the liver is not mobilized from the diaphragm, which allows for the preservation of collateral blood flow between the diaphragm and liver, reducing the amount of intraoperative blood loss and damage to the liver parenchyma due to intraoperative congestion. In addition, no mobilization of the liver from the diaphragm will prevent future surgical difficulties due to adhesions during total hepatectomy when liver transplantation becomes necessary. CONCLUSION: The techniques described in this article include procedures that cardiovascular surgeons usually perform such as thoracotomy, pericardiotomy, and extracorporeal circulation. Collaborative work by hepatobiliary surgeons and cardiovascular surgeons can achieve successful outcomes with this procedure in patients with BCS.

Feasibility of Organ Transportation by a Drone: An Experimental Study Using a Rat Model.

BACKGROUND: Recently, the successful delivery of organs for transplantation using drones was reported. We investigated the influence of transportation by drones on the quality of liver grafts using a rat model. METHODS: Livers of 12 rats (8 and 32 weeks old) were divided into 2 groups of six. Livers were split into 2 parts and allocated to the drone or control groups (both n = 12). The drone experiment was conducted between islands in Nagasaki Prefecture, Japan. The distance between the islands was 12 km. Livers of the drone group were transported by a multicopter at a speed of 30 km-40 km/h over 60 m above sea level. Transported liver quality was analyzed by histology, and biochemistry data were compared between groups. RESULTS: Cold ischemia time did not differ between groups (902 min and 909 min, respectively). There were no differences in macroscopic findings regarding coloration and damage between groups. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in preservation fluid were graft weight-corrected and compared, and no significant differences were found between groups: AST/g (4.61 vs 4.81 IU/L), ALT/g (2.78 vs 2.92 IU/L), and ALP/g (39.1 vs 37.0 IU/L). Immunochemical staining showed no significant difference between groups for terminal deoxynucleotidyl transferase dUTP nick and labeling staining (141 vs 113 cells), CD163 (818 vs 870 cells), and TNF-α (1.25 vs 1.41 scores). CONCLUSIONS: The simulation experiment of organ transport for transplantation by drones was successfully conducted. There were no differences in the quality of livers transported by drones or other means. Further studies including large-animal experiments could lead to future clinical applications.

Three-dimensional human bile duct formation from chemically induced human liver progenitor cells.

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.

Preliminary Observations of An Ex Vivo Normothermic Whole Blood Machine Perfusion in An Experimental Liver Transplant Porcine Model.

BACKGROUND: Even though transplantation is an essential treatment with no viable alternatives, a significant worldwide donor shortage persists. In this study, we assessed the metabolism of livers that underwent extended periods of circulatory death and subsequently conducted functional validation through transplantation to explore the feasibility of using livers from an uncontrolled donor after circulatory death (u-DCD). METHODS: A donor model simulating u-DCD was constructed using pigs. The prolonged warm ischemia time (WIT) was set to 60, 120, and 180 minutes, and the liver function was evaluated after 24 hours of perfusion using an originally developed normothermic perfusion system. Based on the results, functional confirmation by transplantation was performed on the 2 groups with prolonged WIT of 60 and 180 minutes. RESULTS: Based on the 24-hour perfusion of the liver alone, we evaluated the function by transplanting the WI 60-minute model and 180-minute model (N = 3 each). Warm ischemia was 73.5 ± 3.7 minutes and 188 ± 3 minutes in the 60-minute model and 180-minute model, respectively. In the model with 60 minutes of WI, one case survived until the endpoint, and 2 cases survived between 8 and 12 hours, whereas, in the model with 180 minutes of WI, they died within 6 hours. CONCLUSION: We constructed a completely uncontrolled circulatory arrest model without anticoagulation and showed the possibility of using u-DCD livers by ex vivo machine perfusion and transplantation.

A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency.

BACKGROUND: The application of laparoscopic procedures in the liver surgery has been growing. We herein present the first case of a pediatric patient who underwent living donor liver transplantation (LDLT) using a hybrid procedure with hand-assisted laparoscopic mobilization of the liver, subsequent explantation of the diseased liver, and implantation of the graft under direct vision. METHODS: A 12-year-old girl with citrin deficiency was scheduled for LDLT with a left lobe graft. After making an 8-cm upper midline incision, a 5-mm trocar was placed at the umbilicus and the right upper abdomen. Mobilization of the right liver lobe was performed using a hand-assisted laparoscopic surgery (HALS) procedure. After the extension of the midline incision, short hepatic vein dissection, encircling the right hepatic vein and hepatic hilum dissection was performed. Explantation of the liver and subsequent implantation of the liver graft were conducted under direct vision. RESULTS: Since the operation, her normal activities of daily life have been maintained with a normal liver function. Subsequently, her secondary sexual characteristics have recovered without any wound-related complications. CONCLUSIONS: A hybrid LDLT procedure was feasible for a pediatric patient. This procedure's benefits are considered meaningful for pediatric patients as it does not disrupt the rectus muscles or nerves and achieves cosmesis.

Pathologic Complete Response after Chemotherapy with Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma with Tumor Thrombus in the Main Portal Trunk.

We report a case of pathologic complete response after successful treatment for advanced hepatocellular carcinoma (HCC) complicated with portal venous tumor thrombus with atezolizumab and bevacizumab followed by radical resection. The patient was a male in his 60s. During follow-up for chronic hepatitis B, abdominal ultrasonography revealed a huge tumor located in the right lobe of the liver with the portal vein thrombosed by the tumor. The tumor thrombus extended to the proximal side of the left branch of the portal vein. The patient's tumor marker levels were elevated (alpha-phetoprotein, 14,696 ng/mL; PIVKA-II, 2,141 mAU/mL). Liver biopsy revealed poorly differentiated HCC. The lesion was categorized as advanced stage according to the BCLC staging system. As systemic therapy, atezolizumab plus bevacizumab was administered. Imaging showed marked shrinkage of the tumor and portal venous thrombus with a remarkable decrease of tumor marker levels after 2 courses of chemotherapy. After 3 additional courses of chemotherapy, radical resection was considered possible. The patient underwent right hemihepatectomy and portal venous thrombectomy. A pathological examination revealed a complete response. In conclusion, we experienced a case in which advanced HCC was curatively treated with atezolizumab plus bevacizumab, which was administered as systemic therapy with a view to conversion surgery.

Percutaneous Direct Puncture of Retropancreatic Splenic Vein and Portal Thrombectomy in a Patient With Liver Transplantation and Simultaneous Splenectomy.

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.

Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co-infection: A nationwide survey in Japan.

AIM: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. METHODS: This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). RESULTS: All the patients were men with hemophilia, and the median age was 41 (range, 23-61) years. The median CD4 count before LT was 258 (range, 63-751). Most patients had poor liver function before surgery with Child-Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11-48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. CONCLUSION: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.

Most Cases of Cryptogenic Cirrhosis May Be Nonobese Nonalcoholic Steatohepatitis - Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study.

Objective The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of nonalcoholic steatohepatitis (NASH) in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; p=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, p=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; p=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; p=0.04). Conclusion Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis.

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.