Shinichiro Ono

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

ABSTRACT Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.

Evaluation of SOX9 Expression in Pancreatic Ductal Adenocarcinoma and Intraductal Papillary Mucinous Neoplasm

Objectives Sex-determining region Y (SRY) box 9 (SOX9) is an important transcription factor required for development and has been implicated in several types of cancer. Sex-determining region Y box 9 has never been linked to pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The aim of this study was to investigate the relationship between SOX9 and PDAC and that between SOX9 and IPMN. Methods Surgical specimens were obtained from 55 patients with PDAC and 68 patients with IPMN and were investigated using SOX9 immunohistochemical analysis. Results The rate of SOX9 positive cells to total pancreatic duct epithelial cells in a normal pancreas was 82.7%. On the other hand, the SOX9 positive rate in PDAC was 0.8%. There was a significant difference between the normal pancreas and PDAC (P = 0.0002). In IPMN, the SOX9 positive rate gradually decreased according to tumor progression, with the following rates observed: intraductal papillary mucinous adenoma (66.3%); noninvasive intraductal papillary mucinous carcinoma (46.3%); minimally invasive intraductal papillary mucinous carcinoma (30.5%); and invasive carcinoma originating in intraductal papillary mucinous carcinoma (2.3%). There were significant differences between each group (P < 0.05). Conclusions Our data suggested that SOX9 might contribute to carcinogenesis in PDAC and IPMN.

Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors

ABSTRACT The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post-transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8–10 hours, and donor age 50–60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues.

Endoscopic transpapillary pancreatic stenting for internal pancreatic fistula with the disruption of the pancreatic ductal system

BACKGROUND Internal pancreatic fistula (IPF) is a well-recognized complication of pancreatic diseases. Although there have been many reports concerning IPF, the therapy for IPF still remains controversial. We herein report our experiences with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its validity. METHOD Six patients with IPF who presented at our department and received endoscopic transpapillary pancreatic stent therapy were investigated, focusing on the clinical and imaging features as well as treatment strategies, the response to therapy and the outcome. RESULTS All patients were complicated with stenosis or obstruction of the main pancreatic duct, and in these cases the pancreatic ductal disruption developed distal to the areas of pancreatic stricture. The sites of pancreatic ductal disruption were the pancreatic body in five patients and the pancreatic tail in one patient. All patients received endoscopic stent placement over the stenosis site of the pancreatic duct. Three patients improved completely and one patient improved temporarily. Finally, three patients underwent surgical treatment for IPF. All patients have maintained a good course without a recurrence of IPF. CONCLUSION Endoscopic transpapillary pancreatic stent therapy may be an appropriate first-line treatment to be considered before surgical treatment. The point of stenting for IPF is to place a stent over the stenosis site of the pancreatic duct to reduce the pancreatic ductal pressure and the pseudocysts pressure.

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are known to have a protective effect on islet cells. Cell sheets developed using tissue engineering help maintain the function of the cells themselves. This study describes a tissue engineering approach using islets with MSC sheets to improve the therapeutic effect of islet transplantation. MSCs were obtained from Fischer 344 rats and engineered into cell sheets using temperature-responsive culture dishes. The islets obtained from Fischer 344 rats were seeded onto MSC sheets, and the islets with MSC sheets were harvested by low-temperature treatment after coculture. The functional activity of the islets with MSC sheets was confirmed by a histological examination, insulin secretion assay, and quantification of the levels of cytokines. The therapeutic effects of the islets with MSC sheets were investigated by transplanting the sheets at subcutaneous sites in severe combined immunodeficiency (SCID) mice with streptozotocin-induced diabetes. Improvement of islet function and viability was shown in situ on the MSC sheet, and the histological examination showed that the MSC sheet maintained adhesion factor on the surface. In the recipient mice, normoglycemia was maintained for at least 84 days after transplantation, and neovascularization was observed. These results demonstrated that islet transplantation in a subcutaneous site would be possible by using the MSC sheet as a scaffold for islets.

Successful laparoscopic repair of a lumbar hernia occurring after iliac bone harvest.

Introduction Many techniques have been described for the surgical repair of lumbar hernias, including primary repair, local tissue flaps, and conventional mesh repair. All these open techniques require a large incision plus extensive dissection to expose the hernia ring. This report presents a case of a recurrent lumbar hernia, which was successfully repaired using a laparoscopic approach. Case Report A 75-year-old female presented with a symptomatic right lumbar hernia, 1-year after an iliac bone harvest for knee surgery. Under general anesthesia, the patient was placed in a lateral decubitus position. A 3 trocar technique was used to do adhesiolysis of the surrounding tissues, to provide an ample working space to identify the hernia. A composix dual mesh (bard) was tailored so that it would overlap the defect with intermittent fixation by a spiral tacker (protac). No hernia recurrence occurred over 2 years after surgery. Conclusion The laparoscopic approach has significant advantages for the repair a lumbar hernia: it enables the exact localization of the anatomic defect, and the mesh can be placed deep into the defect, thus allowing the intraabdominal pressure to hold it in position.

Technical Progress in Single-Incision Laparoscopic Cholecystectomy in Our Initial Experience

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.

Analysis of early relaparotomy following living donor liver transplantation

We retrospectively analyzed the causes, risk factors, and impact of early relaparotomy after adult‐to‐adult living donor liver transplantation (LDLT) on the posttransplant outcome. Adult recipients who underwent initial LDLT at our institution between August 1997 and August 2015 (n = 196) were included. Any patients who required early retransplantation were excluded. Early relaparotomy was defined as surgical treatment within 30 days after LDLT. Relaparotomy was performed 66 times in 52 recipients (a maximum of 4 times in 1 patient). The reasons for relaparotomy comprised postoperative bleeding (39.4%), vascular complications (27.3%), suspicion of abdominal sepsis or bile leakage (25.8%), and others (7.6%). A multivariate analysis revealed that previous upper abdominal surgery and prolonged operative time were independent risk factors for early relaparotomy. The overall survival rate in the relaparotomy group was worse than that in the nonrelaparotomy group (6 months, 67.3% versus 90.1%, P < 0.001; 1 year, 67.3% versus 88.6%, P < 0.001; and 5 years, 62.6% versus 70.6%, P = 0.06). The outcome of patients who underwent 2 or more relaparotomies was worse compared with patients who underwent only 1 relaparotomy. In a subgroup analysis according to the cause of initial relaparotomy, the survival rate of the postoperative bleeding group was comparable with the nonrelaparotomy group (P = 0.96). On the other hand, the survival rate of the vascular complication group was significantly worse than that of the nonrelaparotomy group (P = 0.001). Previous upper abdominal surgery is a risk factor for early relaparotomy after LDLT. A favorable longterm outcome is expected in patients who undergo early relaparotomy due to postoperative bleeding. Liver Transplantation 22 1519–1525 2016 AASLD.

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function In Vitro.

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.

Simultaneous Pancreas and Kidney Composite Graft Transplantation with Retroperitoneal Systemic-Enteric Drainage

BACKGROUND Simultaneous pancreas and kidney transplantation is the treatment of choice for diabetes mellitus patients with associated end-stage renal disease. Limited vascular access could be encountered in patients with severe atherosclerosis, and/or severe obesity and in re-transplant patients. We describe a modified technique that facilitates simultaneous pancreas and kidney (SPK) composite graft transplantation with retroperitoneal systemic-enteric drainage for patients with limited vascular access. MATERIAL/METHODS Since April 2012, we performed a modified technique for 2 patients with limited vascular access. SPK composite graft was constructed during the back-table preparation and transplanted in the right retroperitoneal space, finally covered by the ascending colon and its mesocolon. RESULTS The 2 patients achieved good pancreas grafts function with normal blood glucose immediately after the completion of reperfusion. Their kidney grafts have also shown good function. They have not had any rejection episodes or postoperative complications after the SPK composite graft transplantation. CONCLUSIONS We propose that simultaneous pancreas and kidney composite graft transplantation with retroperitoneal systemic-enteric drainage can be a viable option for patients with limited vascular access.