Takayuki Anazawa

Portal vein reconstruction using vein grafts in pediatric living donor liver transplantation: Current status

PV reconstruction is an important aspect of LDLT, with post‐transplant outcomes depending on PV reconstruction methods. However, it is unclear whether the preferential selection of these techniques is dependent on preoperative recipient characteristics. This retrospective study assessed whether preoperative recipient factors differed in pediatric patients who did and did not receive VGs for PV reconstruction. Of 113 pediatric patients who underwent LDLT from January 2010 to July 2015, 31 (27%) underwent PV reconstruction with VGs and the other 82 (73%) without VGs. The presence of collateral vessels (P<.0001) and ascites (P=.02); PV size (P<.001), thrombosis (P=.01) and the direction of flow (P=.01), Child‐Pugh class A vs B/C liver function (P=.01), Alb concentration (P=.02), primary diagnosis: BA vs non‐BA (P=.03), and previous abdominal surgery (P<.005) differed significantly in patients who did and did not receive VGs for PV reconstruction. PV complications, patient survival, and graft survival did not differ significantly in patients with and without VGs at 1‐year follow‐up. VGs should be harvested for recipients with pretransplant hypoplastic PV, intense collaterals, hepatofugal flow, poor liver status, or previous abdominal surgery.

Successful laparoscopic distal pancreatectomy for a large solid pseudopapillary neoplasm: A case report

A 30‐year‐old Japanese woman presented at our hospital with a pancreatic tumor. Contrast‐enhanced CT revealed a tumor with a 12‐cm diameter in the pancreatic body and tail. In the preoperative setting, endoscopic ultrasound‐guided fine‐needle aspiration permitted a histopathological diagnosis of solid pseudopapillary neoplasm. Twhe patient underwent laparoscopic distal pancreatectomy with splenectomy. Our procedure involved three steps. Firstly, the splenic artery was occluded to block inflow of blood to the tumor. Then, we transected the neck of the pancreas using radical antegrade modular pancreatosplenectomy. Finally, hand‐assisted laparoscopic surgery allowed us to secure the operating field and easily handle the large tumor. This enabled us to accomplish laparoscopic distal pancreatectomy, and en‐bloc resection was completed. The patient was discharged without major complications. Laparoscopic distal pancreatectomy for huge solid pancreatic tumors can be completed safely.

Future Perspectives for the Treatment of Diabetes: Importance of a Regulatory Framework

Background: The number of diabetes patients is steadily increasing worldwide. Consequently, the social burden of diabetes is huge, requiring urgent countermeasures. We performed an intensive survey of antidiabetic drugs approved in Japan, the United States, and the European Union. Methods: Information about approved antidiabetic drugs was obtained by searching databases of regulatory authorities in the 3 regions. Other relevant information was also obtained from publicly available literature and documents. Results: No difference in the total number and types of approved drugs among the 3 regions was found (P = .173 by log-rank test). However, the numbers of approved dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in Japan were almost double of those in the other regions. The average sample size in clinical trials used for antidiabetic drug approval in Japan (1134 patients) was much smaller than that in the other regions (P < .001 by analysis of variance repeated measures test adjusted by the Holm method). Currently, 6 drugs with known modes of action are being developed for type 1 diabetes in Japan, whereas at the end of 2016, nearly 7-fold more products with novel modes of action were in clinical development in the United States. Conclusion: Antidiabetic drug development in Japan costs less than that in the other regions, although novel development is less active because of regulatory differences. To achieve better pharmacotherapy for diabetes, the regulatory framework requires careful consideration.

Is Muscle MELD a More Promising Predictor for Mortality After Living Donor Liver Transplantation

Background: To improve the outcome of living donor liver transplantation (LDLT), a scoring system that could predict accurately the patient and graft survival posttransplant is necessary. The aim of this study is to evaluate our previously proposed Muscle-model for end-stage liver disease (M-MELD) score and to compare it with the other available scores to find the best system that correlates with postoperative outcome after liver transplant. Methods: We retrospectively reviewed the data of 199 patients who underwent LDLT from January 2010 to July 2016 and calculated the preoperative MELD, MELD Na, the product of donor age and MELD (D-MELD), M-MELD, integrated MELD, and the balance of risk (BAR) score in all patients. The area under the receiver operating characteristics curves (AUCs) of each score was computed and compared at 3-, 6-months, and 1-year after LDLT. Results: The M-MELD, D-MELD, and integrated MELD had a good discriminative performance in predicting 3-month mortality after LDLT with AUCs > 0.7, while the M-MELD was the only score that showed a good discriminative performance in predicting 6-month and 1-year mortality after LDLT with AUCs > 0.7. Conclusion: Muscle-MELD score is a simple and useful predictor of patient survival after LDLT which showed a better predictive performance than other available scores.

Pancreaticoduodenectomy with the Superior Mesenteric Artery Approach: How I Do It

The superior mesenteric artery (SMA) approach to pancreaticoduodenectomy (PD) is considered extremely important for early determination of resectability with negative margins. In addition, transecting the feeding arteries, including the inferior pancreaticoduodenal (IPDA) and gastroduodenal (GDA) arteries, before division of the pancreas can reduce blood loss during surgery and is a reasonable method for performing oncologic resection. This approach has promoted the development of an “artery-first” technique. Several techniques have been described under the heading of “artery-first.” We use the “Tora-no-Ana” approach, which consists of division of the ligament of Treitz, an entry into the retroperitoneal space behind the pancreatic body, and circumferential dissection around the SMA, with preservation of the nerve plexus around the SMA to prevent intractable diarrhea. A hanging maneuver of the pancreatic body facilitates a good operative view through the “Tora-no-Ana” approach. The IPDA and GDA are divided before division of the pancreatic body. In this chapter, we describe our techniques of the “artery-first” approach to PD with a review of the literature.

Computer tomographic assessment of postoperative peripancreatic collections after distal pancreatectomy

BackgroundPeripancreatic collections occur frequently after distal pancreatectomy. However, the sequelae of peripancreatic collections vary from case to case, and their clinical impact is uncertain. In this study, the correlations between CT findings of peripancreatic collections and complications after distal pancreatectomy were investigated.MethodsNinety-six consecutive patients who had undergone distal pancreatectomy between 2010 and 2015 were retrospectively investigated. The extent and heterogeneity of peripancreatic collections and background clinicopathological characteristics were analyzed. The extent of peripancreatic collections was calculated based on three-dimensional computed tomography images, and the degree of heterogeneity of peripancreatic collections was assessed based on the standard deviation of their density on computed tomography.ResultsOf 85 patients who underwent postoperative computed tomography imaging, a peripancreatic collection was detected in 77 (91%). Patients with either a large extent or a high degree of heterogeneity of peripancreatic collection had a significantly higher rate of clinically relevant pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval 2.12–19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87–24.19, p = 0.0001, respectively).ConclusionsA large and heterogeneous peripancreatic collection was significantly associated with postoperative complications, especially clinically relevant postoperative pancreatic fistula. A small and homogenous peripancreatic collection could be safely observed.

Current state and future evolution of pancreatic islet transplantation

Pancreatic islet transplantation provides an effective treatment option for patients with type 1 diabetes (T1D) with intractable impaired awareness of hypoglycemia and severe hypoglycemic events. Currently, the primary goal of islet transplantation should be excellent glycemic control without severe hypoglycemia, rather than insulin independence. Islet transplant recipients were less likely to achieve insulin independence, whereas solid pancreas transplant recipients substantially had greater procedure‐related morbidity. Excellent therapeutic effects of islet transplantation as a result of accurate blood glucose level–reactive insulin secretion, which cannot be reproduced by current drug therapy, have been confirmed. Recent improvement of islet transplantation outcome has been achieved by refinement of the pancreatic islet isolation technique, improvement of islet engraftment method, and introduction of effective immunosuppressive therapy. A disadvantage of islet transplantation is that donors are essential, and donor shortage has become a hindrance to its development. With the development of alternative transplantation sites and new cell sources, including porcine islet cells and embryonic stem/induced pluripotent stem (ES/iPS)‐derived β cells, “On‐demand” and “Unlimited” cell therapy for T1D can be established.

Ex vivo Pretreatment of Islets with Mitomycin C: Reduction in Immunogenic Potential of Islets by Suppressing Secretion of Multiple Chemotactic Factors

Strategies to reduce the immunogenicity of pancreatic islets and to prevent the activation of proinflammatory events are essential for successful islet engraftment. Pretransplant islet culture presents an opportunity for preconditioning to improve outcomes of islet transplantation. We previously demonstrated that ex vivo mitomycin C (MMC) pretreatment and subsequent culture significantly prolonged graft survival. Fully understanding the biological process of pretreatment could result in the development of a protocol to improve the survival of islet grafts. Microarrays were employed to conduct a comprehensive analysis of genes expressed in untreated or MMC-treated rat islets that were subsequently cultured for 3 d. A bioinformatics software was used to identify biological processes that were most affected by MMC pretreatment, and validation studies, including in vivo and in vitro assay, were performed. The gene expression analysis identified significant downregulation of annotated functions associated with cellular movement and revealed significant downregulation of multiple genes encoding proinflammatory mediators with chemotactic activity. Validation studies revealed significantly decreased levels of interleukin 6 (IL-6), monocyte chemoattractant protein 3 (MCP-3), and matrix metallopeptidase 2 (MMP2) in culture supernatants of MMC-treated islets compared with controls. Moreover, we showed the suppression of leukocyte chemotactic activity of MMC-treated islets in vitro. We also showed that MMC-treated islets secreted lower levels of chemoattractants that synergistically reduced the immunogenic potential of islets. Histological and immunohistochemical analyses of the implant site revealed that infiltration of monocytes, CD3-positive T cells, and B cells was decreased in MMC-treated islets. In conclusion, the ex vivo pretreatment of islets with MMC and subsequent culture can reduce the immunogenic potential and prolong the survival of islet grafts by inducing the suppression of multiple leukocyte chemotactic factors.