Comprehensive and innovative techniques for livertransplantation in rats: A surgical guide

AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries.RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model.

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vectormediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

Diagnosis and management of fibromuscular dysplasia and segmental arterial mediolysis in gastroenterology field: A mini-review

The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia(FMD) and segmental arterial mediolysis(SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation:A single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Impact of continuous local lavage on pancreatic juice-related postoperative complications: Three case reports

BACKGROUND Postoperative pancreatic leakage readily results in intractable pancreatic fistula and subsequent intraperitoneal abscess.This refractory complication can be fatal;therefore,intensive treatment is important.Continuous local lavage (CLL) has recently been reevaluated as effective treatment for severe infected pancreatitis,and we report three patients with postoperative intractable pancreatic fistula successfully treated by CLL.We also discuss our institutional protocol for CLL for postoperative pancreatic fistula.CASE SUMMARY The first patient underwent subtotal stomach-preserving pancreaticoduodenectomy,and pancreatic leakage was observed postoperatively.Intractable pancreatic fistula led to intraperitoneal abscess,and CLL near the pancreaticojejunostomy site was instituted from postoperative day (POD) 8.The abscess resolved after 7 d of CLL.The second patient underwent distal pancreatectomy.Pancreatic leakage was observed,and intractable pancreatic fistula led to intraperitoneal abscess near the pancreatic stump.CLL was instituted from POD 9,and the abscess resolved after 4 d of CLL.The third patient underwent aneurysmectomy and splenectomy with wide exposure of the pancreatic parenchyma.Endoscopic retrograde pancreatic drainage was performed on POD 15 to treat pancreatic fistula;however,intraperitoneal abscess was detected on POD 59.We performed CLL endoscopically via the transgastric route because the percutaneous approach was difficult.CLL was instituted from POD 63,and the abscess resolved after 1 wk of CLL.CONCLUSION CLL has therapeutic potential for postoperative pancreatic fistula.

Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis

As for resection for colorectal liver metastasis (CRLM), secur-ing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve ade-quate margins for the resection of CRLM. So the current sur-vival impact of sub-centi/millimeter surgical margins in he-patectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the sur-gical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diag-nosed as having CRLM. We focused on studies that investi-gated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly de-scribe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submil-limeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm mar-gins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, fur-ther study is warranted.

Toward Seamless Indoor-Outdoor Applications:Developing Stakeholder-Oriented Location-Based Services

Location-Based Services (LBS),an emerging new business based on smartphone and mobile networks,are becoming more and more popular.Most of these LBSs,however,only offer non-seamless indoor/outdoor applications and simple applications without giving stakeholders the chance to play an active role.Our specific aim is to solve these issues.This paper presents concepts to solve these issues by expanding the Open Location Services Interface Standard (OpenLS) to allow seamless indoor/outdoor positioning and to extend the content of the services to include information recommended by stakeholders.

Long-term health-related quality of life of living liver donors:what should the transplant team know?

Living-donor liver transplantation(LDLT)has been established as an alternative to deceased donor liver transplantation as a treatment option for patients with end-stage liver disease.Especially in Japan,where the number of deceased donor liver transplants is extremely small compared to Western countries,LDLT still accounts for the majority of liver transplants.