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.

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis

AIM： To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation （LDLT）, and to clarify how systemic hemodynamics impact on local graft circulation after LDLT.METHODS： Systemic hemodynamics, indocyanine green （ICG） elimination rate （K,cG） and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry （PDD） and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output （CO） to blood volume （BV） and mean transit time （MTT）, defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function.RESULTS： Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance （TPR） were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and M＇IT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow.CONCLUSION： We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.

Ultraviolet-induced alloantigen-specific immunosuppression in transplant immunity

After the first observation of the immunosuppressive effects of ultraviolet(UV) irradiation was reported in 1974, therapeutic modification of immune responses by UV irradiation began to be investigated in the context immunization. UV-induced immunosuppression is via the action of regulatory T cells(Tregs). Antigen-specific Tregs were induced by high-dose UV-B irradiation before antigen immunization in many studies, as it was considered that functional alteration and/or modulation of antigen-presenting cells by UV irradiation was required for the induction of antigen-specific immunosuppression. However, it is also reported that UV irradiation after immunization induces antigen-specific Tregs. UV-induced Tregs are also dominantly transferable, with interleukin-10 being important for UV-induced immunosuppression. Currently, various possible mechanisms involving Treg phenotype and cytokine profile have been suggested. UV irradiation accompanied by alloantigen immunization induces alloantigen-specific transferable Tregs, which have potential therapeutic applications in the transplantation field. Here we review the current status of UV-induced antigen-specific immunosuppression on the 40th anniversary of its discovery.

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.

Carcinoembryonic antigen-producing adrenal adenoma resected using combined lateral and anterior transperitoneal laparoscopic surgery

A 74-year-old woman presented with symptoms consistent with hyperadrenocorticism and hyperca- techolaminism. She had a cushingoid appearance and her cortisol level was elevated. Her serum dopamine and noradrenalin levels were also elevated. Computed tomography detected a left adrenal mass measuring 3.5 cm x 3.0 cm in diameter. Metaiodobenzylguanidine scintigraphy was negative. Unexpectedly, the serum Serum carcinoembryonic antigen （CEA） level waselevated. Fluorodeoxyglucose positron emission tomography showed increased uptake in the adrenal tumor only, with a maximum standardized uptake value of 2.8. Selective venography and blood sampling revealed that the concentrations of cortisol, catecholamines and CEA were significantly elevated in the vein draining the tumor. A diagnosis of CEA-producing benign adenoma was made. After preoperative management, we performed a combined lateral and anterior transpedtoneal laparoscopic adrenectomy. Her vital signs remained stable during surgery. Histopathological examination revealed a benign adenoma. Her cortisol, catecholamine and CEA levels normalized immediately after surgery. We present, to the best of our knowledge, the first case of CEA-producing adrenal adenoma, along with a review of the relevant literature, and discuss our laparoscopic surgery techniques.

How Specialists Become Primary Care Physicians in Japan

Background: Most countries have a shortage of Primary Care (PC) physicians. Japan has mitigated this problem by specialists making a mid-career change to PC when they go into private practice. This study examines the circumstances under which specialists shift to PC. Methods: Since the division between specialists and PC physicians is blurred in Japan, we focus on Physicians Providing Home Visits (PPHV). The list of PPHV was obtained from the local medical associations in two neighboring medical planning areas in Japan. The methods used were a questionnaire and in-depth interviews. Results: Of the 46 listed as PPHV, 38 responded to the questionnaires. Physicians mainly acquired their knowledge and skills in primary care from post-graduate clinical training and on the job training after becoming PPHV. The specialists who had moved to PC were equally knowledgeable regarding PC as those had taken the PC accreditation exam. The in-depth interviews revealed that the higher income earned in clinics and being able to retain their identity as a specialist were also important factors. Conclusions: The factors that contributed to physicians making a mid-career change from specialists to PC were their experiences after being certified, the higher income in clinics and the ability to retain their professional identity as specialists. These enabling factors might also be applicable for increasing the ratio of PC physicians at the global level although further studies are required.

Numerical investigation of an active TPS for a wing leading edge exposed to high temperature air behind a strong bow shock wave

An array of subsonic counter-flow jets is studied as an active thermal protection system(TPS)for wing leading edges of hypersonic vehicles.The performance is numerically estimated in the model case of a circular cylinder on the basis of the 2D compressible Navier-Stokes equations.In contrast to a single subsonic jet,an array of jets is robust against variation of the angle of attack;high cooling effectiveness is confirmed up to 5°variation.The coolant gas(air)discharged from channels embedded in the cylinder covers over a wide range of the front surface of the cylinder.The feasibility of the active TPS is also discussed.