Surgical text for orthotopic liver transplantation model with small-for-size graft in the pig: key techniques and pitfalls.

BACKGROUND: Challenges with small-for-size grafts are a critical issue in the liver transplantation field, and a reliable and reproducible animal model is required. METHOD: We performed 50 orthotopic liver transplantations in pigs with a 30% graft, and retrospectively investigated the learning curves. We modified our surgical procedures according to our experience. Here, we describe our current procedures in detail with retrospective evaluation of our experience. The artery to the right lateral lobe crosses the portal vein trunk. A 30% graft is taken using the right lateral lobe attached to a sufficient length of aorta. Hepatic venous plasty is undertaken on the back table to attach a venous patch to the anterior wall of the suprahepatic inferior vena cava, which has no extrahepatic margin. To minimize hypoperfusion to the digestive tract, an aorta-to-aorta anastomosis is performed in a side-to-end fashion in a minimal surgical field before suprahepatic inferior vena cava and portal vein reconstruction. A temporary transjugular portosystemic shunt is also inserted before suprahepatic inferior vena cava reconstruction. The recipient suprahepatic inferior vena cava is clamped at the intramediastinal level, including the margins of the diaphragm in the clamp. RESULTS: Although survival rate during first forty cases were under 0.2, a reasonable survival rate of 0.6 had been achieved after the experiences of forty cases. CONCLUSION: Precedent arterial reconstruction using an aorta-to-aorta anastomosis minimizes congestive damage and shortens operative time. Hepatic venous reconstruction should be completed without any outflow block, by using venous plasty and adequate clamping.

Significance of portal venous VEGF during liver regeneration after hepatectomy.

BACKGROUND: Although some studies have hypothesized portal venous blood is important for liver regeneration, no studies have established organs whose venous effluent flow into the portal vein secrete liver regenerating factors into the portal vein during liver regeneration. The aim of this study was to elucidate up-regulation of vascular endothelial growth factor (VEGF) in the portal vein, and expressions of hepatic regenerating factors in organs whose venous effluent flows into the portal vein during liver regeneration. MATERIALS AND METHODS: VEGF protein in systemic and portal venous blood, as well as expression of VEGF, hypoxia-inducible factor-1alfa (HIF-1alpha), hepatocyte growth factor (HGF), and HGF activator (HGFA) mRNA were evaluated in the regenerating liver, spleen, and intestine following 70% partial hepatectomy (PHx) in rats. RESULTS: The portal VEGF protein level was significantly higher than the systemic level post-PHx (portal/systemic at 72, 120, and 168 h post-PHx: 17.2/13.0, 20.2/12.8, and 24.0/14.7 pg/mL; P = 0.003, P = 0.022 and P = 0.032, respectively). VEGF mRNA expressions were significantly higher in the liver (P = 0.000027: 168 h), spleen (P = 0.000059: 72 h) and intestine (P = 0.01: 24-72 h) post-PHx compared with pre-PHx. HIF-1alpha, HGF, and HGFA mRNA expressions in the liver, intestine, and spleen were also significantly higher post-PHx compared to pre-PHx. CONCLUSIONS: Portal VEGF was significantly higher than systemic VEGF, and expressions of VEGF, HIF-1alpha, HGF, and HGFA mRNA in the liver, spleen and intestine were also up-regulated during liver regeneration. These results suggest that hepatic regenerating factors derived from the spleen or intestine may contribute liver regeneration.

Assessment of cardiac output in liver transplantation recipients.

BACKGROUND: Liver cirrhosis causes peculiar systemic hemodynamics, and accurate evaluation of systemic hemodynamic state is important for cirrhotic recipients who underwent living donor liver transplantation (LDLT). We investigated the clinical advantages of a novel non-invasive method for measuring systemic hemodynamic parameters using indocyanine green (ICG). METHODS: Twenty-eight LDLT recipients were evaluated. Simultaneous measurements of cardiac output (CO) using Swan-Ganz catheters and pulse dye densitometry (PDD) were performed every 12 hours after LDLT. A total of 155 sets of simultaneous CO measurements were obtained. RESULTS: The CO values obtained by PDD correlated well with those obtained by the invasive catheter technique. In addition, none of the recipients developed any side-effects, and we verified the safety of repeated ICG injections. ICG is safe, even for repeated use over time in the same recipient. Moreover, PDD can measure the blood volume (BV). CONCLUSIONS: Since the cirrhotic systemic hemodynamics characterized by high CO and large BV remains, even after LDLT, the ability to measure CO and BV in a non-invasive, simple and real-time manner using PDD has advantages for cirrhotic LDLT recipients.

Optimal systemic hemodynamic stability for successful clinical outcomes after adult living-donor liver transplantation: prospective observational study.

BACKGROUND AND AIM: Most living-donor liver transplantation (LDLT) recipients show characteristic systemic hemodynamics due to liver cirrhosis, and systemic hemodynamics after LDLT influenced postoperative graft function corresponding to outcomes. However, identities of optimal systemic hemodynamics for excellent outcomes and precise parameters for clinical strategy remain unclear. METHODS: Therefore, we performed prospective study in adult LDLT recipients from 2003. Hemodynamic parameters were prospectively recorded, and were analyzed in 40 recipients classified into three groups: cirrhotic (group I-C) or non-cirrhotic recipients (group I-NC) with good outcomes, and cirrhotic recipients (group II-C) without good outcomes. RESULTS: Group I-C retained characteristic hyperdynamics even after LDLT. However, absolute values of parameters revealed no significant differences between groups I-C and II-C, because group II-C also tended to show hyperdynamics. It is suggested that successful outcomes in cirrhotic recipients require maintenance of optimal hyperdynamic stability after LDLT, because cirrhotic vascular alterations still occurred. Because hemodynamic behaviors were different between groups I-C and I-NC, absolute values were also significantly different even in these successful two groups. Thus, absolute values themselves were not necessarily satisfactory for accurate evaluation of optimal hemodynamic stability. Cirrhotic hyperdynamics are symbolized in large blood volume (BV) circulated by high cardiac output (CO); therefore, we standardized CO against BV. CO/BV was significantly different between groups I-C and II-C, reflecting subtle variability of hyperdynamics in groups II-C, and was interestingly constant in the two successful groups. Therefore, CO/BV reliably evaluated optimal hemodynamic stability after LDLT, and accurately predicted outcomes. CONCLUSION: Identification of inappropriate hemodynamics after LDLT is advantageous to further improve LDLT outcomes.

Alloantigen-specific prolongation of allograft survival in recipient mice treated by alloantigen immunization following ultraviolet-B irradiation.

It is well documented that ultraviolet (UV) radiation present in sunlight suppresses immune responses. However, the majority of studies documenting the immunosuppressive effects of UV irradiation have been carried out in animals exposed to UV irradiation before immunization. Here, we report that recipient mice exposed to UV irradiation 7 days after immunization with a donor alloantigen exhibited prolongation of allograft survival in an alloantigen-specific manner. Recipient mice (H-2(b)) intravenously immunized with 2 x 10(7) allogeneic spleen cells (H-2(b/d)) 7 days before UV irradiation (40 kJ/m(2)) showed prolonged survival of allografts presenting the alloantigen used for sensitization (H-2(b/d)), but not third-party allografts (H-2(b/k)). Adoptive transfer experiments revealed that CD4(+) T cells in UV-irradiated recipients were responsible for this prolongation. CD4(+) T cells that could transfer the suppression produced large amounts of interleukin (IL)-10, but not IL-4. The effect of UV irradiation on alloantigen-specific immunosuppression was cancelled by administration of an anti-IL-10 monoclonal antibody. These results indicate that UV irradiation given after alloantigen immunization induces alloantigen-specific type 1 regulatory T cell-like regulatory T cells that prolong allograft survival and imply that the difficulties associated with predicting donor-related organ availability in transplantation can be dealt with, given the effectiveness of UV irradiation after immunization.

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 ICG) 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 MTT 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 K ICG. 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.

Hyperglycemia and diabetic renal change in a model of polyvinyl alcohol bioartificial pancreas transplantation.

OBJECTIVES: We have developed a bioartificial pancreas transplantation method using polyvinyl alcohol. Using this model, the relationship between hyperglycemia and parameters that represent renal function was investigated. METHODS: Plasma glucose, 1,5-anhydro-d-glucitol (1,5-AG), and renal factors including plasma urea nitrogen and creatinine levels, urine volume, glucose, and albumin were examined once a week for 9 weeks in diabetic mice with or without transplantation of encapsulated rat islets, and in normal C57BL/6 mice. The mesangial matrix fraction of the glomerulus was measured histologically. The mice were classified into 3 groups according to their mean plasma glucose levels as either severe (n = 17) or mild (n = 23) hyperglycemia or normoglycemia (n = 11). The plasma glucose, renal factors, and mesangial matrix fraction were tested by single and multiple regression analyses. RESULTS: Almost all the renal factors correlated significantly with mean plasma glucose and 1,5-AG levels. The level and duration of hyperglycemia estimated by the area under the curve above basal correlated most significantly with mesangial matrix fraction. CONCLUSIONS: Bioartificial pancreas transplantation significantly reduced the deterioration of renal factors. The 1,5-AG was useful to predict urine albumin loss. The level and duration of hyperglycemia determined the degree of renal damage, which were reduced by bioartificial pancreas transplantation.

Noradrenalin-secreting retroperitoneal schwannoma resected by hand-assisted laparoscopic surgery: report of a case.

A 66-year-old woman was admitted to our hospital for investigation of a retroperitoneal mass. She was asymptomatic but her serum noradrenalin and vanillylmandellic acid levels were increased remarkably. Computed tomographic angiography showed a mass in the left side of the superior mesenteric artery (SMA) divergence, 6 x 4 cm in size, supplied mainly by the left adrenal artery. We performed hand-assisted laparoscopic surgery (HALS) using a Cavitron ultrasonic surgical aspirator. Abdominal exploration revealed that the tumor was located in the left side of the SMA root, but was not adhered to the adjacent organs. Her vital signs remained stable during the operation. Microscopic examination revealed a palisade formation, confirming a histopathological diagnosis of degenerated schwannoma (Antoni type B). Immunohistologically, the tumor cells were stained with S-100 protein and neuron-specific enolase. Her noradrenalin level normalized immediately after the operation and she remains in good health 3 years 2 months later.

K(ICG) value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation.

Reliable monitoring enabling evaluation of graft function is crucial after living-donor liver transplantation (LDLT). A method to identify poor graft function at an early postoperative period would allow opportune intensive clinical management to bring about further improvements in LDLT outcomes. This study assessed the reliability of the indocyanine green (ICG) elimination rate constant (K(ICG)) value as an estimator of graft function and determined the actual temporal changes of K(ICG) after LDLT. K(ICG) values were measured using a noninvasive method in 30 adult recipients up to 28 days after LDLT. The receptor index (LHL15) based on liver scintigraphy, and graft parenchymal damage score based on histopathological findings were evaluated after LDLT and correlated well with simultaneous K(ICG). Thus, K(ICG) measured by noninvasive method was confirmed as accurately evaluating graft function. Changes of K(ICG) after LDLT in recipients with good graft function were maintained, after some falls in the early periods, and had a significant difference compared with those for recipients without good graft function; moreover, there were already significant differences in K(ICG) 24 hours after LDLT. Mean transit time reflecting systemic hemodynamics revealed that recipients without good outcomes fell into an unstable systemic hemodynamic state, and effective hepatic blood flow has a large influence on liver regeneration after LDLT. In conclusion, we suggested that K(ICG) values can predict clinical outcomes at the early postoperative period after LDLT by sharply reflecting the influence of systemic dynamics on splanchnic circulation.