Living-related liver transplantation for Alagille syndrome

Alagille syndrome (AGS) is an autosomal dominant genetic disorder characterized by chronic cholestasis, congenital heart disease, peculiar facies, butterfly-like vertebrae, and posterior embryotoxon. Liver dysfunction is the common presentation of AGS, and liver transplantation may be indicated. This study examines the outcome of living-related liver transplantation (LRLT) for AGS. Twenty patients with AGS (median age 5.0 years, range 0.6-12.9) underwent LRLT at Kyoto University Hospital between June 1990 and February 2002. Five potential donors were excluded because of paucity of intrahepatic bile ducts diagnosed by preoperative liver biopsy and one because of a hepatic vascular anomaly. The overall 5-year patient survival was 80.4%. Three patients died as the result of the following: complications related to surgery, heart failure caused by progressive pulmonary artery stenosis, and a graft with unsuspected bile duct paucity. Liver dysfunction was improved in all successful cases, and catch-up growth occurred in 90% of patients. LRLT is an efficacious treatment modality for AGS if donors are selected by cautious evaluation to rule out unsuspected bile duct paucity.     

Biliary anastomotic complications in 400 living related liver transplantations

The purpose of this study was to evaluate the cause and outcome of biliary anastomotic complications occurring after living related liver transplantation (LRLT). A database of 391 patients undergoing 400 LRLT from June 1990 to August 1998 was reviewed. The overall incidence of biliary anastomotic complications was 18.2% (71 patients). There were 45 bile leaks, 35 anastomotic strictures, and the bile duct was ligated inadvertently in 3 cases. Univariative analysis revealed that the manner of stent usage, intrapulmonary shunting, and gender of recipients were significant risk factors for leakage. Anastomotic leaks, cytomegalovirus infection, hepatic artery complications, and gender of recipients were significant risk factors for stricture. In pediatric patients older than 2 years old, ABO blood type compatibility was another risk factor for leakage and stricture. Choice of stent usage and earlier transplantation for patients with intrapulmonary shunting should reduce the rate of biliary leaks, and prophylaxis of leaks for patients with intrapulmonary shunting, and minimizing hepatic artery complications should reduce the rate of biliary stricture after LRLT. Avoidance of ABO-incompatible donors or innovative immunosuppression in ABO-incompatible transplantation should be considered in children.     

Pathogenesis and treatment of bile duct loss after liver transplantation

The bile duct is one of the main targets of immune reaction after liver transplantation. Bile duct loss, termed ductopenia or vanishing bile duct syndrome, is a typical pathological finding of chronic rejection (CR). The mechanism of bile duct loss in allograft rejection is twofold: T-cell mediated cytotoxicity and ischemic sequelae caused by obliterative arteriopathy. Whether or not CR is reversible remains controversial. Accumulating data show the reversibility of bile duct injury caused by immunoreaction, but not the reversibility of injuries caused by ischemia. In our living-related liver transplantation program at Kyoto University Hospital, the incidence of ductopenia, which indicates the incidence of CR, was 14 of 423 patients (3.3%), comparable to the result for cadaveric liver transplantation. The onset was within 1 year, except in 2 patients. Of the 14 patients with ductopenia, 2 recovered without re-transplantation, and of the remaining 12 patients, 7 underwent re-transplantation, and the other 5 died without a chance of re-transplantation. The diagnosis of ductopenia was based on the pathological findings, which specify that more than 50% of the portal triad does not contain visible bile ducts. Recently, staging criteria of CR were proposed by an international panel, who recommended splitting CR into an early stage and a late stage. At present, no specific immunosuppressive regimen for CR has been developed; however, early diagnosis based on these new criteria, and the earlier implementation of enforced immunosuppression, with conventional drugs, may be beneficial for a further reduction in CR. Received: November 16, 2000 / Accepted: January 10, 2001     

Graft size assessment and analysis of donors for living donor liver transplantation using right lobe

BACKGROUND: Modality of living donor liver transplantation (LDLT) has been expanded to adult cases. However, the safety of right lobectomy from living donors has not yet been proven. METHODS: A total of 62 cases of LDLT, using the right lobe, were reviewed. Study 1: Discrepancy between estimated graft volume and actual graft weight was evaluated. Study 2: Postoperative liver functions were analyzed in relation to residual liver volume (RLV) or age. Residual liver volume of donors was defined using two indices, (RLV = estimated whole liver volume - estimated graft volume and %RLV = RLV/estimated whole liver volumex100). Donors were divided into two groups on the basis of either %RLV (<40%; 40%< or =) or age (<50 years old; 50 years old < or =). Study 3: Right lobe donors were compared with left lobe donors (35 cases) in terms of their postoperative liver functions. RESULTS: Study 1: The relationship between estimated graft volume and actual graft weight was linear (y=159.136+0.735x, R2=0.571, P<0.001). Study 2: %RLV ranged from 23.5% to 55.8% (mean +/- SD: 43.2+/-6.0). Fifteen cases showed %RLV less than 40%. Postoperative bilirubin clearance was delayed in that group (%RLV<40%). Serum total bilirubin values on postoperative day 7 in the older group (age > or =50) were significantly higher than those in the younger group (age<50). Study 3: Postoperative liver functions of right lobe donors were significantly higher than those of left-lobe donors. Eleven donors (17.7%) had surgical complications, all of which were cured with proper treatment. CONCLUSIONS: Right lobectomy from living donors is a safe procedure with acceptable morbidity, but some care should be taken early after the operation for donors with small residual liver and aged donors.     

Weaning of immunosuppression in living donor liver transplant recipients

BACKGROUND: Some reported studies have indicated the possibility of immunosuppression withdrawal in cadaveric liver transplantation. The aim of this study was to evaluate the possibility and feasibility of weaning living donor liver transplant recipients from immunosuppression. METHODS: From June of 1990 to October of 1999, 63 patients were considered to be weaned from immunosuppression. They consisted of 26 electively weaned patients and 37 either forcibly or incidentally weaned patients (nonelective weaning) due to various causes but mainly due to infection. Regarding elective weaning, we gradually reduced the frequency of tacrolimus administration for patients who survived more than 2 years after transplantation, maintained a good graft function, and had no rejection episodes in the preceding 12 months. The frequency of administration was reduced from the conventional b.i.d. until the start of weaning to q.d., 4 times a week, 3 times a week, twice a week, once a week, twice a month, once a month, and finally, the patients were completely weaned off with each weaning period lasting from 3 to 6 months. The reduction method of nonelective weaning depended on the clinical course of each individual case. When the patients were clinically diagnosed to develop rejection during weaning, then such patients were treated by a reintroduction of tacrolimus or an additional steroid bolus when indicated. RESULTS: Twenty-four patients (38.1%) achieved a complete withdrawal of tacrolimus with a median drug-free period of 23.5 months (range, 3-69 months). Twenty-three patients (36.5%) are still being weaned at various stages. Sixteen patients (25.4%) encountered rejection while weaning at median period of 9.5 months (range, 1-63 months) from the start of weaning. All 16 were easily treated with the reintroduction of tacrolimus or additional steroid bolus therapy. CONCLUSIONS: We were able to achieve a complete withdrawal of immunosuppression in some selected patients. Although the mechanism of graft acceptance in these patients has yet to be elucidated, we believe that a majority of long-term patients undergoing living donor liver transplantation may, thus, be potential candidates to be successfully weaned from immunosuppression.     

Microcirculatory changes in right lobe grafts in living-donor liver transplantation: a near-infrared spectrometry study

BACKGROUND: A continuing shortage of cadaveric liver even for adult patients has motivated not a few centers to proceed to living-donor liver transplantation using right lobe grafts. One of controversies is potential congestion in the graft anterior segment by the deprivation of the middle hepatic vein. METHODS: Hepatic tissue oxygenation and hemoglobin concentration were investigated with a near-infrared spectroscopy in the course of harvesting and implantation in living-donor liver transplantation. Twenty adult recipients of right lobe graft were involved in the study. The aim of the analysis was to detect tissue congestion or ischemia. RESULTS: No significant change in mean hepatic tissue oxygenation and hemoglobin was noted in the right lobe during donor operation even after hepatic parenchymal transection, although some trend for relative congestion, i.e., increased tissue hemoglobin, compared with the left lobe was observed. After graft reperfusion in the recipient, both mean hepatic tissue oxygen saturation and hemoglobin decreased significantly in the anterior segment, which was accompanied by increased heterogeneity of tissue hemoglobin and oxygenation. Increased heterogeneity of oxygenation and decreased tissue hemoglobin were observed also in the posterior segment. CONCLUSIONS: The anterior segment in right lobe living-donor liver transplantation is sensitive to ischemia, rather than congestion, at least in the immediate phase after graft reperfusion. The anterior segment seems to be also more prone to circulatory disturbance than the other part of the graft.     

产后出血的预防和处理指南

目的:为产后出血(PPH)的预防和临床处理作一综述,为临床医师提供预防和处理产后出血的指南。涉及方面:预防、适当干预、使其影响最小化的方法。结果:建立常规,便于临床医师鉴别可能的高危人群,一旦发生产后过多出血,可指导临床如何迅速处理。证据:遵循加拿大定期健康检查办公室制定的证据等级。评估:由产科专家完善。利弊和成本:评估子宫收缩药和其他积极处理措施的方便性、正确性、有效性和安全性。建议:根据证据的等级,本指南分等级列出了12条建议。确认:按照MeSH词表推荐的postpartum haemorrhage在medline上查询相关文献,在Cochrane图书馆查找相关研究文献,并参考the ALARMcourse Manual。发起人:由产科临床实践委员会制定和综述,并由SOGC(加拿大妇产科协会)委员会批准。     

Preparation and clinical evaluation of orally-disintegrating clonidine hydrochloride tablets for preanesthetic medication

Orally-disintegrating tablets of clonidine hydrochloride, an alpha 2-adrenergic agonist, were prepared by the method of drying an aqueous suspension. The suspension was prepared using powdered lactose, and the composition ratio was 2:1 (powdered lactose: 0.048% clonidine hydrochloride solution). The suspension was dried under 4 +/- 1 degrees C (72 +/- 15% R.H.). We obtained tablets containing clonidine hydrochloride (40 micrograms/tablet). Physical properties of the tablets were as follows: hardness was 4.0 kgf, and disintegration time was 41.7 s (in vitro). In the clinical use, 8 patients, aged 1-2 year and weighing 9-11 kg, received approximately 4 micrograms/kg body weight as clonidine hydrochloride. The tablet was administered 90 min before entering the operating room. All patients were willing to accept the tablet. The quality of separation from parents, sedation and a mask acceptance were excellent on all patients. These results suggest that the orally-disintegrating tablet of clonidine hydrochloride was useful in a clinical situation for the preanesthetic medication of pediatric patients aged 1-2 year.     

Congenital isolated thyrotrophin releasing hormone deficiency

A 4⅓-year-old girl with congenital thyrotrophin-releasing hormone (TRH) deficiency is described. Oral TRH administration led to normal thyroid hormone and TRH levels in the blood; favourable growth and development was achieved.