Combined heart-lung-liver,double lung-liver,and isolated liver transplantation for cystic fibrosis in children

Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heartlung-liver (n = 4), sequential double lung-liver (n = 2), or bilateral lobar lung from a split left lung and reduced liver (n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2), and severe ascites (n = 2). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites (n =1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial survival was 85.7 % ± 2 % in group 1 at 1 year; it remained unchanged at 3 years and was 64.2 % at 5 years.     

Cystic Fibrosis Liver Disease: To Transplant or Not to Transplant?

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4–171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome.     

活体肝移植的胆道重建技术及并发症分析

目的 探讨活体肝移植的胆道重建方法及并发症防治措施.方法 回顾性分析77例活体肝移植临床资料,其中74例行右半肝移植(带肝中静脉29例,不带肝中静脉45例),左半肝带肝中静脉1例,左外叶切取2例.胆道重建采用胆肠吻合或供肝肝管与受体肝管端端吻合.结果 供肝断面1个胆管开口为54例,多个胆管开口为23例;胆肠吻合2例,胆管端端吻合75例,63例留置T管;术后总体胆道并发症发生率为36.4%(28/77),其中胆漏为10.4%(8/77),胆道狭窄为26.0%(20/77).供肝单支胆道以及单个吻合口术后胆道狭窄的发生率明显低于多支胆道及多个吻合口(P<0.05).8例胆漏病人经过B超指引穿刺引流全部治愈,20例吻合口狭窄病人经T管窦道放置支撑管或通过ERCP进行扩张,肝功能全部或部分好转.结论 活体肝移植供肝切取术中注意对断面胆管血供的保护以及尽可能获得单一的肝管开口可有效减少术后胆道并发症的发生;内镜和放射介入技术是治疗胆道并发症的有效手段.     

肝移植术后胆道并发症的介入治疗

目的探讨原位肝移植术后胆道并发症的介入治疗疗效。方法回顾性分析我院2002年6月至2005年9月诊治的173例原位肝移植患者的临床资料。结果术后出现胆道并发症14例(8.1%),其中胆管狭窄6例,胆管狭窄合并胆漏1例,胆泥淤积或结石3例,肝断面胆漏2例(劈离式肝移植患者),T管拔除后胆漏1例,Oddi括约肌功能失常1例。除1例胆道狭窄再次行肝移植,因发生严重感染导致肝功能衰竭死亡外,其余患者经介入治疗均获得满意的效果。结论介入治疗是诊断和治疗肝移植术后胆道并发症的首选方法。     

肝移植术后肝内弥漫性胆管狭窄的治疗和预防

目的 探讨肝移植术后肝内弥漫性胆管狭窄的治疗及预防措施.方法 回顾性分析北京市器官移植中心2002年1月至2007年12月收治的21例肝移植术后肝内胆管弥漫性及肝内外多发性狭窄患者的临床资料.同时自2006年1月开始进行前瞻性研究,采用尿激酶灌注无心跳尸体供肝,预防肝内弥漫性胆管狭窄的发生.结果 21例患者中16例行再次肝脏移植,其余5例患者在等待供肝过程中因肝功能衰竭死亡.16例再次肝移植患者中14例治愈,患者健康状况良好,肝功能正常,2例死于围手术期真菌感染.尿激酶灌注组肝内弥漫性胆管狭窄的发生率1.4%,非尿激酶灌注组肝内弥漫性胆管狭窄的发生率5.9%,两组比较差异有统计学意义(x2=5.98,P<0.05).结论 再次肝移植是治疗难治性胆管狭窄的有效方法.对无心跳尸体供肝常规采用尿激酶两次灌洗方案能有效降低肝内胆管弥漫性狭窄的发生率.     

Elevated gamma-glutamyltransferase is associated with mortality in lung transplantation for cystic fibrosis

Cystic fibrosis (CF) is a life-threatening autosomal recessive hereditary disease, affecting multiple organs. In end stage disease, lung transplantation improves the quality of life and prolongs survival. CF liver disease (CFLD) as co-morbidity develops in 8-17% of CF patients. We aimed to investigate the impact of liver injury on prognosis following lung transplantation. Thirty-one patients with CF who underwent double lung transplantation (DLTx) from 1999 to 2009 were included. Post-transplant survival, liver serum parameters as well as INR, creatinine and the MELD-Score were determined preoperatively, 1 day and 4 weeks postoperatively. Prognostic impact of liver function on outcome was analysed. Mean patient age was 25 (15-38) and post-transplant 1 year-survival was 74%, 3 years 71% and 5 years 68%. Patients were grouped according to post-transplant survival, those deceased within the first year as group I (n = 8) and patients who survived longer as group II (n = 23). Group I exhibited significantly elevated gamma-glutamyltransferase (GGT), bilirubin and reduced platelets postoperatively. Low platelet count, increased bilirubin and GGT were associated with mortality after DLTx. Prospective studies are needed to determine a potential use and clinical implications for liver function tests in patients with CF before lung transplantation.     

The experience of biliary tract complications after liver transplantation

AIM: To report the morbidity and mortality of patients who undergo liver transplantation with or without T-tube implantation after choledochocholedochostomy as well as to discuss management of biliary complications. PATIENTS AND METHODS: We performed a retrospective review of 104 liver transplantations from August 2001 to February 2006, including 51 patients who underwent choledochocholedochostomy with a T-tube (group A) and 53, without a T-tube (group B). We compared the clinical characteristics, operative methods, biliary complications, morbidity, mortality, and management of complications. RESULTS: Between the two groups, there were no significant differences in clinical characteristics, including sex, age, and indication for liver transplantation (hepatitis B virus, hepatitis C virus, alcoholic liver cirrhosis, or hepatocellular carcinoma), Child-Pugh classification, Model for End-stage Liver Disease score, and operative macroscopic/microscopic findings. Additionally, there was no significant difference in biliary complications. Among these 104 patients, 14 (13.5%) developed biliary complications: seven anastomotic strictures, two intrahepatic duct strictures, two anastomotic stricture combined intrahepatic duct stricture, one bile leakage, one bile leakage combined with anastomotic stricture, and one external biliary compression. Nine patients with anastomotic stricture underwent endoscopy with a stent, which was successful only in two patients. The other six patients underwent choledochojejunostomy with excellent results. CONCLUSIONS: This study showed choledochocholedochostomy with or without a T-tube after liver transplantation did not influence the biliary complications. The biliary complications of anastomotic stricture after liver transplantation can be managed by endoscopy with a stent. If endoscopy fails, surgical intervention should be considered immediately.     

Magnetic resonance cholangiopancreatography for the accurate diagnosis of biliary complications after liver transplantation: comparison with endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography - long-term follow-up

Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.     

磁共振成像在肝移植术后并发症诊断中的应用

目的探讨磁共振成像在肝移植并发症诊断中的价值。方法回顾分析11例肝移植术后发生并发症者的磁共振检查影像资料。结果11例患者术后出现皮肤和巩膜黄染、发热以及尿黄等症状，丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶和胆红素升高．经B型超声波检查不能明确原因，采用磁共振（MRI、MRA和MRCP）检查，明确肝动脉吻合口狭窄1例；肝动脉闭塞2例；下腔静脉吻合口狭窄及血栓形成各1例；胆管吻合口狭窄4例，其中1例伴胆汁瘤形成；肝门水平非吻合口狭窄6例；肝坏死2例；肝包膜下血肿及右肾上腺出血各1例；均显示不等量的右侧胸腔积液、腹腔积液及肝门部水肿。结论磁共振一次检查可显示肝内外的多种结构，能为肝移植术后并发症的诊断提供丰富的肝脏、血管、胆道以及肝外结构的图像信息。     

成人良性终末期肝病肝移植术后中远期死亡的危险因素分析

目的 了解成人良性终末期肝病肝移植患者术后中远期的生存情况和导致中远期生存率下降的危险因素.方法 回顾性分析2003年10月至2007年6月行原位肝移植手术且术后存活时间超过1年的221例良性终末期肝病受者的资料,选取包括受者术前变量、供者变量、术中变量和受者术后变量共26个可能影响患者长期存活的危险因素,采用Cox回归分析筛选出影响肝移植受者术后长期存活的独立危险因素.结果 221例受者的随访率为97.3%(215/221),平均随访时间为(36.4±6.9)个月(12～56个月).其中28例在术后1年后死亡,主要死亡原因依次为感染(5.0%,11/221)、胆道并发症(3.6%,8/221)、乙型肝炎复发或再感染(1.4%,3/221).保留在Cox回归方程内的协变量为高龄(RR=2.325,P=0.009)、ABO血型(RR=2.206,P=0.015)、冷缺血时间(RR=3.001,P=0.000)、术后感染部位(RR=1.665,P=0.007)和胆道并发症(RR=2.655,P=0.004).结论 影响受者术后中远期存活的危险因素包括年龄≥60岁、ABO血型不符、冷缺血时间>12 h、术后肺部感染和移植肝胆管弥漫性狭窄.     

逆行胰胆管造影在肝移植中的应用

目的探讨经内镜逆行胰胆管造影(ERCP)在诊断和治疗肝移植术后胆道并发症中的应用。方法对本院肝移植术后出现胆道并发症的16例患者进行ERCP检查,并根据情况分别行鼻胆管引流(ENBD)和/或内镜下乳头切开取石(EST)等治疗。结果ERCP确诊16例肝移植术后胆道并发症,发生率为9.47%,其中胆道结石6例,胆道狭窄3例,吻合口漏2例,胆道结石伴左肝管狭窄1例,吻合口胆漏伴胆道结石3例,1例示供受体胆管比例不一致,供体胆管相对狭窄,所有患者都得到有效治疗。结论内镜下ERCP是诊断和治疗肝移植术后胆道并发症的一种安全而有效的手段,可作为非手术治疗中的首选。     

Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center's experience

Background: Improved long-term survival in cystic fibrosis (CF) has led to an increased incidence of extrapulmonary complications of this disease. Of these, end-stage liver disease is a significant cause of morbidity and mortality with liver transplantation being the only effective therapy.Methods: Records of all CF pediatric liver transplant recipients were reviewed.Results: Twelve children with CF were the recipients of 16 allografts. The 1- and 5-year survival was 91.6% and 75%, respectively. There were 5 deaths at a mean interval of 6.8 ± 6.3 years. All of these deaths were related to pulmonary disease. Pulmonary function improved or remained stable in 8 of 9 patients tested. Despite an 83% incidence of positive sputum cultures, there was only one early mortality related to pulmonary sepsis in the setting of primary liver allograft nonfunction.Conclusions: Liver transplantation is acceptable treatment for children with CF and end-stage liver disease. Long-term survival is comparable to liver transplantation performed for other indications. Although posttransplant morbidity and mortality is related to lung disease, the authors speculate that as therapeutic improvements prolong the survival in CF, it is expected that longer survival after liver transplantation in this patient population may also be anticipated.     

Spatulated end-to-end bile duct reconstruction in orthotopic liver transplantation

Biliary complications continue to be a major source of morbidity following orthotopic liver transplantation. The aim of this study was to analyze the incidence and management of biliary complications related to the technique of bile duct reconstruction. The patients were stratified into two groups: group I (n = 39) had bile duct reconstruction performed by an end-to-end single interrupted suture choledochocholedochostomy (EE-CDCD) and group II (n = 38) had a spatulated end-to-end CDCD (spEE-CDCD) reconstruction; both groups had an intraductal stent. The groups were similar in age, gender, liver transplant indications and Pugh score. Ten biliary complications (26%), including five bile leaks (13%) and five biliary strictures (13%), were observed in the EE-CDCD group, while one biliary stricture (2.6%) occurred in the spEE-CDCD group (p < 0.05). Subsequent imaging studies and endoscopic retrograde cholangiopancreatography were performed less often in patients undergoing spEE-CDCD reconstruction (p < 0.05). The technique of a spatulated end-to-end bile duct reconstruction provides a significant improvement in lowering biliary complication rates in liver transplant patients. Despite the modest number of cases in this study this technique shows promise and has become the technique of choice in our institution.     

同种原位肝移植术后并发症的防治体会

目的 探讨同种原位肝移植术后并发症发生的常见原因与预防及处理。方法 回顾性分析我科近一年来所施行的18例原位肝移植病人术后并发症发生的种类及数量,以及诊治处理方法,以探讨成功及失败原因,结果 18例肝移植病人中,原发病为终末期乙肝肝硬变13例,造型性弥漫性肝内胆管囊性扩张2例,布－加氏综合征1例,原发性肝癌2例,术后发生并发症15例次,含因凝血功能紊乱致术后腹腔内继发性出血3例,术前腹水感染未能控制致术后腹水严重感染1例,激素用量过大致应激性溃疡出血、穿孔1例,胆瘘1例,肺部感染4例,口腔弥漫性溃疡3例,肠道霉菌感染2例,手术死亡3例,分别为肺部曲霉菌感染,应激性溃疡穿孔及腹水感染所致。术后5个在肝癌复发死亡1例,现仍存活14例,4例已存活1年以上。结论 我国肝移植病人适应证以终末期,乙肝肝硬化为主,这类病人肝功不良,凝血障碍,围手术期凝血功能的纠正甚为重要,同时这类病人多存在营养不良,免疫功能低下,应重视围手术期感染的控制及营养支持,手术技术的完善是预防肝移植后血管并发症的关键。     

原位肝移植术后胆管并发症的预防与处理

目的 探讨原位肝移植术后胆管并发症的原因及防治。方法 2000年5月至2002年1月38例原位肝移植的临床资料进行回顾性研究。结果 本组38例病人术后共发生胆管并发症9例（9/38，24%）。其中单纯胆瘘4例，胆管空肠吻合口狭窄，肝内胆管结石，胆管狭窄合并胆泥形成，胆瘘继发胆管狭窄，胆管狭窄合并肝内胆汁瘤各1例。此9例中2例死于严重感染，7例痊愈。结论 原位肝移植术后胆管并发症病因复杂，后果严重。首先应该注重预防，并做到早期诊断。逆行性胰胆管造影术（endoscopic retrograde cholangiopanreatography,ERCP）和经皮经肝胆管造影术（percutaneous tran-shepatic cholangiography,PTC）等辅助性介入治疗手段应受到重视。     

The incidence and management of biliary complications following liver transplantation in children

Biliary complications following liver transplantation are a cause of significant morbidity and mortality. During the period 1988–1993 ten cases of biliary complications occurred after 98 transplantations in 78 children. The complications were four bile leaks, three intrahepatic biliary strictures (one with recurrent cholangitis), two anastomotic biliary strictures (one with recurrent cholangitis) and one recurrent cholangitis. All leaks occurred within 6 weeks of transplantation whereas all strictures and cholangitic episodes occurred after 3 months. Two biliary complications (20%) — one intrahepatic and one anastomotic stricture — developed secondary to hepatic artery thrombosis. The incidence of biliary complications was 13.2% with whole liver grafts as compared to 6.7% with partial liver grafts and it was 4.3% with duct-to-duct anastomosis as compared to 12.0% with Roux-en-Y hepatico-jejunostomy. Seven children required intervention for management of biliary complications and three were managed conservatively. There were no deaths related to the biliary complications.     

Duct-to-duct biliary reconstruction in living donor liver transplantation utilizing right lobe graft

OBJECTIVE: To assess the feasibility and safety of duct-to-duct biliary anastomosis for living donor liver transplantation (LDLT) utilizing the right lobe. SUMMARY BACKGROUND DATA: Biliary tract complications remain one of the most serious problems after liver transplantation. Roux-en-Y hepaticojejunostomy has been a standard procedure for biliary reconstruction in LDLT with a partial hepatic graft. However, end-to-end choledochocholedochostomy is the technique of choice for biliary reconstruction and yields a more physiologic bilioenteric continuity than can be achieved with Roux-en-Y hepaticojejunostomy. The authors performed right lobe LDLT with end-to-end duct-to-duct biliary anastomosis, and this study assessed retrospectively the relation between the manner of reconstruction and complications. METHODS: Between July 1999 and December 2000, 51 patients (11-67 years of age) underwent 52 right lobe LDLTs with duct-to-duct biliary reconstruction and remained alive more than 1 month after their transplantation. Interrupted biliary anastomosis was performed for 24 transplants and the continuous procedure was used for 28. A biliary tube was inserted downward into the common bile ducts through the recipient's cystic duct in 16 transplants (cystic drainage), or a biliary stent tube was pushed upward into the anastomosis through the cystic duct in four transplants (cystic stent), or upward into the anastomosis through the wall of the common bile duct in 31 transplants (external stent). RESULTS: Biliary anastomotic procedures consisted of 34 single end-to-end anastomoses, 11 double end-to-end anastomoses, and 7 single anastomoses for double hepatic ducts. Overall, 5 patients developed leakage (9.6%) and 12 patients suffered stricture (23.0%). For biliary anastomosis with interrupted suture, the incidence of stricture was significantly higher in the cystic drainage group (53.3%, 8/15) than in the stent group consisting of cystic stent and external stent (0%, 0/8). While the respective incidences of leakage and stricture were 20% and 53.3% for intermittent suture with a cystic drainage tube (n = 15), they were 7.7% and 15.4% for a continuous suture with an external stent (n = 26). There was a significant difference in the incidence of stricture. CONCLUSIONS: Duct-to-duct reconstruction with continuous suture combined with an external stent represents a useful technique for LDLT utilizing the right lobe, but biliary complications remain significant.     

Effects of liver transplantation on the nutritional status of patients with cystic fibrosis.

The long-term effects of liver transplantation on nutritional status, body composition and pulmonary function in patients with liver disease associated with cystic fibrosis (CF) are poorly defined. We studied 15 patients with CF-associated biliary cirrhosis and severe portal hypertension. Seven underwent liver transplantation (age: 14.8 +/- 6.2 years), and eight were treated conservatively (age: 15.9 +/- 6.7 years). All patients were evaluated at baseline and thereafter yearly for a median duration of 5 years. During follow-up, transplanted patients gained weight and showed a significant increment in body mass index (P < 0.004), whereas patients without transplantation remained stable (P = 0.063). Baseline bone mineral content (dual energy X-ray absorptiometry scan) was lower than normal in all patients (more in transplanted patients) and increased in transplanted patients (P < 0.05), but not in patients without transplantation. In both groups percent body fat did not change, whereas fat free mass increased only in the transplant group (P = 0.06) (P < 0.03 versus nontransplanted patients). Only in transplanted patients' plasma concentrations of vitamin E and A increased (P < 0.05 versus nontransplanted patients). Forced espiratory volume in 1 s and forced vital capacity showed similar deterioration in transplanted and in nontransplanted patients. Liver transplantation is associated with long-term beneficial effects on the nutritional status of CF patients and seems to favor bone mineralization.     

Liver transplantation in infants

PURPOSE: In view of the earlier reports that children below 1 year of age constitute a high-risk group for liver transplantation, the authors reviewed their experience in performing orthotopic liver transplantation in this age group. METHODS: The records of 9 children aged less than 1 year who underwent 6 living-related liver transplants and 3 reduced-size liver transplants between December 1993 and June 1997 were reviewed. RESULTS: Five reexplorations were required for 3 children who had 1 or more of the following early complications: bleeding from hepatic vein to inferior vena cava anastomosis (n = 1), right hepatic vein stump bleeding (n = 1), intraabdominal hematoma (n = 2), jejuno-jejunostomy leakage (n = 1), and colonic perforation (n = 1). Late complications include stricture at the biliary-enteric anastomosis requiring percutaneous balloon dilatation (n = 3) and hepatitis of undetermined etiology requiring retransplantation (n = 1). There was no hepatic artery thrombosis despite the small arteries available for anastomosis. Follow-up ranged from 19 to 61 months (mean, 40 months). Patient survival rate was 100%, and graft survival with good liver function was 89%. All living donors, 2 fathers and 4 mothers, are well. CONCLUSIONS: Liver transplantation in infants less than 1 year of age is technically demanding but feasible and still can be performed with a good outcome. Age alone (under 1 year) should not be considered as a contraindication for liver transplantation.     

30例原位肝移植手术临床分析

目的总结原位肝移植手术的临床经验,探讨提高肝移植手术效果的措施。方法回顾分析2003年12月~2006年3月30例原位肝移植患者的临床资料,均采用同种异体(尸体供肝)原位全肝移植,其中经典式24例,背驮式6例。结果30例手术全部成功,供肝热缺血时间平均4.5 m in,冷缺血时间5 h。围术期死亡3例。与手术相关主要并发症有:腹腔内出血4例,门静脉狭窄2例,胆道吻合口狭窄1例、胰漏1例、胸腔积液5例。27例获随访3~30个月,1例术后3月死于胆道铸型综合征并感染,肝癌复发2例。结论确保供肝质量是肝移植成功的前提,良好的血管和胆管重建技术是肝移植手术成功的关键,专业化的围手术期处理可有效地减少并发症的发生。