Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation

Kyoden Y, Tamura S, Sugawara Y, Matsui Y, Togashi J, Kaneko J, Kokudo N, Makuuchi M. Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation.
Clin Transplant 2010: 24: 535–542.
© 2009 John Wiley & Sons A/S. Abstract: Background: There are few detailed reports of biliary complications in a large adult living donor liver transplantation (LDLT) series. Patient and methods: Biliary complications, treatment modalities, and outcomes in these patients were retrospectively analyzed in 310 adult LDLT. Results: One patient underwent retransplantation. Duct‐to‐duct anastomosis was primarily performed in 223 patients (72%). During the observation period (median 43 months), biliary complications were observed in 111 patients (36%); 53 patients (17%) had bile leakage, 70 patients (23%) had bile duct stenosis, and 12 patients (4%) had bile leakage followed by stenosis. A biliary anastomotic stent tube was placed in 266 patients (86%) at the time of transplantation. Univariate analysis of various clinical factors revealed duct‐to‐duct anastomosis as the single significant risk factor (p = 0.009) for biliary complications. The three‐yr and five‐yr overall patient survival rates were 88% and 85% in those with biliary complications, and 85% and 83%, respectively, in those without biliary complications (p = 0.59). Conclusion: Biliary complications are a major cause of morbidity following LDLT. Duct‐to‐duct anastomosis carried a higher risk for bile duct stenosis. With appropriate management, however, there was little influence on overall survival.     

Biliary‐enteric bypass in unresectable malignant hilar biliary obstruction: Kwong Wah Hospital experience

Objective : To evaluate the efficacy of biliary‐enteric bypass in the palliation of malignant hilar biliary obstruction. Materials and Methods : Records of 19 patients from 1995 to 1998 were reviewed. There were 13 patients with cholangiocarcinoma and 6 patients with carcinoma of the gallbladder. Single biliary‐enteric bypass had been performed in 13 of the patients; the rest had more than one biliary‐enteric anastomosis. Results : The 30‐day mortality was 21% (4/19 patients). Bile leakage occurred in 2 patients, leading, in both, to fatality. Excluding the 30‐day mortality, the median survival of patients with carcinoma of the gallbladder and cholangiocarcinoma was 116 days (43–200) and 202 days (47–1207), respectively. The mean hospital stay was 31 days (13–59) and all patients were discharged with their symptoms relieved and a drop in bilirubin of at least two‐thirds their pre‐operative level. The late complication rate was 26.7% (4/15 patients). Conclusion : Biliary‐enteric bypass is effective in the palliation of symptoms of patients suffering from unresectable hilar biliary obstruction, although it carries considerable mortality and morbidity. Stenting, rather than surgery, should be considered for patients with unresectable gallbladder cancer.      

医源性晚期胆管狭窄的起因和处理

本组医源性晚期胆管狭窄的７６例病例中６３例,是胆囊切除或胆道探查手术损伤所致,其中曾行一次或多次胆管修复无效者３８例,隐性胆管损作远期发生狭窄１４例,胆道探查“Ｔ”管引流后期胆管狭窄１４例,胆道探查“Ｔ”管引流后期胆管狭窄１１例;因胆肠吻合术的适应证选择不当或吻合口狭窄１３例。胆管损伤的早期修复的关键是根据不同情况选择恰当的修复术式,缝合技术准确精细,吻合口宽大,无张力,避免胆漏和感染,晚期胆管狭     

梗阻性胆管损伤一期修复时机的选择

Objective To observe the pathological changes of tissues of the injured bile duct, and to provide theoretical basis for bile duct repair. Methods Dog models of obstructive biliary injury were established.Sixty dogs were equally divided into five groups according to the duration of biliary obstruction: biliary obstruction for 5 days (BDL5 group), 10 days (BDL10 group), 15 days (BDL15 group), 20 days (BDL20 group) and 30 days (BDL30 group). The morphological and pathological changes of bile duct and local tissues were observed, and biliary-enteric Roux-en-Y anastomosis was applied to repair the injured bile duct and postoperative complications were observed. All data were analyzed by LSD test, independent sample t test, one-way analysis of variance and chi-square test. Results Proximal bile duct rapidly expanded as the pressure increased in the early stage, and the bile duct expanded to ( 15.6 ± 1.8)mm in the BDL10 group. The expansion rate decreased in the later stage,and the bile duct expanded to (18.9 ± 1.9)mm in the B DL15 group. Acute inflammation was observed in injured local tissues. The acute inflammation was severe in the BDL5 group with white blood cell count of 54 ± 6, and the acute inflammation was relatively mild in the BDL15 group with white blood cell count of 42 ± 7. There was a significant difference between the BDL5 group and BDL15 group in the degree of acute inflammation (t =4. 688,P ＜ 0. 05). The content of the collagen was increased in the injured bile duct as time passed by. Bile duct repair was successfully performed on 57 dogs. Ten dogs ( three in the BDL5 group, four in the BDL10 group, one in the BDL15 group, one in the BDL20 group and one in the BDL30 group) died of bile leakage after the operation. The incidences of bile leakage was 30% (7/23) within 10 days and 9% (3/34) beyond 10 days, with a significant difference between the two groups (x2 =4.429, P＜0.05). Conclusion Ten days after obstructive biliary injury,an obvious reduction of bile duct expansion and edema of the bile duct is observed, the difficulty of the operation is reduced and the incidence of bile leakage is low, so 10 days after the incidence of obstructive biliary injury is the proper timing for the surgical repair.     

局部胆管内压大小及持续时间对犬胆管壁的影响

目的探讨局部胆管内压大小及持续时间对犬胆管壁的影响。方法设计并自制一内置入式胆管扩张器,体外测试扩张气囊内压力与注水容积及囊径的关系。将20只杂交犬随机分为五组,A组为假手术组仅在胆总管内放置胆管扩张器;B、C组分别向扩张气囊内注水0.1ml、0.2ml（球囊压力分别为0.24Kpa、0.58Kpa）扩张胆总管10min后抽空气囊并留置胆管扩张器作胆汁引流;D、E组分别向扩张气囊内注水0.1ml、0.2ml扩张胆总管后,不抽空气囊并留置作胆汁引流。各组分别术后7天再次剖腹。观察各组扩张前后血清总胆红素（TB）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）值及胆管直径（BD）变化、胆管壁及肝组织学改变。结果与A组比较,C组扩张后BD增宽（P〈0.05）。D组扩张后BD显著增宽（P〈0.01）,E组扩张后TB、ALT、AST均增高（P〈0.01）。A、B组胆管壁组织学无明显变化,C组胆管壁粘膜充血水肿,部分粘膜脱落,D组胆管直径增粗及胆管壁增厚,E组胆管壁部分坏死,与网膜或十二指肠粘连。结论局部胆管内压大小及持续时间对犬胆管壁的影响存在双向互变关系,正常胆管壁在一定的时间内可承受一定的局部胆管内压而不致发生胆管壁的病理变化,适宜的局部胆管内压可引起局部胆管及其上游胆管壁扩张,反之,胆管壁可出现破坏性改变。     

Adjuvant therapies using biliary stenting for malignant biliary obstruction

The aim of this study was to analyze the patency of expandable metallic stents in malignant biliary obstruction and to evaluate the efficacy of adjuvant therapy accompanied by biliary stenting. We analyzed 29 patients in whom bile duct stenting was performed for malignant biliary obstruction. Their types of disease were: hilar ductal carcinoma (n = 8), gallbladder carcinoma (n = 11), and pancreatic carcinoma (n = 10). Initially, 46 expandable metallic stents were placed in 29 patients. In 23 of the 29 patients, adjuvant therapy was administered. Seventeen patients underwent radiotherapy, and 16 patients received various systemic chemotherapies. In principle, hyperthermia was performed twice a week, simultaneously with radiotherapy. Patient survival and the probability of stent patency were calculated using actuarial life table analysis. There was no significant difference in stent patency among the patients according to type of disease. Hyperthermia did not influence the stent patency rate. The median stent patency time was significantly greater in the chemo-radiation group than in the no-adjuvant therapy group: 182 days versus 68 days, respectively (P = 0.017). Moreover, a significant increase was seen in the median survival time in the chemo-radiation group: 261 days versus 109 days (P = 0.0337). Complications occurred in 9 patients (31.0%). Stent occlusion occurred in 6 patients (20.7%), with all of these patients managed successfully using a transhepatically placed new expandable metallic stent, employing the stent-in-stent method. Stent migration occurred in 2 patients after radiotherapy. Adjuvant therapies such as radiotherapy and systemic chemotherapy, in combination with stent insertion, resulted in an increase in the patency period of expandable metallic stents and in increased patient survival time. Received: August 18, 2000 / Accepted: December 1, 2000     

Comparative analysis of iatrogenic injury of biliary tract in laparotomic and laparoscopic cholecystectomy

Background

Iatrogenic injury to the bile ducts is the most feared complication of cholecystectomy and several are the possibilities to occur.

Aim

To compare the cases of iatrogenic lesions of the biliary tract occurring in conventional and laparoscopic cholecystectomy, assessing the likely causal factors, complications and postoperative follow-up.

Methods

Retrospective cohort study with analysis of records of patients undergoing conventional and laparoscopic cholecystectomy. All the patients were analyzed in two years. The only criterion for inclusion was to be operative bile duct injury, regardless of location or time of diagnosis. There were no exclusion criteria. Epidemiological data of patients, time of diagnosis of the lesion and its location were analyzed.

Results

Total of 515 patients with gallstones was operated, 320 (62.1 %) by laparotomy cholecystectomy and 195 by laparoscopic approach. The age of patients with bile duct injury ranged from 29-70 years. Among those who underwent laparotomy cholecystectomy, four cases were diagnosed (1.25 %) with lesions, corresponding to 0.77 % of the total patients. No patient had iatrogenic interventions with laparoscopic surgery.

Conclusion

Laparoscopic cholecystectomy compared to laparotomy, had a lower rate of bile duct injury.     

良性胆管狭窄形成机制的研究

目的 探讨良性胆管狭窄的形成机制。方法 用28只犬建立犬胆总管损伤修复的动物模型,分别于术后3d、1周、3周、3月、6月取材行光镜、电镜观察及免疫纵化观察巨噬细胞、转化生长因子（TGF-β1）、平滑肌肌动蛋白（α-SMA）在胆管愈合过程不同时期组织中的表达强度、阳性细胞数和组织分布。结果 光镜及电镜显示:在整个胆管修复过程中炎性渗出期较长,胆道粘膜上皮愈合较慢,瘢痕组织细胞持续增生活跃,细胞外基质过度沉积,胶原纤维排列致密杂乱。肌成纤维细胞（MFB）功能活跃,持续存在于整个愈合过程中。免疫组化:巨噬细胞、TGF-β1、α-SMA在胆管愈合过程中表达较强,且持续较长时间。MΦ阳性主要表达于胆道粘膜下固有层;TGF-β1主要表达于肉芽组织、成纤维细胞、MΦ由及血管内皮细胞胞浆和细胞膜;α-SMA表达于MFB胞浆、平滑肌组织。MΦ、TGF-β1及α-SMA的表达呈正相关。结论 ①胆管愈合方式属于过度愈合。②肌成纤维细胞功能活跃,持续存在,是导致胆管瘢痕性挛缩的重要原因。③MΦ、TGF-β1及α-SMA高表达是造成胆管愈合过程中成纤维细胞增殖旺盛、细胞外基质过度沉积、胆管瘢痕性挛缩的重要因素。     

“Inside‐Out” PEGylation of Bovine β‐Cross‐Linked Hemoglobin

The development of a blood substitute is urgent due to blood shortages and potential communicable diseases. A novel method, inside‐out PEGylation, has been used here to conjugate a multiarm maleimide‐PEG (Mal‐PEG) to β‐cross‐linked (βXL‐Hb) hemoglobin (Hb) tetramers through the Cys β93 residues. This method produces a polymer with a single PEG backbone that is surrounded by multiple proteins, rather than coating a single protein with multiple PEG chains. Electrophoresis under denaturing conditions showed a large molecular weight species. Gel filtration chromatography and analytical ultracentrifugation determined the most prevalent species had three βXL‐Hb to one Mal‐PEG. Thermal denaturation studies showed that the cross‐linked and PEGylated species were more stable than native Hb. Cross‐linking under oxy‐conditions produced a high oxygen affinity Hb species (P₅₀ = 9.18 Torr), but the oxygen affinity was not significantly altered by PEGylation (P₅₀ = 9.67 Torr). Inside‐out PEGylation can be used to produce a hemoglobin‐based oxygen carrier and potentially for other multiprotein complexes.     

Endoscopic retrograde biliary drainage for posttraumatic intrapancreatic biliary stenosis in a child

Bile duct injury caused by blunt abdominal trauma is rare and usually associated with liver parenchymal injury. The authors report the case of a 15-year-old boy with jaundice caused by a posttraumatic isolated common bile duct stricture without associated liver injury. Endoscopic retrograde biliary drainage (ERBD) was performed and the jaundice disappeared 2 months after drainage commenced. Although restenosis and mild jaundice was revealed 2 years after injury, ERBD can be a first-line minimally invasive treatment of pediatric posttraumatic biliary stricture.     

Peroral cholangioscopy for the diagnosis and treatment of biliary diseases

Peroral cholangioscopy with duodenoscopic assistance can allow direct visualization of the bile duct. Several clinical studies suggest the utility of peroral cholangioscopy for the management of various bile duct lesions. Although direct visual observation may be a useful adjunct to endoscopic retro-grade cholangiopancreatography (ERCP) for distinguishing malignant from benign bile duct lesions, the assessment of diagnostic accuracy needs further controlled clinical studies. Intracorporeal lithotripsy with the use of a peroral cholangioscope may be a safe and effective method for difficult-to-treat bile duct stones, including intrahepatic stones. At present, however, the fragility of the fiberscope equipment and technical difficulties hold back its popularity. Preliminary data obtained by using a new videoscope, which provides excellent quality images, are encouraging. Furthermore, it is expected that this videoscope will have longer durability of optical images and better manipulation than previous fiberscopes.     

Prediction of biliary anastomotic stricture after deceased donor liver transplantation: the impact of platelet counts – a retrospective study

Biliary stricture is a common cause of morbidity after liver transplantation (LT). This study aimed to determine the risk factors for post‐transplant biliary anastomotic strictures (BAS), focusing on perioperative platelet counts. We enrolled 771 consecutive recipients who underwent ABO‐identical/compatible deceased donor LT with duct‐to‐duct biliary reconstruction from January 2000 to June 2012. BAS was identified in 142 cases. The median time for stricture development was 176 days. Preoperative and postoperative platelet counts within 5 days after LT were significantly lower in patients with BAS than those without BAS. Using cutoff values acquired by the receiver operating characteristic curve analysis, persistent postoperative thrombocytopenia was defined as platelet counts <41 × 1000/μl and <53 × 1000/μl on postoperative day (POD) 3 and POD 5, respectively. Multivariate analysis indicated persistent postoperative thrombocytopenia (OR = 2.38) was the only independent risk factor for BAS. No significant associations were observed in terms of donor and surgical factors. Multivariate analysis demonstrated estimated blood loss (OR = 1.01, per 100 ml) was an independent contributing factor for persistent postoperative thrombocytopenia. We demonstrated low platelet count was associated with progression of post‐transplant BAS. Minimizing intraoperative blood loss potentially contributes to maintain post‐transplant platelet count, which may reduce incidence of BAS.     

复杂性肝内胆管结石的外科治疗

目的　总结复杂性肝内胆管结石的外科治疗方法及效果。 方法　 总结分析１９９２ ～１９９８ 年外科治疗复杂性肝内多段胆管结石并多处胆管狭窄３５ 例的手术方法,总结显露与切开肝内狭窄段胆管、取出结石、解除狭窄的经验和体会。 结果　３５ 例无手术死亡,术后近期并发感染、胆漏、肝功能不全或消化道出血共７ 例,均治愈;残留结石９ 例,术后经胆道镜取净结石７ 例。随访６ 个月至５ 年６ 个月２４ 例,优良２１ 例（８８ ％ ） ,好转２ 例（８ ％ ） ,无效１ 例（４ ％ ） 。 结论　复杂肝内胆管结石外科治疗的关键是显露和切开肝内各叶段胆管的狭窄段,取出结石、建立通畅的胆流通道。经肝门区或肝方叶可以显露和切开肝门胆管、左右肝管和左内叶、右前叶胆管,经肝膈面切开肝实质进路,可以显露和切开右肝内各叶段胆管。     

梗阻性胆管损伤一期修复时机的选择

目的 观察胆管梗阻性损伤后的病理学改变,为胆管修复手术时机的选择提供理论依据.方法 建立家犬梗阻性胆管损伤模型,将60只家犬按照梗阻时间的长短分为胆管梗阻5 d组(BDL5组),胆管梗阻10 d组(BDL10组),胆管梗阻15 d组(BDL15组),胆管梗阻20 d组(BDL20组)和胆管梗阻30 d组(BDL30组)...     

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目的 分析胆肠吻合术治疗肝内胆管结石并胆道狭窄的选择和疗效。方法 对１９９１年９月至１９９８年１２月６９例行胆肠吻合术的肝内胆管结石并胆道狭窄病例进行总结,包括临床表现、结石部位、狭窄情况、手术方式和治疗效果等。结果 胆管狭窄主要位于１￣２级胆管内。５１例（７３．９％）行肝胆管空肠Ｒｏｕｘ－ｅｎ－Ｙ吻合术,１８例（２６．１％）采用胆总管十二指肠吻合术,随访结果表明,肝胆管空肠Ｒｏｕｘ－ｅｎ－Ｙ吻合