Orthotopic liver transplantation for patients with Klatskin tumor

BACKGROUND; It is not certain whether Klatskin tumor should be a routine indication for orthotopic liver trans- plantation (OLT). This study was to summarize the indi- cation and value of orthotopic liver transplantation for pa- tients with Klatskin tumor. METHODS; Forty patients with Klatskin tumors including 5 patients who had had liver transplantation ( LTx) and 35 patients who had not undergone LTx ( WLTx) from Janu- ary 1992 to December 2003 were analyzed retrospectively. Their TNM stages were comparable in both groups. In the LTx group, 4 patients had Klatskin tumor including recur- rent tumor after resection ( 1 ), and 1 cancerization from Carolis disease. Biliary duct anastomosis was made by Roux-en-Y choledochojejunostomy in 2, and end-to-end choledochocholedochostomy (C-C) in 3. RESULTS: In the LTx group, the total resection rate and radical resection rate were both 100%. Four patients have been surviving for 48, 38, 21 and 5 months, respectively, except one died from bile leakage at day 40 after transplan- tation. All 4 survivors enjoyed good life without tumors at local and distant sites, even though 2 of these patients de- veloped biliary stricture, which was soon resolved by radio- logical intervention. The 1-,3-year survival rates were both 80% in this group. The total resection rate and radical re- section rate in the WLTx group were 63.0% ( 17/27) and 40.7% (11/27 ) and, the 1-, 3-, 5-year survival rates were 32.2%, 8.0%, 0%, respectively. There were significant differences between the two groups in radical resection rates and survival rates( P =0.016).CONCLUSIONS: OLT is a good choice for patients with unresectable Klatskin tumor by routine modalities. The prognosis of patients undergoing OLT is encouraging.

Laparoscopic step 1 ALPPS with microwave transection of theliver for Klatskin tumors:Is it worthwhile?

To the Editor：Associating liver partition and portal vein ligation for stagedhepatectomy （ALPPS） was introduced in 2007 [1]. This techniqueis now used worldwide and has a wide spectrum of indications.However, scientific debate and un-regulated surgical experimentationconcerning the application of this technique led the surgeons to organize the first Consensus Meeting [2] to build a scientificconsensus. One of the most controversial indications to ALPPS isits application for Klatskin tumors. The aim of this letter is to analyzethe critical aspects of laparoscopic microwave ALPPS for radicalsurgical treatment of Klatskin tumors.

Outcome of surgical resection in Klatskin tumors

Cholangiocarcinomas are the second most frequent primary hepatic malignancy,and make up from 5% to 30% of malignant hepatic tumours.Hilar cholangiocarcinoma(HCC) is the most common type,and accounts for approximately 60% to 67% of all cholangiocarcinoma cases.There is not a staging system that permits us to compare all series and extract some conclusions to increase the long-survival rate in this dismal disease.Neither the extension of resection,according to the sort of HCC,is a closed topic.Some authors defend limited resection(mesohepatectomy with S1,S1 plus S4b-S5,local excision for papillary tumours,etc.) while others insist in the compulsoriness of an extended hepatic resection with portal vein bifurcation removed to reach cure.As there is not an ideal adjuvant therapy,R1 resection can be justified to prolong the survival rate.Morbidity and mortality rates changed along the last decade,but variability is the rule,with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%,respectively.Conclusion:Surgical resection continues to be the main treatment of HCC.Negative resection margins achieved with major hepatic resections are associated with improved outcome.Preresectional management with biliary drainage,portal vein embolization and staging laparoscopy should be considered in selected patients.Additional evidence is needed to fully define the role of orthotopic liver transplant.Portal and lymph node involvement worsen the prognosis and long-term survival,and surgery is the only option that can lengthen it.Improvements in adjuvant therapy are essential for improving long-term outcome.Furthermore,the lack of effective chemotherapy drugs and radiotherapy approaches leads us to can consider R1 resection as an option,because operated patients have a longer survival rate than those who not undergo surgery.

Placement of ^(125)I seed strands and stents for a type Ⅳ Klatskin tumor

Herein,we report a new technique that consists of placing two 125 I seed strands and two stents in the right and left intrahepatic bile ducts for the treatment of hilar cholangiocarcinoma.A 75-year-old man presented with jaundice and was diagnosed with Bismuth type Ⅳ Klatskin tumor.Abdominal computed tomography(CT) showed intrahepatic and extrahepatic bile ductdilatation and a soft tissue mass in the hepatic hilum.Because curative surgical resection was not possible,we placed 125 I seed strands and stents in the right and left intrahepatic bile ducts.Three months later,abdominal CT showed less intrahepatic and extrahepatic bile duct dilatation than before the procedure.This technique was feasible and could be considered for the treatment of patients with Bismuth type Ⅳ tumors.

Klatskin tumor treated by inter-disciplinary therapies including stereotactic radiotherapy: A case report

In view of the poor prognosis of patients with cholangiocarcinoma (CCC), there is a need for new therapeutic strategies. Inter-disciplinary therapy seems to be most promising. Radiotherapy is an effective alternative to surgery for hilar CCC (Klatskin tumors) if an adequate radiation dose can be delivered to the liver hilus. Here,we describe a patient for whom we used a stereotactic radiotherapy technique in the context of an inter-disciplinary treatment concept. We report a 45-year-old patient with a locally advanced Klatskin tumor. Explorative laparotomy showed that the tumor was not resectable. A metallic stent was implanted and the patient was treated by stereotactic radiotherapy using a body frame. A total dose of 48 Gy (3x4 Gy/wk) was administered. Therapy was well tolerated. After 32 mo, local tumor recurrence and a chest wall metastasis developed and were controlled by radio-chemotherapy. After more than 56 mo with a good quality of life, the patient died of advanced neoplastic disease. Stereotactic radiotherapy led to a long-term survival of this patient with a locally advanced Klatskin tumor. In the context of inter-disciplinary treatment concepts, this radiotherapy technique is a promising choice of treatment for patients with hilar CCC.

Colonic metastasis of Klatskin tumor:Case report and discussion of the current literature

We report the case of a 65-year old male patient who initially presented with recurrent episodes of upper abdominal pain, lack of appetite and weight loss.Abdominal ultrasound indicated enlarged intrahepatic bile ducts, abdominal CT scan and ERC were performed andbile duct carcinoma (Klatskin Type Ⅲ b)The tumor was located in the segments 2,3,4 and 1 withpossible invasion of the left intrahepatic portal vein. Both the segments 2 and 3 of the liver were atrophic and displayed a cholestatic bile duct system. Preoperatively an intraductal stent was placed in the left bile duct using ERC to drain the left hepatic lobe. A specimen of the ascites present preoperatively displayed no malignant cells. After evaluation of the preoperatively obtained data left hepatic resection was planned. Following laparotomy we found local peritoneal carcinosis in the ligamentum hepatoduodenale with lymphatic nodules that tested positive for cholangiocellular carcinoma in online pathological examination. In the course of further exploration of the abdomen a solid tumor was detected in the sigmoid colon. Regarding the advanced stage of the neoplasm it was decided to cancel hemihepatectomy and perform sigmoid resection only in order to guarantee uncomplicated intestinal passage. The sigmoid colon was removed by a typical resection technique with end-to-end anastomosis. Histological examination of the resected sigmoid revealed transmural manifestation of a malignant neoplastic process with both a tubular and a solid growth pattern in conformity with metastasis of a Klatskin tumor. The mucosal layer showed no neoplastic alteration. Peritoneal carcinosis is a common phenomenon in the dissemination pattern of advanced-stage Klatskin tumors, yet to our knowledge this is the first case of intramural colonic growth following peritoneal metastasis.

Optimal biliary drainage for inoperable Klatskin's tumor based on Bismuth type

AIM: To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin’s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage (ERBD), external percutaneous transhepatic biliary drainage (EPTBD) and internal biliary stenting via the PTBD tract (IPTBD). METHODS: The initial success rate, cumulative patency rate, and complication rate were compared retrospectively, according to the Bismuth type and ERBD, EPTBD, and IPTBD. Patency was defined as the duration for adequate initial bile drainage or to the point of the patient’s death associated with inadequate drainage. RESULTS: One hundred thirty-four patients (93 men, 41 women; 21 Bismuth type Ⅱ, 47 Ⅲ, 66 Ⅳ; 34 ERBD, 66 EPTBD, 34 IPTBD) were recruited. There were no differences in demographics among the groups. Adequate initial relief of jaundice was achieved in 91% of patients without a significant difference in the results among different procedures or Bismuth types. The cumulative patency rates for ERBD and IPTBD were better than those for EPTBD with Bismuth type Ⅲ. IPTBD provided an excellent response for Bismuth type Ⅳ. However, there was no difference in the patency rate among drainage procedures for Bismuth type Ⅱ. Procedure-related cholangitis occurred less frequently with EPTBD than with ERBD and IPTBD. CONCLUSION: ERBD is recommended as the first- line drainage procedure for the palliation of jaundice in patients with inoperable Klatskin’s tumor of Bismuth type Ⅱ or Ⅲ, but IPTBD is the best option for Bismuth type Ⅳ.

MACC1的表达与Klatskin瘤临床病理特征及预后的关系

目的 :探讨结肠癌转移相关基因1(MACC1)在Klats kin瘤中的表达情况及其与Klats kin瘤临床病理特征及预后的关系。方法:采用免疫组织化学染色,测定肿瘤组织和相应癌旁组织中MACC1蛋白的表达;采用实时荧光定量PCR方法,检测Klatskin肿瘤组织、癌旁组织和正常胆管组织中MACC1 mRNA的表达。分析MACC1的表达与临床病理特征及预后的关系。结果:肿瘤组织中MACC1蛋白的阳性表达率明显高于相应癌旁组织(P<0.05);肿瘤组织中MACC1 mRNA的表达明显高于癌旁组织和正常胆管组织(P<0.05)。Klatskin瘤组织中MACC1表达与肿瘤大小、复发、淋巴结转移有相关性(P<0.05)。MACC1表达阳性和阴性患者1年、3年、5年的总生存率,差异有统计学意义(P<0.05)。结论:MACC1在Klatskin瘤中呈现高表达,并与其肿瘤大小、复发、淋巴结转移有相关性,影响患者预后。

Klatskin瘤的超声诊断

目的：探讨Klatskin瘤的超声影像特点及早期诊断的临床价值。材料和方法：对12例经病理学证实为Klatskin瘤患者的临床及超声影像资料进行回顾性分析。结果：超声能够显示肝内胆管扩张、肝管内瘤体或肝门部肿块、肝叶萎缩及肝门肿大淋巴结等有关该病所具有的影像特征。结论：超声显像对该病的诊断及鉴别诊断有重要价值，早期诊断应得到重视。

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Klatskin瘤的外科治疗

目的 :分析 31例Klatskin瘤的治疗方法及生存时间。方法 :选择术前肝动脉及门静脉造影均未显示有血管包裹侵犯的31例Klatskin瘤患者行手术治疗。手术方式为限制性肝切除、胆管 -空肠Roux -en -Y吻合术及胆道支架放置。全组患者术后均行腔内或体外照射放疗。结果 :以标本切缘有无肿瘤细胞作为根治性切除或姑息性切除的标准。本组根治性切除 17例 ,姑息性切除 14例。总体平均术后生存期为 17个月。根治切除组平均术后生存期为 2 1个月 ,姑息性切除组为 12个月。本组1例患者术后已存活 6年余 ,至今无复发证据。 5例发生术后并发症 (16 % ) ,围手术死亡 2例 (6 % )。结论 :对无肝动脉及门静脉侵犯或远处转移的Klatskin瘤患者 ,积极手术治疗为主要手段 ,术后辅以放射治疗 ,可预防或延迟局部复发 。

二维及彩色多普勒超声诊断Klatskin's瘤的回顾性研究

目的应用二维及彩色多普勒超声对Klatskin's瘤作出客观评价。方法回顾性分析经临床或病理证实的256例Klatskin's瘤患者的超声影像学资料。结果超声发现梗阻性黄疸256例,准确率100%;明确诊断Klatskin's瘤223例,准确率87.1%;漏诊21例,占8.2%;误诊12例,占4.7%。同时,超声可以提供对Klatskin's瘤邻近肝实质、胆囊、肝动脉、门静脉的浸润程度以及肝门淋巴结转移情况,并且进一步对Klatskin's瘤进行Bismuth分型。结论超声是Klatskin's瘤术前检查的首选影像学方法,对指导临床制定手术治疗方案具重要应用价值。

Hilar cholangiocarcinoma with intratumoral calcification: A case report

This report describes a rare case of hilar cholangiocarcinoma with intratumoral calcification that mimicked hepatolithiasis. A 73-year-old man presented to a local hospital with a calcified lesion in the hepatic hilum. At first,hepatolithiasis was diagnosed,and he underwent endoscopic stone extraction via the transpapillary route. This treatment strategy failed due to biliary stricture. He was referred to our hospital,and further examination suggested the existence of cholangiocarcinoma. He underwent left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. Pathological examination revealed hilar cholangiocarcinoma with intratumoral calcification,while no stones were found. To the best of our knowledge,only one case of calcified hilar cholangiocarcinoma has been previously reported in the literature. Here,we report a rare case of calcified hilar cholangiocarcinoma and reveal its clinicopathologic features.

肝门胆管癌（Klatskin肿瘤）1例

病例：患者男,46岁,因“反复肝区不适2个月,消瘦、黄疸,解陶土色便5d”,于2003年6月11日收入上海海员医院。体检：全身情况尚好,皮肤和巩膜金黄色,浅表淋巴结不肿大,心肺无异常,腹软,肝脾未触及,肝区无压痛。B超、CT、MRI检查均示肝区胆管、左肝管扩张,胆囊不增大,疑为肝门胆管癌。实验室检查：白细胞5．8×10^9／L，红细胞3．52×10^12，L，血红蛋白108g／L，血小板233×10^9／L；尿胆红素＋＋；丙氨酸氨基转移酶（ALT）401U／L，天冬氨酸氨基转移酶（AST）333U／L，

Liver transplantation in the management of cholangiocarcinoma:Evolution and contemporary advances

Cholangiocarcinoma(CCA)is an aggressive malignancy arising from the biliary epithelium.It may occur at any location along the biliary tree with the perihilar area being the most common.Prognosis is poor with 5-year overall survival at less than 10%,typically due to unresectable disease at presentation.Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours,but is frequently not possible due to locally advanced disease.On the other hand,orthotopic liver transplantation(LT)allows for a radical and potentially curative resection for these patients,but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes.In patients with perihilar CCA,within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT,excellent results have been achieved in the last decades,resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience.However,in intrahepatic CCA,the role of LT remains controversial and owing to dismal previous results it is not an accepted indication.Nevertheless,more recent studies have demonstrated favourable results with LT in early intrahepatic CCA,indicating that,under defined criteria,its role may increase in the future.This review highlights the history and contemporary advances of LT in CCA,with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.

Pathogen detection in patients with perihilar cholangiocarcinoma:Implications for targeted perioperative antibiotic therapy

Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces the regenerative capacity of the remaining liver.Therefore,targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma(pCCC).Methods:Between December 1999 and December 2017,251 pCCC patients were treated in our center.In total,115 patients underwent a microbiological analysis.In addition to the characterization of the specific microorganisms and antibiotic resistance,we analyzed subgroups according to preoperative intervention.Results:Enterococci(87/254,34%)and Enterobacteria(65/254,26%)were the most frequently detected genera.In 43%(50/115)of patients,Enterococcus faecalis was found in the bile duct sample.Enterococcus faecium(29/115)and Escherichia coli(29/115)were detected in 25%of patients.In patients with percutaneous transhepatic biliary drainage(3/8,38%)or stents(24/79,30%),Enterococcus faecium was diagnosed most frequently(P<0.05).Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012(P<0.05).With regard to fungal colonization,the focus was on various Candida strains,but these strains generally lacked resistance.Conclusions:pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention.Specifically,targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection.In our cohort,the combination of meropenem and vancomycin represents an effective perioperative medical approach.

肝门部胆管癌淋巴结转移和神经丛浸润特点及清扫要点

肝门部胆管癌是胆道中最常见的恶性肿瘤,根治性手术是患者可能获得长期生存的唯一手段。本文简述了肝门部胆管癌发生淋巴结转移、神经丛侵犯的特点,回顾了国内外目前对淋巴结清扫、神经丛廓清的观点。分析表明,国内外观点普遍认可区域淋巴结清扫、神经丛廓清,但对淋巴结的扩大清扫尚存争议。

Endobiliary radiofrequency ablation for malignant biliary obstruction

BACKGROUND: The cornerstone of palliative treatment for inoperable extrahepatic cholangiocarcinoma is the relief of malignant biliary obstruction. The most commonly applied method is endoscopic stenting. However, the procedure can be complicated with stent obstruction. In this respect, endobiliary radiofrequency ablation may serve as an adjunctive tool for prolonging the stent patency. METHODS: Patients who underwent endoscopic retrograde cholangiopancreatography for differential diagnosis and/ or palliative treatment after the diagnosis of inoperable extrahepatic cholangiocarcinoma between March 2011 and January 2012 were analyzed. Those in whom endobiliary radiofrequency ablation and endoscopic stenting was successfully performed were included in the study. Technical details of the procedure, duration of stent patency, length of hospital stay, short-term morbidity and mortality rate were documented. RESULTS: Seventeen patients were analyzed, and 10 patients were included in the study. The morbidity and mortality rate within the first 30 days after the procedure was 20% and 0%, respectively. In 2 patients, mild pancreatitis occurred because of the endobiliary procedure. In 1 patient, endobiliary decompression could not be achieved, and therefore, percutaneous transhepatic biliary drainage was carried out. The median duration of stent patency in 9 patients with successful biliary decompression was 9 months (range 6-15). CONCLUSION: Endobiliary radiofrequency ablation seems to be safe and feasible as a palliative measure and may prolong the stent patency and overall survival in patients with malignant biliary obstruction due to inoperable extrahepatic cholangio-carcinoma.

肝门部胆管癌的临床肿瘤行为和外科治疗

目的研究肝门部胆管癌的临床肿瘤行为和外科治疗效果。方法回顾性分析1980年1月～2005年12月单机构收治的92例患者的临床表现、肿瘤行为和术后生存。结果肝门部胆管癌的主要临床症状为黄疸(97%,89例)、体重下降(39%,36例)、上腹不适(33%,30例)、上腹痛(27%,25例)。90%(83例)SGPT升高、37%(34例)低蛋白血症。Bismuth分型Ⅰ型29%(27例)、Ⅱ型22%(20例)、Ⅲ型16%(15例)、Ⅳ型33%(30例)。总体手术并发症33%(30例)、手术死亡率3%(3例)。39%(36例)切除、切缘阴性率53%(19例)。不能切除的患者62%(35例)局部广泛侵犯,39%侵犯大血管(22例),21%(12例)远处转移。总体中位生存8个月,手术切除后25个月、非切除性手术后5个月(P<0.0001)。结论局部侵犯(特别是大血管侵犯)和远处转移是肝门部胆管癌不能切除的主要原因。手术切除能够显著提高术后生存。

肝门部胆管癌手术治疗与生存状况的关系

目的探讨肝门部胆管癌(HCCA)患者联合肝切除的外科治疗效果与生存状况。方法选取2006年1月—2016年12月于天津市南开医院收治的93例联合肝切除术的HCCA患者作为研究对象,分析影响患者生存的因素。根据肝切除范围分为小范围组(小范围切除)和大范围组(大范围切除),比较两组患者的术后生存状况。采用多因素Cox风险回归模型分析影响患者生存的因素。结果病理结果表明44例(74.2%)患者达到R0切除标准,两组患者R0切除率比较,差异无统计学意义(P>0.05)。两组患者围手术期并发症发生率比较,差异无统计学意义(P>0.05)。两组患者术后1、3及5年生存率比较,差异无统计学意义(P>0.05)。多因素Cox风险回归分析模型结果表明,术前CA199>150 ku/L、肿瘤低分化、TNM分期为Ⅲ、Ⅳ期及镜下切缘阳性是患者术后预后不良的独立危险因素(P<0.05)。结论 HCCA患者联合肝切除术后的疗效并不理想,术前CA199>150 ku/L、肿瘤低分化、TNM分期为Ⅲ、Ⅳ期及镜下切缘阳性是患者术后预后不良的独立危险因素,而肝切除范围与其无关,在保证阴性切缘的前提下可考虑进行小范围肝切除。