Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

肝内周围型胆管细胞癌的CT诊断

目的:探讨肝内周围型胆管细胞癌(IHPCC)的CT特征,加深对IHPCC的认识。方法:回顾性分析经手术和病理证实的12例IHPCC的CT表现。结果:CT平扫12例均为类圆形或不规则形低密度灶,边界不清;病灶周围肝内胆管扩张5例;局部肝包膜回缩征象4例;增强扫描:动脉期与静脉期病灶无强化或轻度强化,延迟后病灶内部呈片状、分隔状或均匀强化。结论:IHPCC的CT表现有一定的特征性,对于与肝内其它常见病变的鉴别诊断具有重要价值。     

胆管癌误诊和漏诊的影像学分析

目的：分析胆管癌误诊和漏诊的原因，评价不同检查方法对肝门区胆管癌诊断的价值，提高胆管癌的影像学诊断和鉴别诊断水平。方法：收集31例临床和病理诊断为胆管癌的病例(ERCP检查31例，B超检查31例，25例CT检查，11例行MRCP检查)，回顾性分析不同检查方法的影像学表现。结果：31例中发生在肝门区的胆管癌25例。2例初次ERCP显示胆管内出血，再次行鼻胆管造影后诊断为胆管癌，4例合并有总胆管结石。6例为总胆管中下段癌。初次诊断准确性为90．3％。11例MRCP中9例显示病变，2例显示不满意，7例显示胆管或胆囊结石。25例CT中23例显示肝内胆管扩张，9例显示肝门区肿块，2例见后腹膜转移淋巴结，1例见肝内多发性转移瘤。12例初次诊断正确(48％)。B超检查23例提示肝内胆管扩张，6例提示总胆管结石，18例诊断为胆囊炎、胆囊结石，8例提示胆管占位(25．8％)。结论：良好的直接胆管造影是诊断胆管癌的金标准，MRCP可以在一定程度上准确显示病变的范围，是ERCP的良好补充，很大程度上取代了诊断性ERCP；CT诊断的关键在于显示扩张的胆管和梗阻的定位，肝门区梗阻多为胆管癌所致。多种影像检查方法的结合明显提高了诊断的准确性，对胆管癌治疗方案的选择有重要价值。     

肝外胆管癌的诊治分析

目的：探讨肝外胆管癌的诊断和治疗的体会。方法：回顾性总结手术治疗的32例肝外胆管癌的临床资料、手术方式、手术并发症及生存率，并复习相关文献资料。结果：本组病例获根冶性切除14例，姑息切除2例，胆道引流术16例；手术并发症10例(31.3％)，手术死亡1例(3．1％)。其中22例获定期随访，存活一年以上的有12例(12／22)，至今存活8例。结论:早期诊断、正确的评估、合理的术式选择能提高疗效。降低手术并发症及死亡率。     

bcl-2/bax mRNA在三氧化二砷体外诱导人胆管癌细胞株凋亡中的表达

目的 观察bcl-2、bax mRNA在三氧化二砷(As2O3)诱导人类胆管癌株QBC939、RBE细胞凋亡中的表达.方法 Rhodamine123染色检测线粒体膜通透性变化;逆转录-聚合酶链反应(RT-PCR)检测bcl-2、bax mRNA的表达.结果 As2O3干预,实验组Rhodamine123荧光染色强度较对照组明显减弱;凝胶成像检测bcl-2/β-actin mRNA A比值,QBC939、RBE细胞对照组分别为0.41±0.03、0.84±0.03;24 h实验组为0.01±0.01、0.43±0.02.bax/GAPDHmRNAA比值QBC939、RBE细胞对照组分别为0.21±0.01、0.42±0.04;24 h实验组为1.44±0.16、1.15±0.21,对照组与实验组比较差异均有统计学意义(P＜0.01).结论 As2O3可能增加胆管癌细胞株线粒体膜的通透性,下调bcl-2mRNA表达,上调bax mRNA的表达,可能启动了线粒体凋亡信号传导途径.     

Bismuth Ⅳ型肝门部胆管癌的外科治疗

目的探讨BismuthⅣ型肝门部胆管癌的外科治疗方法。方法对近5年来经手术和病理确诊的22例BismuthⅣ型肝门部胆管癌患者的临床资料进行回顾性分析。结果22例患者中,男13例,女9例,男女之比1.4∶1。常规手术方法治疗16例(常规手术治疗组),包括手术切除5例(31.3%),其中根治性切除2例,姑息切除3例;内或外引流术11例。经典式原位肝移植术6例(肝移植组)。常规手术方法治疗组1,2年累积生存率分别为32.1%,0;肝移植组除1例术后11个月死于慢性排异反应外,余均健康存活,现已分别存活28,19,17,12个月和9个月,未见肿瘤复发和转移,术后1,2年累积生存率分别为80.0%(4/5),50.0%(1/2)。两组生存率比较差异有显著性(P=0.041)。结论BismuthⅣ型肝门部胆管癌应行积极的外科治疗,其中根治性切除术是提高患者存活率的关健;常规手术无法根治切除者是原位肝移植的适应证,术后疗效满意。     

肝吸虫病合并胆管癌29例报告

目的 探讨肝吸虫病与胆管癌之间的病理机制及其临床诊治经验。方法 回顾性分析肝吸虫病合并胆管癌病人29例。结果男性21例，女性8例，平均年龄62．5岁，高分化腺癌13例(44．8％)，低分化腺癌16例(55．2％)。根治性肿瘤切除术21例(72．4％)，姑息性内引流术5例，剖腹探查活检术3例；生存10年者2例，5年者3例，3年者6例，1年者13例，6个月者4例，3个月者1例。结论 (1)肝吸虫感染、肝吸虫卵的沉积是诱发胆管上皮细胞增生、癌变的重要因素；(2)本病诊断有赖于病理，术中病理活检的广泛应用是提高其诊断符合率的有效措施；(3)治疗仍是以手术为主的综合治疗，能根治性切除则预后佳，不能根治者解决胆道梗阻也可延长生命。