Fine-needle aspiration biopsy of hepatic papillary cystadenocarcinoma in Caroli's disease.

A case of papillary adenocarcinoma arising in Caroli's disease (CD) in a 25-yr-old woman is reported. The diagnosis of malignancy was made by ultrasound-guided, fine-needle aspiration biopsy (FNAB). As there were no metastasis, a liver transplant was performed and the diagnosis was histologically confirmed. Only 22 cases of malignant transformation of CD have been reported to date, all among middle-aged subjects (mean age: 52 yr) of both sexes. Most of these reported cases (83%) were found to be bile duct adenocarcinomas with occasional reports of hepatocellular and undifferentiated carcinomas. Our case is the youngest reported to date and the first to be diagnosed cytologically.     

Malignant obstructive jaundice: treatment with external-beam and intracavitary radiotherapy

Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium192 (Ir192). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 "equivalent" cGy to his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir192 wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died--5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Mean survival time from initial laparotomy and bypass was 16.1 months, and from radiotherapy completion was 8.3 months. Evolution of radiation treatment techniques for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir192 intracavitary boost is well tolerated and provides significant palliation. Survival of these aggressively managed patients approaches that of patients with primarily resectable tumors.     

立体定向适形放疗治疗晚期胆管癌的疗效评价

目的 探讨立体定向适形放疗治疗晚期胆管癌的疗效。方法对 18例晚期胆管癌患者，采用立体定向适形放疗技术，总剂量平均为42．6Gy(32-48Gy)，分7-9次完成(隔天1次)，每次照射剂量为4-6Gy。结果治疗结束后，黄疸明显消退；CR 11例(61．1％)，PR5例(27．8％)，有效率为88．9％；随访中位生存期为15．4个月，1年生存率为61．5％(8/13)。结论 立体定向适形放射治疗晚期胆管癌，能改善患者的生存质量及预后。     

胆管癌的磁共振成像表现及其临床意义

目的：通过磁共振成像(MR)征象与手术对照分析，探讨胆管癌的MR特点。方法：27例患行常规轴位SE，12加权成像和呼吸门控FSE，12加权成像，并做冠状位：MRCP成像，所有患经手术和病理证实，分析病灶信号特征、形态、范围，并与术中所见进行比较。结果：16例肝门型胆管癌在磁共振成像上多呈放射状(89％)，术中所见病灶沿胆管浸润生长，且病灶范围比MRI所见大。所有胆管癌病灶在TIWI上均呈低信号(100％)，4例肝内胆管癌在T2WI上为混杂信号，11例肝门型胆管癌在，T2WI上呈等(61％)或稍高信号(39％)，2例壶腹癌在T2WI上呈低信号。在MRCP上所有病人表现为胆道梗阻。16例(89％)：MRCP分型与临床分型一致。结论：胆管癌在磁共振成像上有较特征性表现，且能提供病变准确部位，但对病变范围估计不足，MRCP用于肝门型胆管癌临床分型是可行的。     

左半肝切除在肝门部胆管癌手术治疗中的应用

目的探讨左半肝切除在肝门部胆管癌治疗中的可行性。方法回顾分析12例该手术方法的应用及治疗效果。结果Ⅰ型、Ⅱ型、Ⅲ型(ⅢA、ⅢB)肝门胆管癌均可通过左半肝切除，右肝管(Ⅰ级或Ⅱ级)、空肠Roue-Y吻合来达到根治的目的。本组切除率为52％。结论左半肝切除治疗肝门部胆管癌，简化了手术程序，减小了手术的创伤，提高了手术的切除率。     

COX-2和VEGF表达及其与胆管癌的相关性研究

目的:探讨环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)在胆管癌组织中的表达及其与胆管癌发生、发展及转移的关系。方法:运用免疫组织化学SP法研究COX-2和VEGF相关抗原在胆管癌组织中的表达。结果:43例胆管癌组织中COX-2和VEGF的表达阳性率分别为81.40%和76.74%,而二者在9例胆管结石病人的组织中均未见阳性表达;COX-2表达阳性率在胆管癌高、中分化组明显高于低分化组,转移阳性组明显高于转移阴性组,其差异均有显著性意义(P<0.05);VEGF的表达阳性率在胆管癌转移组明显高于未转移组,其差异有显著性意义(P<0.05);COX-2表达与VEGF表达呈正相关(r=0.727,P<0.01)。结论:COX-2和VEGF可能在胆管癌的发生、发展及转移过程中起着关键性作用,二者在血管生成过程中密切相关。     

Radiation therapy in cholangiocellular carcinomas

Cholangiocarcinoma can arise in all parts of the biliary tract and this has implications for therapy. Surgery is the mainstay of therapy however local relapse is a major problem. Therefore, adjuvant treatment with chemoradiotherapy was tested in trials. The SWOG-S0809 trial regimen of chemoradiotherapy which was tested in extrahepatic cholangiocarcinoma and in gallbladder cancer can currently be regarded as highest level of evidence for this indication. In contrast to adjuvant therapy where only conventionally fractionated radiotherapy plays a role, stereotactic body radiotherapy (SBRT) today has become a powerful alternative to chemoradiotherapy for definitive treatment due to the ability to administer higher doses of radiotherapy to improve local control. Sequential combinations with chemotherapy are also frequently employed. Nevertheless, in general cholangiocarcinoma is an orphan disease and future clinical trials will have to improve the available level of evidence.     

开腹胆道旁路手术治疗胆管癌的效果分析

目的：探讨开腹胆道旁路手术治疗胆管癌的效果。方法60例胆管癌患者，根据随机数字表法分为治疗组与对照组，各30例。对照组采用传统手术切除治疗，治疗组采用开腹胆道旁路手术治疗。结果所有患者都顺利完成手术，治疗组的术中出血量、术后住院时间、术后下床活动时间与术后肛门排气时间明显低于对照组（P＜0．05），而2组手术时间对比差异无统计学意义。2组术前的血清总胆红素值都呈现为高位状况，术后都明显降低（P＜0．05），同时术后治疗组的血清总胆红素值明显低于对照组（P＜0．05）；治疗组术后切口感染、肺部感染、胆漏、低氧血症、粘连性肠梗阻等并发症发生率明显低于对照组（P＜0．05）。术后随访6个月，治疗组复发率为0，对照组为16．7％，治疗组复发率明显低于对照组（P＜0．05）。结论开腹胆道旁路手术治疗胆管癌具有明显的微创优势，能促进胆功能的恢复，减少术后并发症的发生与远期复发率，值得推广应用。     

Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.