Risk factors and classifications of hilar cholangiocarcinoma

Cholangiocarcinoma is the second most common primary malignant tumor of the liver.Perihilar cholangiocarcinoma or Klatskin tumor represents more than 50% of all biliary tract cholangiocarcinomas.A wide range of risk factors have been identified among patients with Perihilar cholangiocarcinoma including advanced age,male gender,primary sclerosing cholangitis,choledochal cysts,cholelithiasis,cholecystitis,parasitic infection(Opisthorchis viverrini and Clonorchis sinensis),inflammatory bowel disease,alcoholic cirrhosis,nonalcoholic cirrhosis,chronic pancreatitis and metabolic syndrome.Various classifications have been used to describe the pathologic and radiologic appearance of cholangiocarcinoma.The three systems most commonly used to evaluate Perihilar cholangiocarcinoma are the Bismuth-Corlette(BC) system,the Memorial Sloan-Kettering Cancer Center and the TNM classification.The BC classification provides preoperative assessment of local spread.The Memorial Sloan-Kettering cancer center proposes a staging system according to three factors related to local tumor extent:the location and extent of bile duct involvement,the presence or absence of portal venous invasion,and the presence or absence of hepatic lobar atrophy.The TNM classification,besides the usual descriptors,tumor,node and metastases,provides additional information concerning the possibility for the residual tumor(R) and the histological grade(G).Recently,in 2011,a new consensus classification for the Perihilar cholangiocarcinoma had been published.The consensus was organised by the European Hepato-PancreatoBiliary Association which identified the need for a new staging system for this type of tumors.The classification includes information concerning biliary or vascular(portal or arterial) involvement,lymph node status or metastases,but also other essential aspects related to the surgical risk,such as remnant hepatic volume or the possibility of underlying disease.

Liver transplantation for hilar cholangiocarcinoma

The most appropriate treatment for Klatskin tumor(KT)with a curative intention is multimodal therapy based on achieving resection with tumour-free margins(R0resections)combined with other types of neoadjuvant or adjuvant treatment(the most important factor affecting KT survival is the possibility of R0 resections,achieving 5-year survival rate of 40%-50%).Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%.In irresectable non-disseminated KT patients,using liver transplantation without neoadjuvant treatment,the 5-year survival rate increase to 38%,reaching 50%survival in early stage.In selected cases,with liver transplantation and neoadjuvant treatment(chemotherapy and radiotherapy),the actuarial survival rate is 65%at 5 years and 59%at 10 years.In conclusion,correct staging,neoadjuvant treatment,living donor and priority on the liver transplant waiting list may lead to improved results.

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.

Palliation:Hilar cholangiocarcinoma

Hilar cholangiocarcinomas are common tumors of the bile duct that are often unresectable at presentation. Palliation, therefore, remains the goal in the majority of these patients. Palliative treatment is particularly indicated in the presence of cholangitis and pruritus but is often also offered for high-grade jaundice and abdominal pain. Endoscopic drainage by placing stents at endoscopic retrograde cholangio-pancreatography(ERCP) is usually the preferred modality of palliation. However, for advanced disease, percutaneous stenting has been shown to be superior to endoscopic stenting. Endosonography-guided biliary drainage is emerging as an alternative technique, particularly when ERCP is not possible or fails. Metal stents are usually preferred over plastic stents, both for ERCP and for percutaneous bili-ary drainage. There is no consensus as to whether it is necessary to place multiple stents within advanced hi-lar blocks or whether unilateral stenting would suffice. However, recent data have suggested that, contrary to previous belief, it is useful to drain more than 50% of the liver volume for favorable long-term results. In the presence of cholangitis, it is beneficial to drain all of the obstructed biliary segments. Surgical bypass plays a limited role in palliation and is offered primarily as asegment Ⅲ bypass if, during a laparotomy for resec-tion, the tumor is found to be unresectable. Photody-namic therapy and, more recently, radiofrequency abla-tion have been used as adjuvant therapies to improve the results of biliary stenting. The exact technique to be used for palliation is guided by the extent of the bili-ary involvement(Bismuth class) and the availability of local expertise.

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.

Perihilar cholangiocarcinoma: Current therapy

Perihilar cholangiocarcinoma, which is a rare primary malignancy, originates from the epithelial cells of the bile duct. Usually invading the periductal tissues and the lymph nodes, perihilar cholangiocarcinoma is commonly diagnosed in the advanced stage of the disease and has a dismal prognosis. Currently, complete hepatectomy is the primary therapy for curing this disease. Perioperative assessment and available surgical procedures can be considered for achieving a negative margin resection, which is associated with long-term survival and better quality of life. For patients with unresectable cholangiocarcinoma, several palliative treatments have been demonstrated to produce a better outcome; and liver transplantation for selected patients with perihilar cholangiocarcinoma is promising and desirable. However, the role of palliative treatments and liver transplantation was controversial and requires more evidence and substantial validity from multiple institutions. In this article, we summarize the data from multiple institutions and discuss the resectability, mortality, morbidity and outcome with different approaches.

Current therapy of hilar cholangiocarcinoma

BACKGROUND: Hilar cholangiocarcinoma (HC) is an adeno-carcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. This tumor is still considered to be difficult to treat or to cure. DATA SOURCES: We reviewed the medical literature on HC. Relevant and updated information on this tumor was analyzed in a concise and easy-to-read manner. The article is not intended to be a systematic review, but an extensive search was conducted on PubMed and MEDLINE using the keywords 'hilar cholangiocarcinoma' and 'Klatskin tumor' until July 2011. RESULTS: The selection and the timing of management options for patients with HC are determined by the degree of certainty of the diagnosis, the general condition of the patients, the underlying liver function and the stage of the disease. Current treatment of HC can be divided into curative and palliative treatment. For the curative treatment, local excision should only be used on small tumors which are confined to the bile duct wall and Bismuth I papillary carcinoma. Partial hepatectomy should be combined with caudate lobe resection and porta-hepatis lymph node dissection. The results of these major resections can be improved with portal vein embolization, and staging laparoscopy and laparoscopic ultrasound. The role of preoperative biliary drainage is controversial. Autotransplantation for HC gave disappointing results while the Mayo Protocol of chemoradiation for selecting patients with unresectable HC for orthotopic liver transplantation has been widely accepted. Palliative treatment included bypass surgery, endoscopic or percutaneous stenting, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy. CONCLUSIONS: Adequate surgery with R0 resection should be the main goal of treatment. For patients with unresectable HC, treatment aims to improve the quality and quantity of their survival.

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA)is a malignant tumor of the biliary system and includes,according to the anatomical classification,intra hepatic CCA(iCCA),hilar CCA(hCCA)and distal CCA(dCCA).Hilar CCA is the most challenging type in terms of diagnosis,treatment and prognosis.Surgery is the only treatment possibly providing long-term survival,but only few patients are considered resectable at the time of diagnosis.In fact,tumor’s extension to segmentary or subsegmentary biliary ducts,along with large lymph node involvement or intrahepatic metastases,precludes the surgical approach.To achieve R0 margins is mandatory for the disease-free survival and overall survival.In case of unresectable locally advanced hCCA,radiochemotherapy(RCT)as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation.Before liver surgery,RCT is believed to enhance the R0 margins rate.For patients meeting the Mayo Clinic criteria,RCT prior to orthotopic liver transplant(OLT)has proved to produce acceptable 5-years survivals.In this review,we analyze the current role of neoadjuvant RCT before resection as well as before OLT.

Pathological aspects of so called "hilar cholangiocarcinoma"

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group.However,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar CC.Grossly,a major distinction can be made between papillary and non-papillary tumors.Histologically,most hilar CCs are well to moderately differentiated conventional type(biliary) carcinomas.Immunohistochemically,CK7,CK20,CEA and MUC1 are normally expressed,being MUC2 positive in less than 50% of cases.Two main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is reviewed.Most(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring cells.IPNB was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

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.

Hilar cholangiocarcinoma

Hilar cholangiocarcinoma(HC) is a rare tumor.It accounts for 2/3 of the tumors of the biliary tract.Untreated,prognosis is very poor.Surgery is the only therapy that offers the possibility of cure but is technically very complex.With recent improvements in the therapeutic strategies applied by multidisciplinary teams,survival rates in the different series currently range from 25% to 45%.A group of experts devoted to HC(pathologists,gastroenterologists,radiologists,surgeons and oncologists) have reviewed and updated every open question in HC in a special issue.

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，

西吡氯铵含漱液治疗口腔念珠菌感染的护理配合

目的探讨西吡氯铵含漱液治疗口腔念珠菌感染的护理配合。方法选取2013年1月～2014年6月间我院收治并确诊的60例口腔念珠菌感染的患者，所有患者均使用西吡氯铵含漱液（浓度0．1％）辅助治疗，总结护理经验。结果6N疗程结束后，60名口腔念珠菌感染患者均得以治愈，治愈率为100％。6周后进行回访，所有患者对治疗期间的护理指导均表示满意。结论口腔念珠菌感染为真菌性疾病，临床治疗周期较长，规范的护理指导可以使患者更好地配合临床治疗及用药，以提高疾病的治愈率，获得理想的疗效。

Intrahepatic cholestasis without jaundice

BACKGROUND:Cholangiocarcinoma(CC),the most common biliary tract malignancy,is frequently seen in advanced unresectable stages and is typically localized extrahepatically.Early diagnosis is unusual because of nonspecific symptoms.Painless jaundice is usually the first sign of tumor. METHOD:We present a patient with a CC(Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS:A 67-year-old woman presented with persisting elevation of liver parameters.Diagnostic tests showed a Klatskin tumor typeⅡ.A curative right hepatic trisegmentectomy was performed after liver volume augmentation by preoperative vein embolization. CONCLUSIONS:A direct drainage of the right posterior bile duct into the common bile duct as an aberrant hepatic duct is a rare variation and is present in less than 5%of the population.In case of persistently perturbed liver function tests,an aberrant bile duct can cover up severe intrahepatic cholestasis and even obscure the diagnosis of a Klatskin tumor.Up to now it has not been described in the literature.

原位肝脏移植治疗Klatskin瘤的价值

目的总结原位肝脏移植治疗Klatskin瘤的适应证及临床疗效。方法选取1992年1月至2003年12月实施的240例原位肝脏移植中的5例Klatskin瘤患者,并与同期具有可比性的采用非移植治疗的35例Klatskin瘤患者进行对比分析。结果肝脏移植组5例患者手术切除率和根治切除率均为100%,除1例因并发症于术后40d死亡外,余均健康存活,现已分别存活48,38,21和5个月,生活质量良好,未见明确肿瘤复发和转移;1、3年累积生存率均为4/5。非移植方法治疗组手术切除率和根治切除率分别为63.0%(17/27)和40.7%(11/27),1,3,5年累积生存率分别为32.2%,8.0%和0,与肝脏移植组相比,在根治切除及生存率方面两组差异有统计学意义(P=0.016)。但非移植方法治疗组行根治切除患者的1,3年累积生存率分别为54.5%(6/11)和18.2%(2/11),与肝脏移植组相比无显著差异(P=0.164)。结论常规无法根治切除的Klatskin瘤是原位肝脏移植的适应证,术后长期疗效满意。

交叉支架治疗肝门部胆管癌引起的梗阻性黄疸

目的探索交叉式支架置入方式,在治疗肝门部胆管癌(HCCA)所致梗阻性黄疸中的可行性及优越性。方法搜集2017年4月至2020年5月9例HCCA引起梗阻性黄疸的患者,行交叉式支架置入,病变均为BismuthⅣ型。手术采用经皮肝穿刺的方式穿刺肝内胆管,若合并严重胆管炎;或肝内胆管迂曲扩张明显,不利于位置关系的判断;或肝门部梗阻严重,导丝不能通过,则先行胆管外引流,择期再行支架置入。若导丝、导管可通过肝门部胆管汇管区,则可行肝门部狭窄段胆管的球囊扩张,然后以"十"型或")("型方式置入内支架。对交叉支架的技术成功率、临床成功率、并发症发生率、支架通畅时间等进行总结分析。结果 9例中8例成功置入交叉支架(7例"十字"交叉,1例")("型交叉),技术成功率88.9%,1例交叉支架无法完成,改行"Y"型支架置入。临床成功率62.5%,平均支架通畅时间221.3天(53~527天),2例术后发生胆管感染,未发生严重胆管出血、腹腔出血、胆汁性腹膜炎等并发症,随访期间2例死亡。结论交叉式支架置入是一种技术成功率较高的解除BismuthⅣ型胆管梗阻的方法,在不增加穿刺通道和支架数量的前提下,理论上可以比现有的支架置入方式多引流约30%的肝脏体积,确切临床疗效尚需大宗病例进一步证实。

肝门部胆管癌临床治疗的研究进展

肝门部胆管癌是指原发于胆囊管开口以上的肝总管及左、右肝管起始部或者汇合部的一类恶性肿瘤。其起病隐匿，早期难以发现，且极易侵犯肝脏以及周围的血管、神经、淋巴结，因而预后较差。近年来，随着研究的深入、影像学技术不断进步和各种治疗方法的涌现与改进，肝门部胆管癌的临床治疗研究取得了较大进展。目前，其治疗手段包括手术切除、肝移植、姑息性胆道引流、放疗、化疗、光动力疗法、生物靶向治疗等，其中手术切除仍是唯一可能治愈肝门部胆管癌的手段。本文就近年来肝门部胆管癌的临床治疗研究进展做一综述，以期为临床上选择最佳治疗方案提供参考依据。

可手术切除的肝门部胆管癌术前胆道引流治疗争议

目的探讨可手术切除的肝门部胆管癌术前胆道引流的利弊、术前胆道引流的时机及各种引流方式的特点。方法通过查阅近20年来国内外相关文献,对可手术切除的肝门部胆管癌术前胆道引流治疗相关争议、术前胆道引流时机及各种引流方式进行综述。结果对于可手术切除的肝门部胆管癌是否需常规行术前胆道引流尚存在很大争议,但对于术前胆道引流时机有较一致的共识,且各种引流方式各有特点。结论肝门部胆管癌主要治疗方式为根治性外科手术切除,但常因胆道恶性梗阻引起胆汁淤积,为围手术期管理带来难度。对于可手术切除的肝门部胆管癌患者是否需常规行术前胆道引流治疗仍需大量前瞻性研究提供更多证据。

内镜超声检查在肝门部胆管癌诊断和术前评价中的作用

目的探讨内镜超声检查术(endoscopic ultrasonography,EUS)在肝门部胆管癌诊断和术前评价中的价值。方法回顾性收集2016年4月—2019年12月在海军军医大学第三附属医院因肝门部胆管狭窄行EUS检查,并经手术后病理确诊为肝门部胆管癌的病例。记录并分析患者的临床信息、EUS影像特征和淋巴结情况。结果最终纳入58例患者,肝门部病变EUS表现为血流不丰富的胆管占位和(或)胆管壁不对称增厚,其中胆管占位45例(77.6%)、胆管壁增厚32例(55.2%),两者并存19例(32.8%)。EUS扫查发现血管侵犯共10例,其中侵犯门静脉3例、肝动脉4例,同时侵犯3例;术后病理发现血管侵犯共14例,诊断符合率为71.4%(10/14)。在53例患者中共扫查到101枚淋巴结,恶性淋巴结表现为低回声、圆形或椭圆形、内部回声均匀。与良性淋巴结相比,恶性淋巴结具有较高的形态学评分(11.41±0.6比9.01±0.15,P<0.001),而两者大小差异无统计学意义[(13.29±0.90)mm比(11.87±0.56)mm,P=0.28]。以淋巴结EUS形态学评分≥12分为恶性诊断标准,EUS判断恶性淋巴结的准确率、敏感度、特异度、阳性预测值、阴性预测值分别为92.1%(93/101)、76.5%(13/17)、95.2%(80/84)、76.5%(13/17)、95.2%(80/84)。结论EUS可显示整个肝外胆管及部分肝内胆管,明确病变范围,有助于肝门部胆管癌的诊断及指导制定手术方案。