Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM: To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma (ICC). METHODS: We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003. Of these, 429 (8.1%) patients were diagnosed with ICC, and their clinicopathological, surgical, and survival characteristics were analyzed. RESULTS: Upper abdominal discomfort or pain (65.0%), no symptoms (12.1%), and hypodynamia (8.2%) were the major causes for medical attention. Laboratory tests showed 198 (46.4%) patients were HBsAg positive, 90 (21.3%) had α-fetoprotein > 20 μg/L, 50 (11.9%) carcinoembryonic antigen > 10 μg/L, and 242 (57.5%) carbohydrate antigen 19-9 (CA19-9) > 37 U/mL. Survival data was available for 329 (76.7%) patients and their mean survival time was 12.4 mo. The overall survival of the patients with R0, R1 resection and punching exploration were 18.3, 6.6 and 5.6 mo, respectively. Additionally, CA19-9 > 37 U/mL was associated with lymph node metastases, but inversely associated with cirrhosis. Multivariate analysis indicated that radical resection, lymph node metastases, macroscopic tumor thrombi and size, and CA19-9 were associated with prognosis.CONCLUSION: Surgical radical resection is still the most effective means to cure ICC. Certain laboratory tests (such as CA19-9) can effectively predict the survival of the patients with ICC.     

机器人与开腹手术治疗肝内胆管细胞癌患者近期疗效研究*

目的 比较机器人与传统开腹手术行肝叶切除术治疗肝内胆管细胞癌(ICC)患者的安全性和短期疗效。方法 2019年1月～2020年12月我院诊治的ICC患者27例,其中9例接受机器人手术,18例接受传统开腹肿瘤根治术,比较两组手术情况。结果 两组均完成肿瘤根治术;机器人组和开腹组患者手术时间【(198±32)分对(215±74)分】、术中出血量【200(100,250) ml对(275(200,300)ml】和术中输血次数(0次对2次)均无统计学差异(P>0.05);机器人组和开腹组患者肿瘤直径【4.0(2.5,5.5) cm 对6.3(3.9,6.5) cm】、R0切除率(100.0%对88.0%)和淋巴结转移率(44.4%对38.9%)比较,差异无统计学意义(P>0.05);机器人组术后卧床时间和住院日分别为2(1,2.5)d和7(4,8)d,显著短于开腹组【分别为3(1.8,3.5)d和11(8,12)d,P<0.05】,机器人组住院费用为11.3(9.1,13.5)万,与开腹组的10.1(8.8,11.5)万比,无统计学差异(P>0.05);两组术后并发症发生率为11.1%和27.8%,无统计学差异(P>0.05)。结论 开展机器人肿瘤根治术治疗ICC患者安全,术后恢复快。     

Liver transplantation for intrahepatic cholangiocarcinoma

The indication of liver transplantation for intrahepatic cholangiocarcinoma (ICC) is highly controversial. Initially, liver transplantation was embraced as a promising treatment for ICC, providing both a wider surgical margin and a potential cure for the underlying liver disease. However, the majority of transplant centers have abandoned liver transplantation for ICC due to poor long‐term survival and high recurrence rates. Interestingly, these decisions were based on studies with highly inconsistent outcomes due to a limited number of patients, various patient selection criteria, and the use of nonstandardized adjunctive therapy protocols. Indeed, recent studies have revealed that ICC patients with small solitary tumors have excellent long‐term survival after liver transplantation. Moreover, as seen in early‐stage hilar cholangiocarcinoma, neoadjuvant and adjuvant therapy hold promise for improved long‐term survival in patients with locally advanced ICC. As we work to expand treatment options for ICC, further evidence of success in this area is needed in order to justify the use of limited organ resources to treat ICC. Continued efforts to improve diagnosis of ICC, hone patient selection criteria, and implement standardized treatment protocols could provide certain patients with ICC access to potentially life‐saving liver transplantation.     

Hepatitis B virus infection and intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC)is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium.The incidence and mortality of ICC is markedly increasing over the past two decades worldwide,though the cause for this rise in incidence is unclear,thus intensifying the search for alternative etiological agents and pathogenetic mechanisms.Hepatolithiasis,primary sclerosing cholangitis,parasitic infection(Opisthorchis viverrini or Clonorchis sinensis),fibropolycystic liver disease,and chemical carcinogen exposure are thought to be the risk factors for ICC.Nevertheless,the majority of ICC patients do not have any of these risk factors,and none of the established risk factors can explain the recent increasing trend of ICC.Therefore,identifying other risk factors may lead to the prevention and early detection of ICC.Chronic hepatitis B virus(HBV)infection is the predominant cause of hepatocellular carcinoma in HBVendemic areas.This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.     

肝内胆管细胞癌外科治疗进展

手术切除是肝内胆管细胞癌首选的治疗方法,也是唯一可能的治愈手段。R0切除是影响肝内胆管细胞癌手术预后的重要因素,在保证R0切除和手术安全性的基础上,切缘距离应>10 mm。淋巴结是否转移是肝内胆管细胞癌手术最重要的预后因素之一,淋巴结清扫能改善患者的预后,术后辅以系统治疗可以延长患者的生存期。对于起始不可切除的肝内胆管细胞癌患者,辅助化疗是一个可能获得根治性手术切除机会的有效措施。     

肝内胆管癌患者术后预后研究

目的 探讨影响肝内胆管癌（ICC）患者术后生存的因素。方法 2011年12月~2015年2月我院诊治的ICC患者94例,对其中35例行姑息性治疗,即肝内扩张胆管置管引流术,对另59例行根治性肿瘤切除术。采用单因素分析和多因素回归分析影响ICC患者术后生存的因素。结果 经随访,本组94例ICC患者生存期为3~35个月,平均为（26.1±4.6）个月;1 a生存率为76.6%,2a生存率为7.4%;单因素分析显示,ICC肿瘤数目、直径、肿瘤分化、血清CEA、CA19-9和是否发生淋巴结转移和远处转移以及手术方法为影响术后患者生存的因素（P<0.05）;经多因素回归分析,发现肿瘤多发、低程度分化、血清CEA大于25 μg/L、血清CA19-9大于182 U/ml、手术切除组织边缘肿瘤细胞阳性、淋巴结转移和姑息性手术是影响ICC患者术后生存的危险因素（P<0.05）。结论 ICC患者预后差,很多患者在诊断时已失去根治性切除肿瘤的机会,即使获得肿瘤切除而根治的患者仍存在很多影响预后的危险因素,临床医生需认真研究这些因素,而给予相应的处理。     

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma （ICC） is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.     

Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma

We present a rare case of intrahepatic cholangiocarcinoma(ICC)with multiple skeletal muscle metastases.The patient was a 55-year-old Asian woman presenting with abdominal pain;abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area.After 3 mo of treatment with palliativeradiotherapy and chemotherapy,magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases.We performed an ultrasound-guided percutaneous fineneedle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma.The patient treated with palliative chemotherapy and achieved 10 mo of survival.Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment,compare to the other cases reported muscle metastases at diagnosis.     

Surgical treatment for intrahepatic cholangiocarcinoma in Europe: a single center experience

Intrahepatic cholangiocarcinoma is the second most common primary liver tumor. The aim of this study was to analyze retrospectively the outcome of surgical treatment and prognostic factors. Clinical, histopathological and treatment data of 221 patients treated from 1995 to 2010 at our institution were investigated. Univariate and multivariate analysis of the patient's data was performed. Patients after R0 and R1 resection presented an overall survival of 67% and 54.5% after 1 year and 40% and 36.4% after 3 years, respectively. The survival of patients without resection of the tumor was dismal with 26% and 3.4% after 1 and 3 years, respectively. Survival after resection was not statistically different in cases with R0 versus R1 resection (P = 0.639, log rank). Univariate Cox regression revealed that higher T stages are a significant hazard for survival (P = 0.048, hazard ratio (HR): 1.211, 95% confidence interval (CI): 1.002–2.465). Patients with tumor recurrence had a significantly inferior long‐term survival when compared to patients without recurrence (P < 0.001, log rank). Presence of lymph node metastasis (N1) was an independent prognostic factor for survival after resection in risk‐adjusted multivariate Cox regression (P < 0.001, HR: 2.577, 95% CI: 1.742–3.813). Adjuvant chemotherapy did not improve patient survival significantly (P = 0.550, log rank). Surgical resection is still the best treatment option for intrahepatic cholangiocarcinoma regarding the patient's long‐term survival. R0 and R1 resection enable both better survival rates when compared to surgical exploration without resection. T status, N status, and tumor recurrence seem to be the most important prognostic factors after resection.     

Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma

BACKGROUND:

Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision.

OBJECTIVE:

To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration.

METHODS:

Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration.

RESULTS:

Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level >37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, repsectively.

CONCLUSIONS:

The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.     

Molecular pathogenesis of intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment‐refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop with no apparent etiological background. The impact of the stromal compartment on tumor progression as well as resistance to therapy is in vogue, and the epithelial‐stromal crosstalk may present a target for novel treatment strategies. As such, the complexity of tumor cellularity and the molecular mechanisms underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next‐generation sequencing has begun to underline the persistent alterations, which may be the trigger of acquired drug resistance, and the cause of metastasis and disease recurrence. A complex issue that remains is to account for the heterogeneous pool of “backseat” aberrations, which in chromosomal proximity to the causative variant are likely to influence, for example, drug response. This review explores the recent advances in defining the molecular pathways implicated in the development of this devastating disease and, which present putative clinical strategies.     

Epirubicin,cisplatin, and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma

Purpose Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma.Patients and method On day 1, epirubicin 50 mg/m² and cisplatin 60 mg/m² were administered i.v., repeated every 21 days. 5-FU (200 mg/m²/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study.Results Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy.Conclusion ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.     

常规超声和超声造影检查诊断肝内胆管细胞癌

目的 探讨肝内胆管细胞癌(ICC)常规超声和超声造影(CEUS)表现.方法 本组纳入52例ICC患者,常规行超声和CEUS检查,组织病理学诊断.结果 灰阶超声表现为均匀低回声者23例(44.2％,不均匀低回声者22例(42.3％),稍高和高回声者7例(13.5％);彩色多普勒血流(CDFI)表现为0级11例(21.2％...     

肝内胆管细胞癌患者超声造影表现特征分析

目的 分析肝内胆管细胞癌（ICC）的超声造影 (CEUS)表现特征,旨在为临床诊断提供依据。方法 2014年8月~2016年8月我院诊治的ICC患者64例,接受常规CT、MRI和彩色多普勒超声检查,并与CEUS检查结果进行对比分析。结果 64例患者存在64个肝内病灶,其中46例（71.9%）病灶边界较为模糊,18例（28.1%）边界较为清晰;56例（87.5%）病灶呈低回声,术后组织病理学检查表现为中或低分化,8例（12.5%）病灶也呈低回声,但术后病理学检查提示癌细胞为高分化;彩色多普勒超声检查显示,64例肿瘤病灶少血供26例（40.6%）,无血供38例（59.4%）;CEUS显示,33例（51.6%）ICC患者病灶表现为环状增强向内充填, 10例（15.6%）表现为整体条片状高增强,21例（32.8%）表现为无强化。在门脉期,11个（17.2%）病灶可见造影剂灌注未消退,53个（82.8%）病灶未见造影剂灌注。延迟期均未见造影剂存留;超声造影显示病灶范围较大、不规则,无包膜样结构,而常规CT检查则形态较为规则,MRI平扫T1WI呈混杂低信号,T2WI呈混杂略高或高信号,DWI呈高信号。结论 ICC的超声造影主要表现为病灶边界较为模糊、环形灌注、病灶呈现低回声、于动脉期出现一过性增强、无包膜样结构,了解这些特征有助于作出临床诊断。     

FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

AIM:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.METHODS:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 i.v.over 90 min)concurrently with folinic acid(400 mg/m2 i.v.over 120 min)followed by fluorouracil(400 mg/m2 i.v.bolus)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 wk.Tumor response was evaluated by computed tomography scan every 4 cycles.RESULTS:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of follow-up.The response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were observed.Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred.An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 patients.CONCLUSION:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.