Indications for surgical treatment of intrahepatic cholangiocarcinoma with lymph node metastases

Background/Purpose

The postoperative outcome of patients who have intrahepatic cholangiocarcinoma with lymph node metastases is extremely poor, and the indications for surgery for such patients have yet to be clearly established.

Methods

The demographic and clinical characteristics of 133 patients who underwent lymph node dissection during hepatic resection of intrahepatic cholangiocarcinoma were retrospectively analyzed.

Results

Multivariate analysis identified three independent prognostic factors: intrahepatic metastasis, nodal involvement, and tumor at the margin of resection. Of the patients with tumor-free surgical margins, none of the 24 patients who had both lymph node metastases and intrahepatic metastases survived for 3 years. In contrast, the survival rates for the 23 patients who had lymph node metastases associated with a solitary tumor were 35% at 3 years and 26% at 5 years.

Conclusions

Surgery alone cannot prolong survival when both lymph node metastases and intrahepatic metastases are present, while surgery may provide a chance for long-term survival in some patients who have lymph node metastases associated with a solitary intrahepatic cholangiocarcinoma tumor.

     

Surgery and chemotherapy for intrahepatic cholangiocarcinoma

Cholangiocarcinoma, arising from bile duct epithelium, is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), including hilarcholangiocarcinoma. Recently, there has been a worldwide increase in the incidence and mortality from ICC. Complete surgical resection is the only approach to cure the patients with ICC. However, locoregional extension of these tumors is usually advanced with intrahepatic and lymph-node metastases at the time of diagnosis. Resectability rates are quite low and variable (18%-70%). The five-year survival rate after surgical resection was reported to be 20%-40%. Median survival time after ICC resection was 12-37.4 mo. Only a small number of ICC cases, accompanied with ECC, gall bladder carcinoma, and ampullary carcinoma, have been reported in the studies of chemotherapy due to the rarity of the disease. However, in some reports, significant anti-cancer effects were achieved with a response rate of up to 40% and a median survival of one year. Although recurrence rate after hepatectomy is high for the patients with ICC, the residual liver and the lung are the main sites of recurrence after tentative curative surgical resection. Several patients in our study had a long-term survival with repeated surgery and chemotherapy. Repeated surgery, combined with new effective regimens of chemotherapy, could benefit the survival of ICC patients.     

Predictive risk-score model to select patients with intrahepatic cholangiocarcinoma for adjuvant chemotherapy

BackgroundThe aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC).MethodsPatients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC.ResultsAmong 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04–1.31), tumor burden score (HR1.09, 95%CI 1.04–1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73–2.64), nodal disease (N1, HR3.80, 95%CI 2.02–7.15), tumor grade (HR1.88, 95%CI 1.00–3.55), and morphological subtype (HR2.19, 95%CI 1.08–4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk_model_for_AC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors.ConclusionAn online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC.     

Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not improve survival

Background

Nodal positivity is a predictor of poor survival following resection for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the impact of surgical resection on survival in patients with lymph node (LN) positive ICC.

Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein

AIM：To explore clinicopathologic characteristics of intrahepatic cholangiocarcinoma （ICC） in patients with positive serum a-fetoprotein （AFP）. METHODS：One hundred and thirty one patients who underwent surgical dissection for pathologically confirmed ICC were divided into a positive AFP （〉 20 ng/mL） group （n = 32） and a negative AFP group （n = 99）, whose clinicopathologic features were analyzed and compared. RESULTS：The positive rate of HBsAg and liver cirrhosis of the positive AFP group was higher than that of the negative AFP group, while the positive rate of CA19-9 （〉 37 U/mL） and the lymph node metastasis rate was lower. CONCLUSION：ICC patients with positive AFP share many clinicopathologic similarities with hepatocellular carcinoma.     

Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases

Purpose  

To evaluate the role of radiotherapy for patients with resected intrahepatic cholangiocarcinoma with concurrent macroscopic abdominal lymph node metastases.     

Surgical treatment for intrahepatic cholangiocarcinoma

Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC.     

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。     

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.     

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma

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Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma

BACKGROUND AND AIMS: Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. PATIENTS AND METHODS: We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. RESULTS: Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). CONCLUSIONS: Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.     

腹腔镜肝切除术与开腹肝切除术治疗肝内胆管细胞癌患者短期临床疗效研究

目的 研究腹腔镜肝切除术(LH)与开腹肝切除术(OH)治疗肝内胆管细胞癌(ICC)患者的短期临床疗效。方法 2018年2月～2021年2月我院诊治的122例ICC患者,被随机分为对照组61例和观察组61例,分别接受OH或LH治疗,随访观察半年。采用ELISA法检测血清C反应蛋白(CRP)、皮质醇(Cor)和白细胞介素-6(IL-6)。结果 LH组手术时长、术中失血量、肛门首次排气和术后住院日分别为(232.2±50.4)min、(592.3±164.7)ml、(2.1±0.8)d和(6.5±1.3)d,显著短于或少于0H组【分别为(321.1±69.7)min、(995.5±321.4)ml、(2.7±0.7)d和(8.2±1.7)d,P<0.0 5】;在术后3 d时,LH组血清CRP、Cor和IL-6水平分别为(25.1±4.0)mg/L、(529.6±75.4)mmol/L和(83.5±7.2)pg/ml,均显著低于0H组【分别为(39.8±5.1)mg/L、(654.7±78.1)mmol/L和(97.3±10.2)pg/ml,P<0.05】;在术后7 d时,LH组血...     

The lymph node ratio optimises staging in patients with node positive colon cancer with implications for adjuvant chemotherapy

Purpose

The ratio of positive lymph nodes to total retrieved lymph nodes (lymph node ratio, LNR) has been proposed to be the superior prognostic score in colon cancer. This study aimed to validate LNR in a large, multi-centred population, focusing on patients that have undergone adjuvant chemotherapy.

Methods

Analysis of a prospectively collected database (The West of Scotland Colorectal Cancer Managed Clinical Network) with 1,514 patients with colonic cancer identified that had undergone elective curative surgical resection in the 12 hospitals in the West of Scotland from 2000–2004. Variables recorded were as follows: demographics, adjuvant chemotherapy, number of lymph nodes retrieved, lymph node retrieval ≥12, number of positive lymph nodes and LNR. Follow up continued until June 2009. Univariate and multivariate analyses were performed to determine the influence of LNR on overall survival.

Results

In 673 patients (44.5 %), ≥12 lymph nodes were retrieved. Patients had a poorer long-term prognosis with increasing age, T stage and N stage. Retrieval of <12 lymph nodes and increasing LNR were both found to be significantly associated with poorer long-term survival, but on multivariable analysis, LNR was the only independently significant variable. In patients that had received adjuvant chemotherapy, only patients staged in the second lowest LNR group (0.05–0.19) had a significant improvement in long-term survival.

Conclusion

Lymph node ratio is the optimal method of assessing lymph node status and highlights the heterogeneity of patients with node positive disease, altering patient stratification with implications for adjuvant chemotherapy.     

Hepatopancreatoduodenectomy could be allowed for patients with advanced intrahepatic cholangiocarcinoma

BACKGROUND/AIMS: Patients with advanced intrahepatic cholangiocarcinoma (ICC) have a poor outcome even if they undergo extended radical surgery. Hepatopancreatoduodenectomy (HPD; hepatectomy with pancreatoduodenectomy) for ICCs may be expected to provide a favorable outcome if curative resection is reasonable and patients can tolerate the radical major procedure. METHODOLOGY: Between January 1981 and March 2002, 152 hepatic resections were performed for ICC. Of these, 12 patients underwent HPD for ICC at the same institute of Gastroenterology, Tokyo Women's Medical University. HPD for ICC was indicated in patients who (1) require dissection of the peripancreatic lymph nodes, (2) exhibit direct invasion of intrapancreatic bile duct, (3) show signs of intrapancreatic bile ductal growth. RESULTS: Characteristics of the short-term survivors (died within 12 months), compared with long-term survivors (survived more than 12 months), indicated that they were more likely to be positive intrahepatic metastasis, to be positive lymph node metastasis, to be positive portal venous invasion, and margins of resected surface with residual tumor. The actuarial overall 1-, 3-, 5-, 10-year survival rates were 42%, 33%, 33%, and 23%, respectively. The 5-year survival rate in patients without lymph node metastasis was significantly better (p = 0.045) than that of patients with lymph node metastasis. The patients who underwent potentially curative resection had significantly better 5-year survival rates than those who underwent non-curative resection. Four patients survived for at least 5 years and two of these patients survived for more than 10 years. Nine patients developed recurrence after resection, and of these, 5 patients with recurrence died within 12 months after surgery. CONCLUSIONS: HPD is considered to be an efficacious procedure for advanced ICC and long-term survival may be possible in a selected group of patients.     

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。     

Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma

Background

Lymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC.