Management of Intrahepatic Cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Kodali S
PROVIDER: S-EPMC8198953 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intrahepatic cholangiocarcinoma (ICCA) is a rare and aggressive malignant tumor that arises from the biliary tracts in the liver. Upfront surgery with adjuvant capecitabine in patients with resectable disease is often the standard treatment. Unfortunately, only 20% of patients present with resectable disease and many individuals will develop recurrence or metastatic disease after curative-intent resection. Patients with advanced or metastatic ICCA often require multidisciplinary care with a combination of cytotoxic chemotherapy, targeted therapy, and/or locoregional therapies. Gemcitabine plus cisplatin is currently first line therapy for advanced or metastatic ICCA. In recent years, efforts have been focused to develop more effective targeted therapy, most commonly with FGFR and IDH inhibitors for ICCA. Despite these efforts, ICCA still carries a poor prognosis. We herein review the current clinical management of ICCA focusing on surgical technique and systemic therapies.
| S-EPMC10853998 | biostudies-literature
Project description:The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
| S-EPMC7072580 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. ICC makes up about 10% of all cholangiocarcinomas. It arises from the peripheral bile ducts within the liver parenchyma, proximal to the secondary biliary radicals. Histologically, the majority of ICCs are adenocarcinomas. Only a minority of patients (15%) present with resectable disease, with a median survival of less than 3 years. Multidisciplinary management of ICC is complicated by large differences in disease course for individual patients both across and within tumor stages. Risk models and nomograms have been developed to more accurately predict survival of individual patients based on clinical parameters. Predictive risk factors are necessary to improve patient selection for systemic treatments. Molecular differences between tumors, such as in the epidermal growth factor receptor status, are promising, but their clinical applicability should be validated. For patients with locally advanced disease, several treatment strategies are being evaluated. Both hepatic arterial infusion chemotherapy with floxuridine and yttrium-90 embolization aim to downstage locally advanced ICC. Selected patients have resectable disease after downstaging, and other patients might benefit because of postponing widespread dissemination and biliary obstruction.
| S-EPMC5328612 | biostudies-literature
Project description:MicroRNA expression profiles were sucessfully contructed in 63 patients with ICC and 9 normal intrahepatic bile ducts using a custom microarray containing probes for 1094 miRNAs and an outcome prediction of miRNA signature was successfully identified for predicting prognosis in ICC.
2015-03-06 | GSE53870 | GEO
Project description:An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions.
| S-EPMC4527852 | biostudies-literature
Project description:Biliary tract cancer (BTC) is a heterogeneous group of cancers, which is composed of intrahepatic cholangiocarcinoma (ICCA), extrahepatic cholangiocarcinoma (ECCA), gallbladder cancers and ampullary carcinomas. While all anatomic subgroups are treated uniformly, our understanding about the pathogenesis has allowed us to reason that each group represents a clinically and genetically diverse disease. The majority of patients present with locally advanced or metastatic disease, where the standard treatment is combination systemic cytotoxic chemotherapy with gemcitabine and cisplatin. While most receive a clinical benefit from chemotherapy, patients eventually progress where no standardized therapies are available in the refractory setting. With the use of next generation sequencing, we have come to understand that ICCA is a diverse genomic disease with many actionable alterations that may serve as potential therapeutic targets. Further studies investigating the role of novel targeted agents (as a single agent or with combination chemotherapy) will hopefully provide additional treatment options for this highly lethal disease.
| S-EPMC5411274 | biostudies-literature
Project description:No personalized therapy regimens could demonstrate a benefit in survival of intrahepatic cholangiocarcinoma (iCCA). Since genetic heterogeneity might influence single biopsy based targeted therapy or the outcome of clinical trials, aim of the present study was to investigate intratumoral heterogeneity of iCCA by whole exome sequencing. Therefore, samples from tumor center and tumor periphery of large iCCA lesions as well as a control from healthy liver tissue were obtained from four patients and whole exome sequencing was performed. Mutations that occurred only in the tumor center or periphery were defined as private, whereas mutations present in both samples were regarded as common. A mean of 3 non-synonymous private mutations (range 0-14) per sample compared to 33,3 common mutations per sample (range 24-41) was identified. Mean percentage of non-synonymous private mutations per sample was 12% (range 0-58). In all samples of patient 1-3 as well as the central sample of patient 4 ≤ 10% private mutations were found, whereas 58% of private mutations were identified in the peripheral sample of patient 4. In this sample a private mutation in the DNA mismatch repair protein MSH6 could be identified most likely causing the high amount of private mutations. No substantial intratumoral heterogeneity was found in copy number variation analysis. In conclusion, iCCA show a small but distinct intratumoral heterogeneity. Somatic mutations in mismatch repair proteins might contribute significantly to increased spatial tumor burden and thereby may influence clinical management.
| S-EPMC5362457 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with an increasing incidence worldwide and poor prognosis, despite several advances and continuous efforts to develop effective treatments. Complete surgical resection is the mainstay of treatment and offers a potentially curative option, but is only possible in less than a third of patients, owing to advanced disease. Chemotherapy is a well-established treatment in the adjuvant and palliative setting, however, confers limited benefit. Conventional radiotherapy is challenging due to local toxicity. With recent advances in stereotactic ablative radiotherapy (SABR), it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera. This review details the history, technical background and application of SABR to iCCA, with directions for future research suggested.
| S-EPMC9412934 | biostudies-literature
Project description:This review aims to summarize the currently available evidence for the role of external radiotherapy and brachytherapy in the management of cholangiocarcinoma. High locoregional disease recurrence rates after surgical resection alone for both the extrahepatic cholangiocarcinoma (EHCC) and intrahepatic cholangiocarcinoma (IHCC) provide a rationale for using adjuvant radiotherapy with chemotherapy. We performed a literature search related to radiotherapy in cholangiocarcinoma published between 2000 and 2016. The role of radiation is discussed in the adjuvant, neoadjuvant, definitive and the palliative setting. Evidence from Phase II trials have demonstrated efficacy of adjuvant chemoradiation in combination with chemotherapy in EHCC. Locally advanced cholangiocarcinoma may be treated with neoadjuvant chemoradiotherapy. In the case of downsizing, assessment for resection may be considered. Brachytherapy offers dose escalation after external radiotherapy. Selected unresectable cases of cholangiocarcinoma may be considered for stereotactic body radiation therapy with neoadjuvant and/or concurrent chemotherapy. Liver transplantation is a treatment option in selected patients with EHCC and IHCC after neoadjuvant chemoradiation. Stenting in combination with palliative external radiotherapy and/or brachytherapy provides improved stent patency and survival. Newer advanced radiation techniques provide a scope for achieving better disease control with reduced morbidity. Effective multimodality treatment incorporating radiotherapy is the way forward for improving survival in patients with cholangiocarcinoma.
| S-EPMC5603950 | biostudies-literature
Project description:The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarcinoma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.
| S-EPMC9326512 | biostudies-literature