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Zhao CH, Liu H, Pan T, Xiang ZW, Mu LW, Luo JY, Zhou CR, Li MA, Liu MM, Yan HZ, Huang MS. Idarubicin-transarterial chemoembolization combined with gemcitabine plus cisplatin for unresectable intrahepatic cholangiocarcinoma. World J Gastrointest Oncol 2025; 17:103776. [DOI: 10.4251/wjgo.v17.i4.103776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 01/12/2025] [Accepted: 02/07/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is the second most common liver malignancy with poor prognosis and limited treatment options.
AIM To identify the most effective drug for transarterial chemoembolization (TACE) in cholangiocarcinoma and evaluate the efficacy and safety of combining it with gemcitabine and cisplatin (GemCis) for unresectable iCCA.
METHODS Cholangiocarcinoma cell lines (RBE, HuCC-T1) were treated with 10 chemotherapeutic drugs, and cytotoxicity was assessed by cell counting kit-8 assays. Tumor-bearing nude mice were treated with idarubicin or GemCis, and tumor growth was monitored. Clinical data from 85 iCCA patients were analyzed to evaluate the efficacy and safety of idarubicin-TACE combined with GemCis.
RESULTS Idarubicin demonstrated the highest cytotoxicity, significantly outperforming GemCis, the standard first-line therapies. In tumor-bearing mouse models, idarubicin and GemCis treatments significantly slowed tumor growth, with idarubicin showing particularly pronounced effects on days 12 and 15 (P < 0.05). In retrospective analysis, the median overall survival (OS) and progression-free survival (PFS) in the combination therapy group were significantly longer than those in the GemCis alone group (median OS, 16.23 months vs 10.07 months, P = 0.042; median PFS, 7.73 months vs 6.30 months, P = 0.023). Additionally, major grade 3/4 adverse events (AEs) in the combination therapy group were abdominal pain (26.3% vs 6.5%, P = 0.049) and elevated transaminases (42.1% vs 12.9%, P = 0.038). Most AEs were mild to moderate and manageable.
CONCLUSION Idarubicin demonstrated higher cytotoxicity than GemCis, significantly inhibiting tumor growth in tumor-bearing mouse models. Preliminary clinical results suggest that local idarubicin-TACE combined with GemCis may offer improved survival outcomes for iCCA patients with a manageable safety profile.
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Affiliation(s)
- Cheng-Hao Zhao
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Huan Liu
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Tao Pan
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Zhan-Wang Xiang
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Lu-Wen Mu
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Jun-Yang Luo
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Chu-Ren Zhou
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-An Li
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-Ming Liu
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Hu-Zheng Yan
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
| | - Ming-Sheng Huang
- Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
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Song L, Qingdong W, Shunhang Y, Long L, Guangsheng Z, Guangji Y, Dong W. Efficacy analysis of drug-eluting beads transcatheter arterial chemoembolization combining systemic chemotherapy and immune checkpoint inhibitors in unresectable intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study based on propensity score matching. World J Surg Oncol 2025; 23:21. [PMID: 39856751 PMCID: PMC11761194 DOI: 10.1186/s12957-025-03679-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 01/19/2025] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE To investigate the efficacy and safety of drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE) combined with systemic chemotherapy and immune checkpoint inhibitors in the treatment of unresectable intrahepatic cholangiocarcinoma. METHODS This study used retrospective cohort analysis to collect the clinical data of 209 patients with unresectable intrahepatic cholangiocarcinoma treated in Linyi Cancer Hospital, Affiliated Zhongshan Hospital of Dalian University, Affiliated Central Hospital of Dalian University of Technology from January 2020 to January 2024. The patients were divided into observation group and control group based on their treatment plans. The observation group was treated with DEB-TACE combined with systemic chemotherapy and immune checkpoint inhibitor, and the control group was treated with simple systemic chemotherapy and immune checkpoint inhibitor. Based on propensity score matching analysis, the clinical treatment efficacy, survival prognosis, and incidence of adverse reactions of two groups of patients were evaluated. RESULTS 82 patients in the observation group received DEB-TACE combined with systemic chemotherapy and immune checkpoint inhibitors, The control group of 127 patients were treated with systemic chemotherapy and immune checkpoint inhibitors. After a propensity score matching analysis to control for the consistency of patient age, sex, tumor size, tumor number, Child grade, ECOG score, and tumor stage. Propensity score matching analysis created 71 pairs of patients in 2 groups. The objective response rate (ORR, 76.06%) and disease control rate (DCR, 97.18%) in the observed group were significantly higher than that in the control group (52.11%, 85.92%), Progression-free survival (PFS, 10 months) and overall survival (OS, 17 months) were higher than the control group (8 months, 11 months). The Cox proportional hazards model analysis revealed that, Child grade and treatment modality were independent predictors of PFS and OS in patients. The adverse effects during treatment were similar in the two groups, with no statistical difference. CONCLUSIONS Compared with systemic therapy alone (systemic chemotherapy + immune checkpoint inhibitor), combined DEB-TACE improves the tumor control rate of patients with unresectable intrahepatic cholangiocarcinoma, extends the survival time and without increasing treatment-related adverse effects, which is a safe and feasible treatment modality.
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Affiliation(s)
- Liu Song
- Dalian Medical University, No.9 Western Section, Lvshun South Street, Lvshun District, Dalian, 116044, Liaoning Province, China
- Department of Interventional Therapy, Linyi Cancer Hospital, No.6 East Lingyuan Street, Linyi, 276000, Shandong Province, China
| | - Wang Qingdong
- Department of Interventional Therapy, Linyi Cancer Hospital, No.6 East Lingyuan Street, Linyi, 276000, Shandong Province, China
| | - Yin Shunhang
- Minimally Invasive Interventional Diagnosis and Treatment Center, Affiliated Zhongshan Hospital of Dalian University, No.6 JieFang Street, Zhongshan District, Dalian, 116001, Liaoning Province, China
| | - Li Long
- Department of Interventional Therapy, Linyi Cancer Hospital, No.6 East Lingyuan Street, Linyi, 276000, Shandong Province, China
| | - Zhao Guangsheng
- Minimally Invasive Interventional Diagnosis and Treatment Center, Affiliated Zhongshan Hospital of Dalian University, No.6 JieFang Street, Zhongshan District, Dalian, 116001, Liaoning Province, China.
| | - Yu Guangji
- Department of Interventional Therapy, Linyi Cancer Hospital, No.6 East Lingyuan Street, Linyi, 276000, Shandong Province, China.
| | - Wang Dong
- Dalian Medical University, No.9 Western Section, Lvshun South Street, Lvshun District, Dalian, 116044, Liaoning Province, China.
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, No. 826 Southwest Road, Shahekou District, Dalian, 116089, Liaoning Province, China.
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Luo S, Xiang Z, Li M, Zhao C, Yan H, Huang M. Clinical Effectiveness of Drug-Eluting Microsphere Transcatheter Arterial Chemoembolization Combined with First-Line Chemotherapy as the Initial Treatment for Patients with Unresectable Intrahepatic Cholangiocarcinoma. J Vasc Interv Radiol 2024; 35:1616-1625. [PMID: 39142516 DOI: 10.1016/j.jvir.2024.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 06/29/2024] [Accepted: 08/03/2024] [Indexed: 08/16/2024] Open
Abstract
PURPOSE To evaluate the safety and effectiveness of the combination of drug-eluting microsphere (DEM) transcatheter arterial chemoembolization (TACE) with those of chemotherapy in treating unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS Seventy patients diagnosed with unresectable ICC between January 2016 and December 2020 were retrospectively included in this study. Of these, 39 patients received DEM-TACE and first-line chemotherapy (TACE+Chemo group) and 31 received chemotherapy alone (Chemo group). Propensity score matching was performed to reduce selection bias between the TACE+Chemo and the Chemo groups. Differences in tumor response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between 2 groups. RESULTS The patients in the TACE+Chemo group had better median OS (18.6 vs 11.9 months; P = .018), median PFS (11.9 vs 6.9 months, P = .033), and objective response rates (56.8% vs 13.3%; P < .001) than those in the Chemo group. TRAEs showed a higher incidence of transient elevation of transaminase and abdominal pain in the TACE+Chemo group than in the Chemo group (P < .001). CONCLUSIONS Compared with chemotherapy alone, DEM-TACE combined with first-line chemotherapy may be a viable and safe treatment option for unresectable ICC.
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Affiliation(s)
- Shuyang Luo
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhanwang Xiang
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mingan Li
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chenghao Zhao
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huzheng Yan
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mingsheng Huang
- Department of Interventional Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Esmail A, Badheeb M, Alnahar BW, Almiqlash B, Sakr Y, Al-Najjar E, Awas A, Alsayed M, Khasawneh B, Alkhulaifawi M, Alsaleh A, Abudayyeh A, Rayyan Y, Abdelrahim M. The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma. Pharmaceuticals (Basel) 2024; 17:910. [PMID: 39065760 PMCID: PMC11279608 DOI: 10.3390/ph17070910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06610, USA
| | | | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA;
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ali Awas
- Faculty of Medicine and Health Sciences, University of Science and Technology, Sanaa P.O. Box 15201-13064, Yemen
| | | | - Bayan Khasawneh
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | | | - Amneh Alsaleh
- Department of Medicine, Desert Regional Medical Center, Palm Springs, CA 92262, USA
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
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Sheng X, Qin JM. Mechanism of postoperative recurrence and metastasis of intrahepatic cholangiocellular carcinoma and clinical prevention and treatment strategy. Shijie Huaren Xiaohua Zazhi 2023; 31:753-765. [DOI: 10.11569/wcjd.v31.i18.753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/12/2023] [Accepted: 09/18/2023] [Indexed: 09/28/2023] Open
Abstract
Intrahepatic cholangiocellular carcinoma is a primary adenocarcinoma originating from intrahepatic bile duct epithelial cells. The tumor has no capsule. At the early stage of the tumor, there are infiltration and metastasis along the lymphatic vessels, blood vessels, perineural space, and loose fibrous connective tissue, which are characterized by lymph node metastasis. Due to the absence of characteristic clinical manifestations and the lack of specific molecular markers for early diagnosis, the surgical resection rate is low and the postoperative tumor recurrence and metastasis rate is high. Low efficacy of chemoradiotherapy, molecular targeted drugs, and immunotherapy results in the poor prognosis. Further research of molecular pathology, gene function, and imaging technology can help elucidate the occurrence, recurrence, and metastasis mechanism of intrahepatic cholangiocellular carcinoma to improve its early diagnosis rate and precise clinical staging. Individualized precision treatment and prevention for the risk factors to reduce the recurrence and metastasis rate postoperatively are key to improving the patient prognosis.
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Affiliation(s)
- Xia Sheng
- Department of Pathology, Affiliated Minhang Hospital, Fudan University, Shanghai 201100, China
| | - Jian-Min Qin
- Department of General Surgery, The Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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Owen M, Makary MS, Beal EW. Locoregional Therapy for Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2023; 15:2384. [PMID: 37190311 PMCID: PMC10137284 DOI: 10.3390/cancers15082384] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/08/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable liver-only or liver-dominant ICC. This review explores the role of these therapies in the treatment of ICC, including radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), external beam radiotherapy (EBRT), stereotactic body radiotherapy (SBRT), hepatic arterial infusion (HAI) of chemotherapy, irreversible electroporation (IE), and brachytherapy. A search of the current literature was performed to examine types of LRT currently used in the treatment of ICC. We examined patient selection, technique, and outcomes of each type. Overall, LRTs are well-tolerated in the treatment of ICC and are effective in improving overall survival (OS) in this patient population. Further studies are needed to reduce bias from heterogenous patient populations and small sample sizes, as well as to determine whether certain LRTs are superior to others and to examine optimal treatment selection.
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Affiliation(s)
- Mackenzie Owen
- The Ohio State University College of Medicine, Columbus, OH 43210, USA
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Eliza W. Beal
- Departments of Surgery and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
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Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023; 73:198-222. [PMID: 36260350 DOI: 10.3322/caac.21759] [Citation(s) in RCA: 181] [Impact Index Per Article: 90.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/25/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma. Clin Transl Oncol 2023; 25:731-738. [PMID: 36401766 DOI: 10.1007/s12094-022-02979-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 10/07/2022] [Indexed: 11/21/2022]
Abstract
PURPOSE As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. MATERIALS AND METHODS We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. RESULTS The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p < 0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p < 0.05). CONCLUSION The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.
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Wang J, Xue Y, Liu R, Wen Z, Ma Z, Yang X, Yu L, Yang B, Xie H. DEB-TACE with irinotecan versus C-TACE for unresectable intrahepatic cholangiocarcinoma: a prospective clinical study. Front Bioeng Biotechnol 2023; 10:1112500. [PMID: 36714623 PMCID: PMC9878160 DOI: 10.3389/fbioe.2022.1112500] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 12/30/2022] [Indexed: 01/15/2023] Open
Abstract
Objectives: DEB-TACE with irinotecan and C-TACE were compared with regards to safety and efficacy for the therapy of intrahepatic cholangiocarcinoma (ICC). Methods: Institutional Review Board approved our trial and we registered it in the Chinese Clinical Trial Registry (ChiCTR1900022856). Forty patients with biopsy-confirmed ICC were randomised to either receive DEB-TACE or C-TACE treatment with 20 patients in each treatment arm. The primary endpoints objective response rate (ORR) and progression free survival (PFS) using the mRECIST to evaluate the tumours. The secondary endpoints were overall survival (OS) and safety. The chi-square was used to analyse the data. The Kaplan-Meier method and Cox analysis were used to evaluate the survival data. Results: ORR (70% in DEB-TACE group vs. 20% in C-TACE, p = .001) at 1 month after therapy, ORR (50% vs. 15%, p = .018) at 3 months and DCR (70% vs. 30%, p = .011) at 6 months, while no difference was found in other groups. (all p > .05) The median PFS with DEB-TACE was longer than that with C-TACE (8.0 months vs. 3.0 months) (p = .042). Although the median OS was longer with DEB-TACE than with C-TACE (11.5 months vs. 9.0 months), the difference was not statistically significant (p = .280). The Cox regression analysis demonstrated that TACE sessions (p = .017) and low CA125 levels (p = .001) were independent favourable prognostic factors. The most frequent adverse event was elevated transaminase levels (20/20 in DEB-TACE group vs. 15/20 in C-TACE group) (p = .047). Conclusion: Our prospective study suggested better ORR and PFS with DEB-TACE with irinotecan as compared to C-TACE with irinotecan in the treatment of unresectable ICC.
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Affiliation(s)
- Junxiao Wang
- Aerospace Medical Center, Aerospace Center Hospital, Beijing, China,Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yaoqin Xue
- Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China,Department of Interventional Therapy, Shanxi Province Cancer Hospital, Taiyuan, China
| | - Rui Liu
- Department of Interventional Vascular, Aerospace Center Hospital, Beijing, China
| | - Zhenyu Wen
- Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhenhu Ma
- Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiang Yang
- Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lingxiang Yu
- Senior Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China,*Correspondence: Hui Xie, ; Bin Yang, ; Lingxiang Yu,
| | - Bin Yang
- Senior Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China,*Correspondence: Hui Xie, ; Bin Yang, ; Lingxiang Yu,
| | - Hui Xie
- Senior Department of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China,*Correspondence: Hui Xie, ; Bin Yang, ; Lingxiang Yu,
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Smith EN, Coleman A, J. Galgano S, Burgan CM, Porter KK. Cholangiocarcinoma. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:133-159. [DOI: 10.1016/b978-0-323-69538-1.00011-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Locoregional Approaches in Cholangiocarcinoma Treatment. Cancers (Basel) 2022; 14:cancers14235853. [PMID: 36497334 PMCID: PMC9740081 DOI: 10.3390/cancers14235853] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/20/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a rare hepatic malignant tumor with poor prognosis due to late detection and anatomic factors limiting the applicability of surgical resection. Without surgical resection, palliation is the most common approach. In non-surgical cases contained within the liver, locoregional therapies provide the best chance for increased survival and disease control. The most common methods, transarterial chemoembolization and transarterial radioembolization, target tumors by embolizing their blood supply and limiting the tumor's ability to metabolize. Other treatments induce direct damage via thermal ablation to tumor tissue to mediate their anti-tumor efficacy. Recent studies have begun to explore roles for these therapies outside their previous role of palliation. This review will outline the mechanisms of each of these treatments, along with their effects on overall survival, while comparing these to non-locoregional therapies.
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Zhang N, Yu BR, Wang YX, Zhao YM, Zhou JM, Wang M, Wang LR, Lin ZH, Zhang T, Wang L. Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma. J Dig Dis 2022; 23:535-545. [PMID: 36148493 DOI: 10.1111/1751-2980.13127] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/12/2022] [Accepted: 09/20/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). METHODS Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group) were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. RESULTS A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P = 0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P = 0.004) and disease control rate (DCR; 82.1% vs 36.8%, P = 0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0 months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. CONCLUSIONS For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.
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Affiliation(s)
- Ning Zhang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Bing Ran Yu
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Xiu Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Ming Zhao
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jia Min Zhou
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Miao Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Long Rong Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhen Hai Lin
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ti Zhang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lu Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
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Xu Z, Xu M, Li M, Cui Z, Bai H, Shang H, Zhao J, Wu L, Zhang F. Effects of I125 seed stent implantation combined with arterial infusion chemoembolization on tumor markers, p53 expression, and prognosis in patients with cholangiocarcinoma. Bioengineered 2022; 13:2943-2950. [PMID: 35038960 PMCID: PMC8974219 DOI: 10.1080/21655979.2021.2022263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Cholangiocarcinoma is a common malignant tumor. Advanced treatment is difficult and the prognosis is poor. It is of great significance to find an effective method to treat cholangiocarcinoma and improve the prognosis of patients. Therefore, 78 patients with cholangiocarcinoma treated in our hospital were divided into group A and group B according to different treatment methods. The clinical effect, bilirubin, tumor size, bile duct patency time, tumor marker level To evaluate the therapeutic effect of I125 seed stent implantation combined with arterial infusion chemoembolization in patients with cholangiocarcinoma. The results showed that I125 seed stent implantation combined with TACE in the treatment of patients with cholangiocarcinoma can play an obvious clinical effect, effectively reduce the level of tumor markers and p53, reduce tumor lesions, improve the survival rate of patients, and play an important role in tumor treatment.
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Affiliation(s)
- Zhe Xu
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Minglin Xu
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Meng Li
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Zhe Cui
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Haisheng Bai
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Heqing Shang
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Jianyu Zhao
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Lei Wu
- Department of Interventional Therapy, Hulunbuir People's Hospital, Inner Mongolia China
| | - Fan Zhang
- Department of Reproductive Center, Hulunbuir People's Hospital, Inner Mongolia China
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14
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Mukund A, V Srinivasan S, Rana S, Vijayaraghavan R, Patidar Y, Arora V, Jindal A, Choudhury A, Shasthry SM, Sarin SK. Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study. Clin Radiol 2021; 77:121-129. [PMID: 34789395 DOI: 10.1016/j.crad.2021.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/14/2021] [Indexed: 11/16/2022]
Abstract
AIM To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.
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Affiliation(s)
- A Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - S V Srinivasan
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S Rana
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - R Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Y Patidar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - V Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - A Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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15
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Ben Khaled N, Jacob S, Rössler D, Bösch F, De Toni EN, Werner J, Ricke J, Mayerle J, Seidensticker M, Schulz C, Fabritius MP. Current State of Multidisciplinary Treatment in Cholangiocarcinoma. Dig Dis 2021; 40:581-595. [PMID: 34695826 DOI: 10.1159/000520346] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 10/19/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a highly aggressive malignancy, and its incidence seems to be increasing over the last years. Given the high rate of irresectability at the time of initial diagnosis, new treatment approaches are important to achieve better patient outcomes. Our review provides an overview of current multimodal therapy options across different specialties of gastroenterology/oncology, surgery, and interventional radiology. SUMMARY CCA is subdivided into clinically and molecularly distinct phenotypes. Surgical treatment currently is the only potentially curative therapy, but unfortunately, the majority of all patients are not eligible for resection at the time of initial diagnosis due to anatomic location, inadequate hepatic reserve, metastatic disease, or limiting comorbidities. However, multimodal treatment options are available to prolong survival, relieve symptoms, and maintain life quality. KEY MESSAGES The treatment of CCA is complex and requires close interdisciplinary collaboration and individualized treatment planning to ensure optimal patient care at specialized centers. Molecular profiling of patients and inclusion into clinical trials is highly recommended.
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Affiliation(s)
- Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Sven Jacob
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Daniel Rössler
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Florian Bösch
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Enrico N De Toni
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Jens Werner
- Department of General-, Visceral- and Transplantation-Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Julia Mayerle
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
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Oguz S, Kucukaslan H, Topaloglu S, Ones T, Baltacioglu F, Cobanoglu U, Calik A. Is it Possible to Increase Survival of Patients with Intrahepatic Cholangiocarcinoma? A Case Report. J Gastrointest Cancer 2021; 52:342-346. [PMID: 32617830 DOI: 10.1007/s12029-020-00446-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Sukru Oguz
- Faculty of Medicine, Department of Radiology, Karadeniz Technical University, Trabzon, Turkey
| | - Hakan Kucukaslan
- Faculty of Medicine, Department of Surgery, Karadeniz Technical University, Trabzon, Turkey
| | - Serdar Topaloglu
- Faculty of Medicine, Department of Surgery, Karadeniz Technical University, Trabzon, Turkey.
| | - Tunc Ones
- Faculty of Medicine, Department of Nuclear Medicine, Marmara University, İstanbul, Turkey
| | - Feyyaz Baltacioglu
- Faculty of Medicine, Department of Radiology, Marmara University, İstanbul, Turkey
| | - Umit Cobanoglu
- Faculty of Medicine, Department of Pathology, Karadeniz Technical University, Trabzon, Turkey
| | - Adnan Calik
- Faculty of Medicine, Department of Surgery, Karadeniz Technical University, Trabzon, Turkey
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17
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Li H, Chen L, Zhu GY, Yao X, Dong R, Guo JH. Interventional Treatment for Cholangiocarcinoma. Front Oncol 2021; 11:671327. [PMID: 34268114 PMCID: PMC8276166 DOI: 10.3389/fonc.2021.671327] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/09/2021] [Indexed: 12/11/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the second most common type of primary liver malignancy. The latest classification includes intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with the latter one further categorized into perihilar and distal cholangiocarcinoma. Although surgical resection is the preferred treatment for CCA, less than half of the patients are actually eligible for radical surgical resection. Interventional treatment, such as intra-arterial therapies, ablation, and brachytherapy (iodine-125 seed implantation), has become an acceptable palliative treatment for patients with unresectable CCA. For these patients, interventional treatment is helpful for locoregional control, symptom relief, and improving quality of life. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research in this article.
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Affiliation(s)
- Hang Li
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Li Chen
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Guang-Yu Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Xijuan Yao
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Rui Dong
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jin-He Guo
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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18
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Wang Y, Yu H, Xie X, Deng T, Ye L, Wu L, Ding X, Yang Z, Zhu Q, Li J, Zheng Y, Yu Z, Chen G. Plasmalemma vesicle-associated protein promotes angiogenesis in cholangiocarcinoma via the DKK1/CKAP4/PI3K signaling pathway. Oncogene 2021; 40:4324-4337. [PMID: 34079085 DOI: 10.1038/s41388-021-01844-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 04/26/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is aggressive and has poor clinical outcomes because of typically delayed diagnosis and a lack of effective non-surgical therapeutic options. Recent studies have shown that plasmalemma vesicle-associated protein (PLVAP) is related to angiogenesis in various tumors, and in vivo PLVAP targeting therapy has been proven effective against hepatocellular carcinoma and pancreatic cancer. The goal of this study was to determine the potential therapeutic utility of targeting PLVAP and thus angiogenesis in CCA and explore the underlying molecular mechanisms. We found that the PLVAP expression levels were significantly higher in CCA tissues when compared with matched adjacent non-tumor tissues obtained from a total of 90 CCA patients; higher expression levels of PLVAP were associated with shorter overall survival of patients. In addition, overexpression of PLVAP was associated with higher micro-vessel density in CCA tissues. In a PLVAP overexpressing CCA patient-derived xenograft model, a novel humanized anti-PLVAP antibody in combination with Gemcitabine plus Cisplatin was significantly inhibited tumor growth. Molecular analysis of CCA cells co-cultured with human umbilical vascular endothelial cells or human hepatic sinusoidal endothelial cells showed that Dickkopf-related protein 1 (DKK1) secreted by CCA cells activated the PI3K/Akt pathway after binding to its receptor, cytoskeleton-associated protein 4 (CKAP4), resulting in the upregulation of PLVAP. Thus, CCA cells increased the angiogenic potency of endothelial cells in a paracrine fashion. Consistently, patients bearing CKAP4 and PLVAP overexpressing tumors had a poor prognosis. In conclusion, the DKK1/CKAP4/PI3K/PLVAP pathway increases angiogenesis in CCA and is therefore a potential anti-angiogenic target.
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Affiliation(s)
- Yi Wang
- Division of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
| | - Haitao Yu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaozai Xie
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Tuo Deng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Longyun Ye
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lijun Wu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiwei Ding
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Zhen Yang
- Department of Infectious Diseases, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China
| | - Qiandong Zhu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Junjian Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yihu Zheng
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhengping Yu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Gang Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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19
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Abstract
Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.
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Affiliation(s)
- Pouya Entezari
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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20
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Liu HT, Cheng SB, Lai CY, Chen YJ, Su TC, Wu CC. Locoregional therapies in patients with recurrent intrahepatic cholangiocarcinoma after curative resection. Therap Adv Gastroenterol 2020; 13:1756284820976974. [PMID: 33354228 PMCID: PMC7734491 DOI: 10.1177/1756284820976974] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 10/29/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Hepatectomy is one potential treatment for intrahepatic cholangiocarcinoma (IHCC). Recurrent rate is high after curative resection and most recurrences occur within residual liver parenchyma. The aim of this study was to elucidate the impact of different treatment modalities on recurrent diseases in patients with IHCC after primary liver resection. METHODS Between February 1999 and December 2015, we retrospectively identified patients who received curative resection for IHCC. Patients who experienced recurrences were included. Locoregional therapies included re-hepatectomy, radiofrequent ablation, and transhepatic arterial chemoembolization. These patients were categorized into three groups: intrahepatic recurrence without locoregional therapies (group A), intrahepatic recurrence with locoregional therapies (group B) and extrahepatic metastases (group C). RESULTS Forty-three patients were included and there were 12, 15, and 16 patients in groups A, B, and C, respectively. The median disease-free survival times were 8.3, 9.1, and 8.7 months in groups A, B, and C (p = 0.099). The median after-recurrence overall survival times (period between recurrence and death/censor) were 6.4, 34.0, and 8.3 months in groups A, B, and C (p = 0.001). Locoregional therapies showed favorable benefit in multivariant analysis (hazard ratio: 0.274, confidence interval: 0.083-0.908, p = 0.010). CONCLUSION Locoregional therapies offered favorable benefits for patients with recurrent intrahepatic cholangiocarcinoma.
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Affiliation(s)
| | - Shao-Bin Cheng
- Department of Surgery, Taichung Veterans General Hospital,School of Medicine, Chung Shan Medical University, Taichung
| | - Chia-Yu Lai
- Department of Surgery, Taichung Veterans General Hospital
| | - Yi-Ju Chen
- Department of Surgery, Taichung Veterans General Hospital
| | - Te-Cheng Su
- Department of Radiology, Taichung Veterans General Hospital
| | - Cheng-Chung Wu
- Department of Surgery, Taichung Veterans General Hospital School of Medicine, Chung Shan Medical University, Taichung
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21
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Akateh C, Ejaz AM, Pawlik TM, Cloyd JM. Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma. World J Hepatol 2020; 12:693-708. [PMID: 33200010 PMCID: PMC7643214 DOI: 10.4254/wjh.v12.i10.693] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/21/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
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.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Aslam M Ejaz
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Timothy Michael Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
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22
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Mondaca S, Yarmohammadi H, Kemeny NE. Regional Chemotherapy for Biliary Tract Tumors and Hepatocellular Carcinoma. Surg Oncol Clin N Am 2019; 28:717-729. [PMID: 31472915 DOI: 10.1016/j.soc.2019.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Locally advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma are associated with a grim prognosis. The development of highly effective systemic therapies for these tumors has been challenging; however, numerous locoregional treatment alternatives have emerged, including transarterial hepatic embolization (TAE), transarterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), hepatic arterial infusion chemotherapy (HAI), radioembolization, and stereotactic body radiation therapy. Although there is potential for long-term disease control for these therapies, the evidence to guide adequate patient selection and choose among different treatment alternatives is still limited. This review focuses on the rationale and data supporting TAE, TACE, DEB-TACE, and HAI in hepatobiliary cancers.
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Affiliation(s)
- Sebastian Mondaca
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Hooman Yarmohammadi
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - Nancy E Kemeny
- Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
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23
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Zheng WH, Yu T, Luo YH, Wang Y, Liu YF, Hua XD, Lin J, Ma ZH, Ai FL, Wang TL. Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma. World J Gastrointest Oncol 2019; 11:489-498. [PMID: 31236199 PMCID: PMC6580316 DOI: 10.4251/wjgo.v11.i6.489] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 05/15/2019] [Accepted: 05/29/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients.
AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.
METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed.
RESULTS The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV.
CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.
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Affiliation(s)
- Wen-Heng Zheng
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Tao Yu
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Ya-Hong Luo
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Ying Wang
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Ye-Fu Liu
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xiang-Dong Hua
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Jie Lin
- Department of General Surgery (VIP ward), Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Zuo-Hong Ma
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Fu-Lu Ai
- Department of General Surgery (VIP ward), Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Tian-Lu Wang
- Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
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Pandey A, Pandey P, Ghasabeh MA, Zarghampour M, Khoshpouri P, Ameli S, Luo Y, Kamel IR. Baseline Volumetric Multiparametric MRI: Can It Be Used to Predict Survival in Patients with Unresectable Intrahepatic Cholangiocarcinoma Undergoing Transcatheter Arterial Chemoembolization? Radiology 2018; 289:843-853. [DOI: 10.1148/radiol.2018180450] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Ankur Pandey
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Pallavi Pandey
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Mounes Aliyari Ghasabeh
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Manijeh Zarghampour
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Pegah Khoshpouri
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Sanaz Ameli
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Yan Luo
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Ihab R. Kamel
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
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25
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Reimer P, Virarkar MK, Binnenhei M, Justinger M, Schön MR, Tatsch K. Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients. Cardiovasc Intervent Radiol 2018; 41:744-752. [DOI: 10.1007/s00270-017-1871-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 12/29/2017] [Indexed: 12/18/2022]
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26
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Razumilava N, Lazaridis KN, Gores GJ. Cholangiocarcinoma. ZAKIM AND BOYER'S HEPATOLOGY 2018:693-707.e4. [DOI: 10.1016/b978-0-323-37591-7.00047-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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27
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Ettrich TJ, Seufferlein T. Liver Metastases of Neuroendocrine Tumors and CCC. LOCOREGIONAL TUMOR THERAPY 2018:107-127. [DOI: 10.1007/978-3-319-69947-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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28
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Abstract
Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma.
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29
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Shen ZT, Zhou H, Li AM, Li B, Shen JS, Zhu XX. Clinical outcomes and prognostic factors of stereotactic body radiation therapy for intrahepatic cholangiocarcinoma. Oncotarget 2017; 8:93541-93550. [PMID: 29212171 PMCID: PMC5706817 DOI: 10.18632/oncotarget.19972] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 07/18/2017] [Indexed: 02/07/2023] Open
Abstract
Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with intrahepatic cholangiocarcinoma (ICC) when surgical treatment cannot be applied. The CyberKnife® is a SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the clinical outcomes and prognostic factors for ICC patients receiving this treatment. Twenty-eight patients with ICC were enrolled in the present study. The median prescription dose was 45 Gy (range, 36-54 Gy), fractionated 3 to 5 times with a 70% to 92% isodose line. Local control, overall survival, progression-free survival and toxicity were studied. The median follow-up time was 16 months (3-42 months). Based on modified Response Evaluation and Criteria in Solid Tumors (mRECIST), response rate and disease control rate of SBRT in ICC were 46.4% (13/28) and 89.3% (25/28), respectively. Median overall survival was 15 months (95% CI, 7.22-22.78). 1- and 2-years survival rates were 57.1% and 32.1%, and 1- and 2- years Progression-free Survival rates were 50.0 % and 21.4 %. Multivariate analysis revealed that number of lesions (solitary vs. multiple nodules), CA19-9 levels (≤37 U/mL vs. 37-600/>600) and TNM stage (AJCC stage) were independent prognostic factors for ICC patients treated with SBRT. Toxicity was mostly transient and tolerable. No greater than grade 3 toxicity was observed. These results suggested that CyberKnife SBRT might be a good alternative treatment for unresectable ICC.
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Affiliation(s)
- Ze-Tian Shen
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Han Zhou
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Ao-Mei Li
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Bing Li
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jun-Shu Shen
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xi-Xu Zhu
- Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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30
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Akinwande O, Shah V, Mills A, Noda C, Weiner E, Foltz G, Saad N. Chemoembolization versus radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma in a single institution image-based efficacy and comparative toxicity. Hepat Oncol 2017; 4:75-81. [PMID: 30191056 DOI: 10.2217/hep-2017-0005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 08/22/2017] [Indexed: 01/04/2023] Open
Abstract
Aim Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC). Materials & methods Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's t and fisher-exact tests. Multivariable-logistic regression was also performed. Results Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden. Conclusion Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.
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Affiliation(s)
- Olaguoke Akinwande
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Veer Shah
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Abigail Mills
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Christopher Noda
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Eric Weiner
- Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Gretchen Foltz
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Nael Saad
- Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.,Division of Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
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31
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Gaba RC, Lokken RP, Hickey RM, Lipnik AJ, Lewandowski RJ, Salem R, Brown DB, Walker TG, Silberzweig JE, Baerlocher MO, Echenique AM, Midia M, Mitchell JW, Padia SA, Ganguli S, Ward TJ, Weinstein JL, Nikolic B, Dariushnia SR. Quality Improvement Guidelines for Transarterial Chemoembolization and Embolization of Hepatic Malignancy. J Vasc Interv Radiol 2017; 28:1210-1223.e3. [PMID: 28669744 DOI: 10.1016/j.jvir.2017.04.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 04/29/2017] [Indexed: 02/07/2023] Open
Affiliation(s)
- Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612.
| | - R Peter Lokken
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Ryan M Hickey
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Andrew J Lipnik
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Robert J Lewandowski
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Riad Salem
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Daniel B Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - T Gregory Walker
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Ana Maria Echenique
- Department of Interventional Radiology, University of Miami School of Medicine, Coral Gables, Florida
| | - Mehran Midia
- Interventional Radiology, McMaster University, Hamilton, Ontario, Canada
| | - Jason W Mitchell
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Siddharth A Padia
- Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Suvranu Ganguli
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Thomas J Ward
- Vascular and Interventional Radiology, Florida Hospital, Orlando, Florida
| | - Jeffrey L Weinstein
- Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Boris Nikolic
- Department of Radiology, Stratton Medical Center, Albany, New York
| | - Sean R Dariushnia
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
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32
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Rahnemai-Azar AA, Weisbrod AB, Dillhoff M, Schmidt C, Pawlik TM. Intrahepatic cholangiocarcinoma: current management and emerging therapies. Expert Rev Gastroenterol Hepatol 2017; 11:439-449. [PMID: 28317403 DOI: 10.1080/17474124.2017.1309290] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify 'target-able' molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients. Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies. Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.
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Affiliation(s)
- Amir A Rahnemai-Azar
- a Department of Surgery , University of Washington Medical Center , Seattle , WA , USA
| | - Allison B Weisbrod
- b Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Mary Dillhoff
- b Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Carl Schmidt
- b Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Timothy M Pawlik
- b Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
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33
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Koay EJ, Odisio BC, Javle M, Vauthey JN, Crane CH. Management of unresectable intrahepatic cholangiocarcinoma: how do we decide among the various liver-directed treatments? Hepatobiliary Surg Nutr 2017; 6:105-116. [PMID: 28503558 DOI: 10.21037/hbsn.2017.01.16] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Intrahepatic cholangiocarcinoma often causes death due to obstruction of the biliary system or interruption of the vascular supply of the liver. This fact emphasizes the critical need for local tumor control in this disease. Successful local tumor control has traditionally been achievable through surgical resection for the small proportion of patients with operable tumors. Technological advances in radiation oncology and in interventional radiology have enabled the delivery of ablative radiation doses or other cytotoxic therapies for tumors in the liver. In some cases, this has translated into substantial prolongation of life for patients with this disease, but the indications for these different treatment options are still the subject of ongoing debate. Here, we review the technological advances and clinical studies that are changing the way intrahepatic cholangiocarcinoma is managed, and discuss ways to achieve individualized treatment of patients.
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Affiliation(s)
- Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Milind Javle
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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34
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Rahnemai-Azar AA, Pandey P, Kamel I, Pawlik TM. Monitoring outcomes in intrahepatic cholangiocarcinoma patients following hepatic resection. Hepat Oncol 2017; 3:223-239. [PMID: 30191045 DOI: 10.2217/hep-2016-0009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/04/2016] [Indexed: 02/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is one of the fatal gastrointestinal cancers with increasing incidence and mortality. Although surgery offers the only potential for cure in iCCA patients, the prognosis is not optimal with low overall survival rate and high disease recurrence. Hence, adjuvant therapy is generally recommended in the management of high-risk patients. Identifying factors associated with disease recurrence and survival of the iCCA patients after resection will improve understanding of disease prognosis and help in selecting patients who will benefit from surgical resection or stratifying them for clinical trials. Despite development of new methods for early detection of tumor recurrence, effective prognostic models and nomograms, and recent advances in management, significant challenges remain in improving the prognosis of iCCA patients.
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Affiliation(s)
- Amir A Rahnemai-Azar
- Department of Surgery, University of Washington Medical Center, University of Washington School of Medicine, Seattle, WA, USA.,Department of Surgery, University of Washington Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Pallavi Pandey
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab Kamel
- Department of Radiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Radiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, OH, USA.,Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, OH, USA
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35
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The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma. Med Oncol 2017. [DOI: 10.1007/s12032-016-0866-1
expr 866809535 + 987807487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
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36
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The role of interventional radiology in the treatment of intrahepatic cholangiocarcinoma. Med Oncol 2016; 34:11. [PMID: 28008570 DOI: 10.1007/s12032-016-0866-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 12/07/2016] [Indexed: 12/21/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. Complete surgical resection remains the only potentially curative option for patients with ICC. However, until now, early diagnosis with potential surgical intervention has been the exception rather than the rule with only 30% of patients qualifying for attempted surgical cure. Many patients are unresectable because of disease stage, anatomic conditions, medical comorbidities, and small future remnant liver. Interventional radiology procedures are available for these types of patients with intra-arterial therapies and/or ablative treatments both for curative and for palliative treatment. The goals of interventional therapy are to control local tumor growth, to relieve symptoms, and to improve and preserve quality of life. The choice of treatment depends largely on tumor extent and patient performance. No randomized studies exist to compare treatments. The present review describes the current evidence of the interventional treatments in the management of the ICC. Moreover, interventional procedures available to increase the future liver reserve before surgery were analyzed.
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37
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Abstract
BACKGROUND Cholangiocarcinoma (CC) is the second most primary liver malignancy with increasing incidence in Western countries. Currently, surgical R0 resection is regarded as the only potentially curative treatment. The results of systemic chemotherapy and best supportive care (BSC) in patients with metastatic disease are often disappointing in regard to toxicity, oncologic efficacy, and overall survival. In current practice, the use of different locoregional therapies is increasingly more accepted. METHODS A review of the literature on locoregional therapies for intrahepatic cholangiocarcinoma (ICC) was undertaken. RESULTS There are no prospective randomized controlled trials. For localized ICC, either primary or recurrent, radiofrequency ablation (RFA) is by far the most commonly used thermal ablation modality. Thereby, a systematic review and meta-analysis reports major complication in 3.8% as well as 1-, 3-, and 5-year overall survival rates of 82, 47, and 24%, respectively. In selected patients (e.g. with a tumor diameter of ≤3 cm), oncologic efficacy and survival after RFA are comparable with surgical resection. For diffuse ICC, different transarterial therapies, either chemotherapy-based (hepatic artery infusion (HAI), transarterial chemoembolization (TACE)) or radiotherapy-based (transarterial radioembolization (TARE)), show extremely promising results. With regard to controlled trials (transarterial therapy versus systemic chemotherapy, BSC or no treatment), tumor control is virtually always better for transarterial therapies and very often accompanied by a dramatic survival benefit and improvement of quality of life. Of note, the latter is the case not only for patients without extrahepatic metastatic disease but also for those with liver-dominant extrahepatic metastatic disease. There are other locoregional therapies such as microwave ablation, irreversible electroporation, and chemosaturation; however, the current data support their use only in controlled trials or as last-line therapy. CONCLUSION Dedicated locoregional therapies are commonly used for primary and recurrent ICC as well as liver-only and liver-dominant extrahepatic metastatic disease. Currently, the best evidence and most promising results are available for RFA, HAI, TACE, and TARE. In cohort studies, the overall survival rates are similar to those obtained with surgery or systemic therapies. Prospective randomized controlled trials are warranted to compare safety and efficacy between different surgical, interventional, and systemic therapies, as well as their combinations.
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Affiliation(s)
- Christof M Sommer
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany, Heilbronn, Germany; Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany, Heilbronn, Germany
| | - Hans U Kauczor
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany, Heilbronn, Germany
| | - Philippe L Pereira
- Clinic for Radiology, Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Heilbronn, Germany
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Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma. Radiology 2016; 283:580-589. [PMID: 27820684 DOI: 10.1148/radiol.2016160572] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters. HAI consisted of infusions of oxaliplatin 40 mg/m2 for 2 hours, followed by 5-fluorouracil 800 mg/m2 for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. © RSNA, 2016.
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Affiliation(s)
- Xiaodong Wang
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jungang Hu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Guang Cao
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xu Zhu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Yong Cui
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xinqiang Ji
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xuan Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Renjie Yang
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Hui Chen
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Haifeng Xu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Peng Liu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jian Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jie Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Chunyi Hao
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Baocai Xing
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Lin Shen
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
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Lu CD, Wang K, Zhang CZ, Zhou FG, Guo WX, Wu MC, Cheng SQ. Outcomes of intrahepatic cholangiocarcinoma with portal vein tumor thrombus following hepatic resection. J Gastroenterol Hepatol 2016; 31:1330-5. [PMID: 26856257 DOI: 10.1111/jgh.13309] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 01/27/2016] [Accepted: 01/28/2016] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND AIM Portal vein tumor thrombus (PVTT) is not commonly used in the treatment of intrahepatic cholangiocarcinoma (ICC), and its impact on the prognosis of ICC is unclear. We aimed to assess the outcomes of ICC with or without PVTT after hepatic resection. METHODS From January 2000 to December 2005, the data from all consecutive patients with ICC who underwent hepatic resection at our hospital were retrospectively analyzed. According to the Cheng's PVTT Classification (types I-IV), we compared the survival outcomes of ICC patients (with or without PVTT) and prognosis of patients with ICC with different types of PVTT. RESULTS Three hundred and three patients with ICC were enrolled in this study (59 with PVTT). The incidence of PVTT was 19.4% (59/303). The median survival times were 12.68 and 28.91 months for ICC patients with and without PVTT, respectively (P < 0.001). The multivariate analysis demonstrated that PVTT (hazard ratio [HR] 1.783; confidence interval 95% [1.279; 2.487]) was an independent risk factor for overall survival. Patients with type I PVTT exhibited significantly better survival than those with types II and III PVTT. CONCLUSION The ICC patients with PVTT exhibit a poorer prognosis compared with ICC patients without PVTT after hepatic resection.
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Affiliation(s)
- Chong De Lu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Cun Zhen Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fei Guo Zhou
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei Xing Guo
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Meng Chao Wu
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu Qun Cheng
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma. Gastroenterol Res Pract 2016; 2016:8732521. [PMID: 26966431 PMCID: PMC4758109 DOI: 10.1155/2016/8732521] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 12/20/2015] [Indexed: 12/19/2022] Open
Abstract
Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237.
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Simo KA, Halpin LE, McBrier NM, Hessey JA, Baker E, Ross S, Swan RZ, Iannitti DA, Martinie JB. Multimodality treatment of intrahepatic cholangiocarcinoma: A review. J Surg Oncol 2016; 113:62-83. [DOI: 10.1002/jso.24093] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 10/31/2015] [Indexed: 02/06/2023]
Affiliation(s)
- Kerri A. Simo
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Laura E. Halpin
- Department of Surgery; University of Toledo Medical College; Toledo Ohio
| | - Nicole M. McBrier
- Hepatobiliary and Pancreas Surgery; ProMedica Health System; Toledo Ohio
- ProMedica Cancer Institute; ProMedica Health System; Toledo Ohio
| | | | - Erin Baker
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Samuel Ross
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - Ryan Z. Swan
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - David A. Iannitti
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
| | - John B. Martinie
- Hepatobiliary and Pancreas Surgery; Carolinas Medical Center; Charlotte North Carolina
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Yang L, Shan J, Shan L, Saxena A, Bester L, Morris DL. Trans-arterial embolisation therapies for unresectable intrahepatic cholangiocarcinoma: a systematic review. J Gastrointest Oncol 2015; 6:570-88. [PMID: 26487951 DOI: 10.3978/j.issn.2078-6891.2015.055] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Unresectable intrahepatic cholangiocarcinoma (ICC) portends a poor prognosis despite standard systemic treatments which confer minimal survival benefits and significant adverse effects. This study aimed to assess clinical outcomes, complications and prognostic factors of TAE therapies using chemotherapeutic agents or radiation. METHODS A literature search and article acquisition was conducted on PubMed (MEDLINE), OVID (MEDLINE) and EBSCOhost (EMBASE). Original articles published after January 2000 on trans-arterial therapies for unresectable ICC were selected using strict eligibility criteria. Radiological response, overall survival, progression-free survival, safety profile, and prognostic factors for overall survival were assessed. Quality appraisal and data tabulation were performed using pre-determined forms. Results were synthesized by narrative review and quantitative analysis. RESULTS Twenty articles were included (n=929 patients). Thirty three percent of patients presented with extrahepatic metastases. After treatment, the average rate of complete and partial radiological response was 10% and 22.2%, respectively. Overall median survival time was 12.4 months with a median 30-day mortality and 1-year survival rate of 0.6% and 53%, respectively. Acute treatment toxicity (within 30 days) was reported in 34.9% of patients, of which 64.3% were mild to moderate in severity. The most common clinical toxicities were abdominal pain, nausea and vomiting, and fatigue. Multiplicity, localization and vascularity of the tumor may predict worse overall survival. CONCLUSIONS Trans-arterial therapies are safe and effective treatment options which should be considered routinely for unresectable ICC. Consistent and standardized methodology and data collection is required to facilitate a meta-analysis. Randomized controlled trials will be valuable in the future.
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Affiliation(s)
- Linda Yang
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
| | - Jocelyn Shan
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
| | - Leonard Shan
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
| | - Akshat Saxena
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
| | - Lourens Bester
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
| | - David L Morris
- 1 Melbourne Medical School, The University of Melbourne, Victoria, Australia ; 2 Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ; 3 Department of Surgery, St George Hospital, Kogarah, New South Wales, Australia ; 4 Department of Radiology, School of Medicine, University of Notre Dame, Darlinghurst, New South Wales, Australia
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Abstract
Cholangiocarcinoma is a rare malignancy that arises from epithelial cells of the biliary system. Its desmoplastic histology and the heterogeneity of its presentation have contributed to its poor prognosis, with limited therapeutic options previously available. However, recent advances using locoregional therapy may expand the treatment arsenal used to manage this resistant malignancy. Although surgical resection has previously been reserved for relatively few patients because of inadequate hepatic reserve, portal vein embolization can induce contralateral hepatic lobe hypertrophy to increase the number of patients eligible for resection. For unresectable cases, both transarterial chemoembolization and yttrium-90 radioembolization have shown effectiveness in controlling tumor growth and prolonging survival.
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Abstract
Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. Most patients with hepatic malignancies are not candidates for curative surgical intervention, thereby warranting exploration of alternative means of treatment that preserves quality of life while providing clinical benefit. Herein, the data for intra-arterial chemoinfusion, transarterial chemoembolization, drug-eluting beads, and radioembolization are discussed in the setting of malignancies within the liver; outcome data relating to survival, time-to-progression, time-to-recurrence, and adverse events are presented. Further data regarding different treatment paradigms for hepatocellular carcinoma, metastatic colorectal carcinoma, neuroendocrine tumours, and intrahepatic cholangiocarcinoma are also provided. In light of these and forthcoming data, transarterial therapies seem to offer a viable treatment pathway for select populations of patients.
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Seidensticker R, Ricke J, Seidensticker M. Integration of chemoembolization and radioembolization into multimodal treatment of cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29:319-32. [PMID: 25966431 DOI: 10.1016/j.bpg.2015.02.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 02/07/2015] [Indexed: 02/07/2023]
Abstract
Over the last decade radioembolization and transarterial chemoembolization have been shown to be effective in unresectable intrahepatic cholangiocellular carcinoma. Unfortunately, up to now the evidence is not high with most of the conclusions drawn from single center retrospective analyses with small sample sizes treated in the salvage situation. However, the results are promising and suggest a survival benefit in the treatment of unresectable cholangiocellular carcinoma, even in an advanced stage with extrahepatic disease. In the following, available results of the treatment of unresectable cholangiocellular carcinoma by radioembolization and transarterial chemoembolization will be summarized. Special attention will be given to prognostic factors and efficacy as measured by response criteria. The potential integration of these therapies into multimodal treatment concepts will be discussed with focus on the intensification of therapy and a staged concept of therapy.
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Affiliation(s)
- Ricarda Seidensticker
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany.
| | - Jens Ricke
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany
| | - Max Seidensticker
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany
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Bergeat D, Sulpice L, Rayar M, Edeline J, Merdignac A, Meunier B, Boucher E, Boudjema K. Extended liver resections for intrahepatic cholangiocarcinoma: Friend or foe? Surgery 2015; 157:656-65. [DOI: 10.1016/j.surg.2014.11.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 10/26/2014] [Accepted: 11/17/2014] [Indexed: 12/27/2022]
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Intraarterial 5-fluorouracil and interferon therapy is safe and effective for nonresectable biliary tract adenocarcinoma. Hepatol Int 2015; 9:142-8. [PMID: 25788388 DOI: 10.1007/s12072-014-9583-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 09/09/2014] [Indexed: 10/24/2022]
Abstract
PURPOSE The prognosis in advanced biliary carcinoma has remained poor. The purpose of this study was to investigate the efficacy of intraarterial 5-fluorouracil and interferon therapy against unresectable biliary carcinoma. METHODS Patients with unresectable biliary carcinoma with performance status 0 or 1 were enrolled between January 2002 and September 2012. They received pegylated interferon-α 2a and intraarterial 5-FU every 4 weeks. The therapy was either terminated at the end of the first cycle for the patients with progressive disease or continued for at least three cycles. Patients' characteristics (physical, laboratory and radiographic) at the time of starting intraarterial 5-FU therapy were investigated. The relationship between the patients' characteristics and outcome, i.e., survival time and radiographic therapeutic evaluation of patients, was statistically analyzed. RESULTS Tumor sites were the intrahepatic bile ducts in 23 patients and gallbladder in 2 patients. Previous treatment had been administered in ten patients. The overall response rate was 24% (6 partial responses in 25 patients). Stable disease was observed in 13 patients. The median overall survival was 358 days. Among the six partial responses, three patients received surgery, and one patient received radiofrequency ablation because clinical downstaging was obtained. The treatment was well tolerated. The survival analyses revealed that two factors (serum albumin ≥ 3.5 and hypovascular tumor) were significantly associated with overall survival. CONCLUSIONS Combination therapy with 5-FU and interferon-α was safe and may improve the prognosis of advanced biliary carcinomas.
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Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer. Cancer Chemother Pharmacol 2015; 75:805-12. [PMID: 25687990 DOI: 10.1007/s00280-015-2704-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 02/11/2015] [Indexed: 10/24/2022]
Abstract
PURPOSE S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC. METHODS BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m(2) on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m(2) on days 1-14) until disease progression occurred. RESULTS Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33%) patients. Among six patients who were treated with 60 mg/m(2) S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m(2) S-1. Two of the three patients who were treated with 80 mg/m(2) S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m(2) was defined as the MTD of S-1. CONCLUSION The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.
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Al-Adra DP, Gill RS, Axford SJ, Shi X, Kneteman N, Liau SS. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:120-7. [PMID: 25449754 PMCID: PMC4316196 DOI: 10.1016/j.ejso.2014.09.007] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Revised: 07/23/2014] [Accepted: 09/22/2014] [Indexed: 12/12/2022]
Abstract
Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.
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Affiliation(s)
- D P Al-Adra
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - R S Gill
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - S J Axford
- St. George's University, University Centre, Grenada, West Indies
| | - X Shi
- Center for the Advancement of Minimally Invasive Surgery, Royal Alexandra Hospital, Edmonton, AB, Canada
| | - N Kneteman
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - S-S Liau
- Hepatopancreatobiliary Surgical Unit, University Department of Surgery, Addenbrooke's Hospital, University of Cambridge, United Kingdom.
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Abstract
Over the last decade, transarterial therapies have gained worldwide acceptance as standard of care for inoperable primary liver cancer. Survival times after transarterial chemoembolization (TACE) continue to improve as the technique and selection criteria are refined. Transarterial treatments, frequently provided in an outpatient setting, are now safely and effectively being applied to patients with even advanced malignancy or partially decompensated cirrhosis. In the coming years, newer transarterial therapies such as radiation segmentectomy, boosted-transarterial radioembolzation, combined TACE-ablation, TACE-portal vein embolization, and transarterial infusion of cancer-specific metabolic inhibitors promise to continue improving survival and quality of life.
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