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Zhang J, Dong W, Liu W, Fu J, Liao T, Li Y, Huo L, Jia N. Preoperative evaluation of MRI features and inflammatory biomarkers in predicting microvascular invasion of combined hepatocellular cholangiocarcinoma. Abdom Radiol (NY) 2024; 49:710-721. [PMID: 38112787 PMCID: PMC10909765 DOI: 10.1007/s00261-023-04130-6] [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: 08/24/2023] [Revised: 11/07/2023] [Accepted: 11/12/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA. METHODS This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance. RESULTS Multivariable logistic regression analysis identified four variables significantly associated with MVI (p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719-0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model. CONCLUSION Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients.
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Affiliation(s)
- Juan Zhang
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wanmin Liu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiazhao Fu
- Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Tian Liao
- Department of Ultrasound, Changsha Hospital of Traditional Chinese Medicine, Changsha, China
| | - Yinqiao Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lei Huo
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
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Zhang YQ, Wang K, Feng JK, Yuan LY, Liang C, Xiang YJ, Wang X, Mao FF, Cheng SQ. Camrelizumab plus gemcitabine and oxaliplatin for the treatment of advanced intrahepatic cholangiocarcinoma: a bi-centric observational retrospective study. Front Oncol 2023; 13:1101038. [PMID: 37197414 PMCID: PMC10183568 DOI: 10.3389/fonc.2023.1101038] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 04/14/2023] [Indexed: 05/19/2023] Open
Abstract
Background Immune checkpoint inhibitor (ICI), coupled with systemic chemotherapy, may enhance the clinical benefit of cancer by potentiating antitumor immunity, but its efficacy and safety are not clear in advanced intrahepatic cholangiocarcinoma (ICC). This study aims to assess the efficacy and safety of camrelizumab plus gemcitabine and oxaliplatin (GEMOX) for the treatment of advanced ICC in the real world. Methods Advanced ICC patients receiving at least one session of camrelizumab plus GEMOX combination treatment from March 2020 to February 2022 at two high-volume centers were considered eligible. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The primary endpoint was objective response rate (ORR), disease control rate (DCR), time to response (TTR), and duration of response (DOR). The secondary end points included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs). Results 30 eligible ICC patients were enrolled and analyzed in this observational retrospective study. The median follow-up time was 24.0 (21.5-26.5) months. The ORR and DCR were 40% and 73.3%, respectively. The median TTR was 2.4 months and the median DOR was 5.0 months. The median PFS and OS were 7.5 months and 17.0 months, respectively. The most common TRAEs were fever (83.3%), fatigue (73.3%), and nausea (70%). Of all TRAEs, thrombocytopenia, and neutropenia were the most frequent severe AE (both 10%). Conclusion The combination of camrelizumab and GEMOX is a potentially efficacious and safe treatment modality for advanced ICC patients. Potential biomarkers are needed to identify patients who might benefit from this treatment option.
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Affiliation(s)
- Yu-Qing Zhang
- Cancer Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jin-Kai Feng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lu-Yun Yuan
- Cancer Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chao Liang
- Department of Hepatobiliary Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan-Jun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xu Wang
- Cancer Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fei-Fei Mao
- Tongji University Cancer Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shu-Qun Cheng
- Cancer Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- *Correspondence: Shu-Qun Cheng,
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Zhou C, Lu X, Wang Y, Qian X, Yang C, Zeng M. Histopathological components correlated with MRI features and prognosis in combined hepatocellular carcinoma-cholangiocarcinoma. Eur Radiol 2022; 32:6702-6711. [PMID: 35976399 DOI: 10.1007/s00330-022-09065-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 06/13/2022] [Accepted: 07/26/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES To distinguish MR features according to different proportions of the histopathological hepatocellular carcinoma (HCC) component and to investigate whether the proportion of the HCC component can predict the prognosis of patients with cHCC-CCA. METHODS The study enrolled 106 cHCC-CCA patients confirmed by histopathology. The MR imaging features and clinicopathological findings were retrospectively evaluated and compared between two subgroups with different proportions of the HCC component. The recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, whether the proportion of the HCC component was a predictor of RFS and OS was investigated using Cox regression analyses. RESULTS The Liver Imaging Reporting and Data System (LI-RADS) category 4/5 was more prevalent in cHCC-CCAs with an HCC component > 50% (odds ratio (OR) = 5.559, p = 0.018), 70% (OR = 4.031, p = 0.008), and 90% (OR = 6.282, p = 0.012) than in those with an HCC component ≤ 50%, 70%, and 90%, respectively. In addition, cHCC-CCAs with an HCC component > 70% (HR: 0.241, p = 0.023) had a better OS prognosis than those with an HCC component ≤ 70%. CONCLUSIONS cHCC-CCAs categorized as LR-4/5 are mainly composed of HCC component, and cHCC-CCAs with an HCC component > 70% are associated with better OS than those with an HCC component ≤ 70%. These findings suggest that the proportion of HCC or CCA component can predict the prognosis of cHCC-CCA patients. KEY POINTS • cHCC-CCAs categorized as LR-4/5 are mainly composed of HCC component. • cHCC-CCAs with an HCC component > 70% are associated with better OS than those with an HCC component ≤ 70%.
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Affiliation(s)
- Changwu Zhou
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xin Lu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xianling Qian
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, Shanghai, China. .,Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Zhou YW, Li QF, Chen YY, Wang K, Pu D, Chen XR, Li CH, Jiang L, Wang Y, Li Q, Yang Y, Gou HF, Bi F, Liu JY, Chen Y, Qiu M. Clinicopathologic features, treatment, survival, and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1559-1566. [PMID: 35115213 DOI: 10.1016/j.ejso.2022.01.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/07/2021] [Accepted: 01/23/2022] [Indexed: 02/05/2023]
Abstract
PURPOSE The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC. METHODS Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort. RESULTS A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model. CONCLUSION CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.
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Affiliation(s)
- Yu-Wen Zhou
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Qing-Fang Li
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Yue-Yun Chen
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China
| | - Kai Wang
- Institute for Emergency Medicine and Disaster Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, China
| | - Dan Pu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Rong Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Chun-Hong Li
- Department of Oncology, Suining Central Hospital, Suining, China
| | - Li Jiang
- Department of Abdominal Oncology, Sichuan Cancer Hospital, Chengdu, China
| | - Yan Wang
- Department of Oncology, The First People's Hospital of Long Quan Yi District, Chengdu, China
| | - Qiu Li
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yu Yang
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Hong-Feng Gou
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Feng Bi
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China
| | - Ji-Yan Liu
- Department of Biotherapy, Cancer Center, West China Hospital of Sichuan University, Chengdu, China; Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, China.
| | - Ye Chen
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
| | - Meng Qiu
- Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
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Yang Z, Shi G. Survival outcomes of combined hepatocellular-cholangiocarcinoma compared with intrahepatic cholangiocarcinoma: A SEER population-based cohort study. Cancer Med 2021; 11:692-704. [PMID: 34862762 PMCID: PMC8817088 DOI: 10.1002/cam4.4474] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/04/2021] [Accepted: 11/09/2021] [Indexed: 12/13/2022] Open
Abstract
Background Combined hepatocellular‐cholangiocarcinoma (CHC) is a heterogeneous group of primary liver cancers characterized by the coexistence of both hepatic and biliary cellular contents. The aim of this study was to compare CHC and intrahepatic cholangiocarcinoma (ICC) and investigate the treatment and survival of patients with CHC. Methods Data on CHC and ICC, including clinicopathological characteristics, treatments, and survival outcomes were extracted from the SEER database between 2004 and 2016. Univariate and multivariate analyses of all data were performed to identify the risk factors associated with survival outcomes. The overall survival (OS) rates of CHC patients who underwent hepatic resection (HR) or liver transplantation (LT) were also assessed before and after propensity score matching. Results A total of 1066 consecutive patients who had been diagnosed with CHC (n = 286) or ICC (n = 780) were identified. The mean age of the CHC cohort was 60.8±10.7 years old. Among the CHC group, a large proportion of the patients were men and of White ethnicity (73.1% and 71.3%, respectively). The majority of tumors were poorly differentiated (37.8%), while the most common AJCC stage at presentation was stage I (31.4%). Multivariable analysis of all CHC patients revealed that only tumor size, M1 stage, AJCC stage IIIC, AJCC stage IV, surgery, and chemotherapy were significantly associated with OS. The OS was comparable with the ICC in the initial 36 months and better in the subsequent follow‐up after treatment. Surgery was associated with better survival outcomes, whether in the early or advanced stages. Regarding the specific types of surgery, the OS rates were similar in selected patients following HR or LT. Conclusion In patients with CHC, surgical intervention resulted in better long‐term survival outcomes than nonsurgical treatments. The OS rate of CHC patients compared with that of ICC patients was discriminated before and after a 3‐year follow‐up.
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Affiliation(s)
- Zhen Yang
- Department of Hepatopancreatobiliary Surgery, Qingdao Municipal Hospital, Qingdao University, Qingdao, P.R. China
| | - Guangjun Shi
- Department of Hepatopancreatobiliary Surgery, Qingdao Municipal Hospital, Qingdao University, Qingdao, P.R. China
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Nguyen CT, Caruso S, Maille P, Beaufrère A, Augustin J, Favre L, Pujals A, Boulagnon-Rombi C, Rhaiem R, Amaddeo G, di Tommaso L, Luciani A, Regnault H, Brustia R, Scatton O, Charlotte F, Brochériou I, Sommacale D, Soussan P, Leroy V, Laurent A, Le VK, Ta VT, Trinh HS, Tran TL, Gentien D, Rapinat A, Nault JC, Allaire M, Mulé S, Zucman-Rossi J, Pawlotsky JM, Tournigand C, Lafdil F, Paradis V, Calderaro J. Immune profiling of combined hepatocellular-cholangiocarcinoma reveals distinct subtypes and activation of gene signatures predictive of response to immunotherapy. Clin Cancer Res 2021; 28:540-551. [PMID: 34785581 DOI: 10.1158/1078-0432.ccr-21-1219] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/18/2021] [Accepted: 11/09/2021] [Indexed: 11/16/2022]
Abstract
Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of immunohistochemical stainings. Genetic alterations were investigated using targeted next generation sequencing. Results: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an "Immune High" (IH) subtype (57% of the cases) and an "Immune Low" (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (p<0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. Conclusions: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intra-tumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.
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Affiliation(s)
- Cong Trung Nguyen
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Stefano Caruso
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
| | - Pascale Maille
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Aurélie Beaufrère
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
| | - Jérémy Augustin
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Loetitia Favre
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Anaïs Pujals
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Camille Boulagnon-Rombi
- Centre Hospitalier Universitaire de Reims, Service d'Anatomie et de Cytologie Pathologiques, Reims, France
| | - Rami Rhaiem
- Hôpital Robert Debré, Service de Chirurgie Digestive et Hépatobiliaire, Reims, France
| | - Giuliana Amaddeo
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Luca di Tommaso
- Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Alain Luciani
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Hélène Regnault
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Raffaele Brustia
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Olivier Scatton
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Frédéric Charlotte
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Isabelle Brochériou
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Daniele Sommacale
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Patrick Soussan
- Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Santé et de la Recherche Médicale (Inserm, UMR1135), Sorbonne Universités, Paris, France
| | - Vincent Leroy
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Alexis Laurent
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Van Ky Le
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Van To Ta
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Hong Son Trinh
- Department of Surgical Oncology, Vietduc Hospital, Hanoi, Vietnam
| | - Thi Lan Tran
- Department of Pathology, Hanoi Medical University, Hanoi, Vietnam
| | - David Gentien
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Audrey Rapinat
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Jean Charles Nault
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France
| | - Manon Allaire
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Hépatologie, Paris, France
| | - Sebastien Mulé
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Jessica Zucman-Rossi
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France
- Université Paris Descartes, Université Paris Diderot, Université Paris 13, France
| | - Jean-Michel Pawlotsky
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Christophe Tournigand
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Oncologie Médicale, Créteil, France
| | - Fouad Lafdil
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Institut Universitaire de France (IUF), Paris, France
| | - Valérie Paradis
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
- Université de Paris, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252, Paris, France
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France.
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
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Wang J, Li Z, Liao Y, Li J, Dong H, Peng H, Xu W, Fan Z, Gao F, Liu C, Liu D, Zhang Y. Prediction of Survival and Analysis of Prognostic Factors for Patients With Combined Hepatocellular Carcinoma and Cholangiocarcinoma: A Population-Based Study. Front Oncol 2021; 11:686972. [PMID: 34336671 PMCID: PMC8322675 DOI: 10.3389/fonc.2021.686972] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/28/2021] [Indexed: 12/18/2022] Open
Abstract
Background Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is an uncommon subtype of primary liver cancer. Because of limited epidemiological data, prognostic risk factors and therapeutic strategies for patients with CHC tend to be individualized. This study aimed to identify independent prognostic factors and develop a nomogram-based model for predicting the overall survival (OS) of patients with CHC. Methods We recruited eligible individuals from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 and randomly divided them into the training or verification cohort. Univariate and multivariate analyses were performed to identify independent variables associated with OS. Based on multivariate analysis, the nomogram was established, and its prediction performance was evaluated using the consistency index (C-index) and calibration curve. Results In total, 271 patients with CHC were included in our study. The median OS was 14 months, and the 1-, 3-, and 5-year OS rates were 52.3%, 27.1%, and 23.3%, respectively. In the training cohort, multivariate analysis showed that the pathological grade (hazard ratio [HR], 1.26; 95% confidence interval [CI]: 0.96–1.66), TNM stage (HR, 1.21; 95% CI: 1.02 - 1.44), and surgery (HR, 0.26; 95% CI: 0.17 - 0.40) were independent indicators of OS. The nomogram-based model related C-indexes were 0.76 (95% CI: 0.72 - 0.81) and 0.72 (95% CI: 0.66 - 0.79) in the training and validation cohorts, respectively. The calibration of the nomogram showed good consistency of 1-, 3-, and 5-year OS rates between the actual observed survival and predicted survival in both cohorts. The TNM stage (HR, 1.23; 95% CI: 1.01 - 1.49), and M stage (HR, 1.87; 95% CI: 1.14 3.05) were risk factors in the surgical treatment group. Surgical resection and liver transplantation could significantly prolong the survival, with no statistical difference observed. Conclusions The pathological grade, TNM stage, and surgery were independent prognostic factors for patients with CHC. We developed a nomogram model, in the form of a static nomogram or an online calculator, for predicting the OS of patients with CHC, with a good predictive performance.
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Affiliation(s)
- Jitao Wang
- School of Medicine, Southeast University, Nanjing, China.,Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Zhi Li
- Department of Infection Management, Xingtai General Hospital of North China Healthcare Group, Xingtai, China
| | - Yong Liao
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Jinlong Li
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Hui Dong
- School of Medicine, Southeast University, Nanjing, China
| | - Hao Peng
- School of Medicine, Southeast University, Nanjing, China
| | - Wenjing Xu
- School of Medicine, Southeast University, Nanjing, China
| | - Zhe Fan
- School of Medicine, Southeast University, Nanjing, China
| | - Fengxiao Gao
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Chengyu Liu
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Dengxiang Liu
- Xingtai Institute of Cancer Control, Xingtai People's Hospital, Xingtai, China
| | - Yewei Zhang
- School of Medicine, Southeast University, Nanjing, China.,Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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8
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Elevated neutrophil-to-lymphocyte ratio and predominance of intrahepatic cholangiocarcinoma prediction of poor hepatectomy outcomes in patients with combined hepatocellular-cholangiocarcinoma. PLoS One 2020; 15:e0240791. [PMID: 33306714 PMCID: PMC7732129 DOI: 10.1371/journal.pone.0240791] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 10/03/2020] [Indexed: 12/29/2022] Open
Abstract
Objectives Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC. Methods We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival. Results Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival. Conclusions Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.
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9
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Zhang F, Lu CD, Zhang XP, Chen ZH, Zhong CQ, Hu YR, Wei XB, Zhou B, Wang K, Chai ZT, Wu MC, Lau WY, Cheng SQ. The impact of portal vein tumor thrombus on long-term survival after liver resection for primary hepatic malignancy. HPB (Oxford) 2020; 22:1025-1033. [PMID: 31732465 DOI: 10.1016/j.hpb.2019.10.2439] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 10/15/2019] [Accepted: 10/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.
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Affiliation(s)
- Fan Zhang
- The Medical College of Soochow University, Jiangsu, China; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chong-De Lu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Department of Hepatobiliary and Pancreatic Surgical Oncology, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Cheng-Qian Zhong
- LongYan First Hospital, Affiliated to Fujian Medical University, FuJian, China
| | - Yi-Ren Hu
- Department of General Surgery, Wenzhou People's Hospital, Zhejiang, China
| | - Xu-Biao Wei
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Bin Zhou
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan Y Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Shu-Qun Cheng
- The Medical College of Soochow University, Jiangsu, China; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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10
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Radiological features and outcomes of combined hepatocellular-cholangiocarcinoma in patients undergoing surgical resection. J Formos Med Assoc 2020; 119:125-133. [DOI: 10.1016/j.jfma.2019.02.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/01/2019] [Accepted: 02/23/2019] [Indexed: 12/14/2022] Open
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11
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Song P, Midorikawa Y, Nakayama H, Higaki T, Moriguchi M, Aramaki O, Yamazaki S, Aoki M, Teramoto K, Takayama T. Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection. Cancer Med 2019; 8:5862-5871. [PMID: 31407490 PMCID: PMC6792494 DOI: 10.1002/cam4.2495] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/30/2019] [Accepted: 08/01/2019] [Indexed: 12/12/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.
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Affiliation(s)
- Peipei Song
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Hisashi Nakayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Aramaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Masaru Aoki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Kenichi Teramoto
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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12
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Spolverato G, Bagante F, Tsilimigras D, Ejaz A, Cloyd J, Pawlik TM. Management and outcomes among patients with mixed hepatocholangiocellular carcinoma: A population-based analysis. J Surg Oncol 2018; 119:278-287. [PMID: 30554420 DOI: 10.1002/jso.25331] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 11/23/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND We sought to define the management of mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) as well as characterize short- and long-term outcomes of patients with mixed HCC-ICC. METHODS Patients diagnosed with HCC-ICC, HCC, or ICC between 2004 and 2015 were identified from the National Cancer Data Base using the International Classification of Diseases for Oncology codes. Short- and long-term outcomes were assessed using univariate and multivariate analyses. RESULTS Among 174 454 patients, 86.8% had HCC, 12.1% ICC, and 1.1% HCC-ICC. The incidence of lymphadenectomy was 55.6% among ICC patients vs 15.1% and 34.2% for HCC and HCC-ICC patients, respectively (P < 0.001). A 90-day mortality was comparable among patients with HCC (9.1%), ICC (8.8%), and HCC-ICC (10.5%) (all P > 0.2). While 42.0% of ICC patients received adjuvant chemotherapy, adjuvant chemotherapy among HCC and HCC-ICC patients was 13.1% and 27.4%, respectively (P < 0.001). A 5-year survival was 43.5% (95% CI, 42.5-44.5), 33.3% (95% CI, 31.4-35.3), 34.4% (95% CI, 29.1-39.8) for HCC, ICC, and HCC-ICC patients, respectively. CONCLUSION Patients who underwent resection of mixed HCC-ICC had a prognosis that was comparable to ICC, yet worse than HCC. Utilization of lymphadenectomy and adjuvant therapy were low. HCC-ICC remains a rare disease with a guarded prognosis that should be treated in a multidisciplinary setting.
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Affiliation(s)
- Gaya Spolverato
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Fabio Bagante
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.,Department of Surgery, University of Verona, Verona, Italy
| | - Diamantis Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Aslam Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jordan Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
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13
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Ma KW, Chok KSH, She WH, Cheung TT, Chan ACY, Dai WC, Fung JYY, Lo CM. Hepatocholangiocarcinoma/intrahepatic cholangiocarcinoma: are they contraindication or indication for liver transplantation? A propensity score-matched analysis. Hepatol Int 2018; 12:167-173. [PMID: 29450868 DOI: 10.1007/s12072-018-9847-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/29/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Uncommon primary hepatic malignancies such as intrahepatic cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally considered contraindications for liver transplantation(LT), and studies comparing the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce. OBJECTIVE To compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a propensity score-matched population. METHOD This is a retrospective study from 1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC-CC in the surgical specimens were included. All patients had either hepatectomy or LT with curative intent. Factors associated with survival were identified with multivariate analysis using cox-regression model. Propensity score-matched analysis was performed. RESULT There were 181 patients diagnosed to have ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172 received hepatectomy. The median follow-up period was 27.5 months. The median age was 60 years (range 3-86); Hepatitis B and C carrier status was found in 48.1 and 2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of them had solitary tumor. Microvascular invasion was present in 47% of the patients. After propensity score matching, there were 54 (9 in LT and 45 in LR group) patients for analysis. Cox-regression analysis showed that early AJCC (7th) staging and LT were the independent factors associated with overall survival. Patients in the LT group had significantly better overall survival (5-year OS 77.8 vs 36.6%, log-rank p = 0.013). CONCLUSION ICC/HCC-CC are uncommon tumors with poor long-term oncological outcomes despite curative hepatectomy. Liver transplantation might be a better treatment option for patients with early ICC/HCC-CC.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - James Yan Yue Fung
- Department of Medicine, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
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14
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Salimon M, Prieux-Klotz C, Tougeron D, Hautefeuille V, Caulet M, Gournay J, Matysiak-Budnik T, Bennouna J, Tiako Meyo M, Lecomte T, Zaanan A, Touchefeu Y. Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study. Br J Cancer 2018; 118:325-330. [PMID: 29169182 PMCID: PMC5808029 DOI: 10.1038/bjc.2017.413] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 10/17/2017] [Accepted: 10/20/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. METHODS Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan-Meier method and prognostic factors by Log-rank test and Cox model. RESULTS Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 μmol l-1 (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS. CONCLUSIONS Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC.
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Affiliation(s)
- Maëva Salimon
- Institut des Maladies de l'appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France
| | - Caroline Prieux-Klotz
- Department of Gastroenterology and Oncology, Cochin University Hospital, Paris 75014, France
| | - David Tougeron
- Department of Gastroenterology, Poitiers University Hospital, Poitiers 86600, France
| | - Vincent Hautefeuille
- Amiens University Hospital, Department of Gastroenterology and Oncology, Amiens 80054, France
| | - Morgane Caulet
- Tours University Hospital, Department of Gastroenterology and Oncology, Tours 37000, France
| | - Jérôme Gournay
- Institut des Maladies de l'appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France
| | - Tamara Matysiak-Budnik
- Institut des Maladies de l'appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France
| | - Jaafar Bennouna
- Institut des Maladies de l'appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France
| | - Manuela Tiako Meyo
- Department of Gastroenterology and Digestive Oncology, Sorbonne Paris Cité, Paris Descartes University, Georges Pompidou European Hospital, Paris 75015, France
| | - Thierry Lecomte
- Tours University Hospital, Department of Gastroenterology and Oncology, Tours 37000, France
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, Sorbonne Paris Cité, Paris Descartes University, Georges Pompidou European Hospital, Paris 75015, France
| | - Yann Touchefeu
- Institut des Maladies de l'appareil Digestif, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44000, France
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15
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Ma KW, Chok KSH. Importance of surgical margin in the outcomes of hepatocholangiocarcinoma. World J Hepatol 2017; 9:635-641. [PMID: 28539991 PMCID: PMC5424293 DOI: 10.4254/wjh.v9.i13.635] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 03/14/2017] [Accepted: 04/06/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the significance of resection margin width in the management of hepatocholangiocarcinoma (HCC-CC). METHODS Data of consecutive patients who underwent hepatectomy for hepatic malignancies in the period from 1995 to 2014 were reviewed. Patients with pathologically confirmed HCC-CC were included for analysis. Demographic, biochemical, operative and pathological data were analyzed against survival outcomes. RESULTS Forty-two patients were included for analysis. The median age was 53.5 years. There were 29 males. Hepatitis B virus was identified in 73.8% of the patients. Most patients had preserved liver function. The median preoperative indocyanine green retention rate at 15 min was 10.2%. The median tumor size was 6.5 cm. Major hepatectomy was required in over 70% of the patients. Hepaticojejunostomy was performed in 6 patients. No hospital death occurred. The median hospital stay was 13 d. The median follow-up period was 32 mo. The 5-year disease-free survival and overall survival were 23.6% and 35.4% respectively. Multifocality was the only independent factor associated with disease-free survival [P < 0.001, odds ratio 4, 95% confidence interval (CI): 1.9-8.0]. In patients with multifocal tumor (n = 20), resection margin of ≥ 1 cm was associated with improved 1-year disease-free survival (40% vs 0%; log-rank, P = 0.012). CONCLUSION HCC-CC is a rare disease with poor prognosis. Resection margin of 1 cm or above was associated with improved survival outcome in patients with multifocal HCC-CC.
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Affiliation(s)
- Ka Wing Ma
- Ka Wing Ma, Department of Surgery, Queen Mary Hospital, Hong Kong, China
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16
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Garancini M, Goffredo P, Pagni F, Romano F, Roman S, Sosa JA, Giardini V. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transpl 2014; 20:952-9. [PMID: 24777610 DOI: 10.1002/lt.23897] [Citation(s) in RCA: 118] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 04/21/2014] [Indexed: 12/12/2022]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver cancer. Our aims were to analyze the demographic, clinical, and pathological characteristics of cHCC-CC at a population level and to investigate the effects of these features as well as different management strategies on the prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for 1988-2009. Data analyses were performed with chi-square tests, analyses of variance, Kaplan-Meier curves, and Cox proportional hazards regression. Four hundred sixty-five patients with cHCC-CC, 52,825 patients with hepatocellular carcinoma (HCC), and 7181 patients with cholangiocarcinoma (CC) were identified. cHCC-CC was more common in patients who were white, male, and older than 65 years. Treatment was more frequently nonsurgical/interventional. Patients with cHCC-CC, HCC, and CC had 5-year overall survival (OS) and disease-specific survival rates of 10.5%, 11.7%, and 5.7% (P < 0.001) and 17.8%, 21.0%, and 11.9% (P < 0.001), respectively. For cHCC-CC patients, an increasing invasiveness of the therapeutic approach was significantly associated with prolonged survival (P < 0.001). In a multivariate model, black race, a distant SEER stage, and a tumor size of 5.0 to 10.0 cm were independently associated with lower survival for cHCC-CC patients; a year of diagnosis after 1995 and surgical treatment with minor hepatectomy, major hepatectomy (MJH), or liver transplantation (LT) were independently associated with better survival for cHCC-CC patients. Patients diagnosed with cHCC-CC, HCC, and CC and treated with LT had 5-year OS rates of 41.1%, 67.0%, and 29.0%, respectively (P < 0.001). In conclusion, cHCC-CC patients appear to have intermediate demographic, clinical, and survival characteristics in comparison with HCC and CC patients. cHCC-CC patients undergoing LT showed inferior survival in comparison with HCC patients, and the role and indications for LT in cHCC-CC have yet to be defined. At this time, MJH may be considered the best therapeutic approach for such patients.
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Affiliation(s)
- Mattia Garancini
- Departments of General Surgery, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
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17
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Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma. Eur J Surg Oncol 2014; 40:976-81. [PMID: 24909336 DOI: 10.1016/j.ejso.2014.04.016] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 04/25/2014] [Accepted: 04/28/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas. METHODS We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009. RESULTS Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors. CONCLUSIONS Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.
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Intrahepatic Cholangiocarcinoma or Mixed Hepatocellular-Cholangiocarcinoma in Patients Undergoing Liver Transplantation. Ann Surg 2014; 259:944-52. [DOI: 10.1097/sla.0000000000000494] [Citation(s) in RCA: 126] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Kim SE, Lee HC, Shim JH, Park HJ, Kim KM, Kim PN, Shin YM, Yu ES, Chung YH, Suh DJ. Noninvasive diagnostic criteria for hepatocellular carcinoma in hepatic masses >2 cm in a hepatitis B virus-endemic area. Liver Int 2011; 31:1468-76. [PMID: 21745284 DOI: 10.1111/j.1478-3231.2011.02529.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Noninvasive criteria for diagnosing hepatocellular carcinoma (HCC) suggested by the American Association for the Study of Liver Diseases (AASLD) in 2005 consisted of serum α-fetoprotein (AFP) level >200 ng/ml or a typical enhancement pattern (arterial enhancement and portal/delayed washed out) on dynamic imaging of hepatic mass(es) >2 cm in a cirrhotic liver. AIMS To validate these criteria in a Korean population and to evaluate whether these criteria are applicable to patients without cirrhosis at a high risk of developing HCC. METHODS We prospectively investigated 206 consecutive patients with hepatic mass(es) >2 cm who underwent biopsy or surgical resection. Patients were evaluated by four-phase dynamic computed tomography (CT) and by assays of serum AFP concentrations at baseline. Patients were classified according to the presence of risk factors or cirrhosis, and the diagnostic accuracy of each test was determined. RESULTS The positive predictive values (PPV) of typical CT findings or serum AFP >200 ng/ml were 97.8% in cirrhotic patients, 89.6% in high-risk patients without cirrhosis and 82.4% in low-risk patients. The PPVs of typical CT findings alone in these groups were 98.8, 97.6 and 87.5% respectively. In high-risk patients without cirrhosis, the addition of serum AFP levels to typical CT findings minimally increased the diagnostic sensitivity from 81.6 to 87.8% but reduced the PPV from 97.6 to 89.6%. CONCLUSIONS Serum AFP concentration is not a suitable diagnostic criterion for HCC. Typical CT findings can be used to diagnose HCC >2 cm both in cirrhotic patients and in high-risk patients without cirrhosis.
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Affiliation(s)
- Sung Eun Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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