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Sun Y, Jiang W, Duan R, Guan L. Research progress and prospect of postoperative adjuvant therapy for resectable intrahepatic cholangiocarcinoma. Front Pharmacol 2024; 15:1432603. [PMID: 39170710 PMCID: PMC11335543 DOI: 10.3389/fphar.2024.1432603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 07/29/2024] [Indexed: 08/23/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver, following hepatocellular carcinoma (HCC). Surgical resection remains the only potentially curative treatment for ICC. However, due to its high malignancy and propensity for postoperative recurrence, the prognosis for ICC is generally poor, and there is currently little standardized approach for adjuvant therapy following curative surgery. This article aims to explore adjuvant treatment strategies for ICC post-curative surgery by reviewing retrospective studies and clinical trials conducted in recent years. The analysis focuses on the effectiveness, challenges, and potential developments in the management of ICC post-surgery, considering the high recurrence rates and the need for improved therapeutic approaches to enhance patient outcomes. Additionally, we discuss the various types of adjuvant treatments that have been explored, including chemotherapy, radiation therapy, and targeted therapies. The goal is to provide a comprehensive overview of the current landscape and highlight promising directions for future research to improve survival and quality of life for ICC patients.
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Affiliation(s)
| | | | | | - Lianyue Guan
- Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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Kendall T, Overi D, Guido M, Braconi C, Banales J, Cardinale V, Gaudio E, Groot Koerkamp B, Carpino G. Recommendations on maximising the clinical value of tissue in the management of patients with intrahepatic cholangiocarcinoma. JHEP Rep 2024; 6:101067. [PMID: 38699072 PMCID: PMC11060959 DOI: 10.1016/j.jhepr.2024.101067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 05/05/2024] Open
Abstract
Background & Aims Patients with intrahepatic cholangiocarcinoma can now be managed with targeted therapies directed against specific molecular alterations. Consequently, tissue samples submitted to the pathology department must produce molecular information in addition to a diagnosis or, for resection specimens, staging information. The pathologist's role when evaluating these specimens has therefore changed to accommodate such personalised approaches. Methods We developed recommendations and guidance for pathologists by conducting a systematic review of existing guidance to generate candidate statements followed by an international Delphi process. Fifty-nine pathologists from 28 countries in six continents rated statements mapped to all elements of the specimen pathway from receipt in the pathology department to authorisation of the final written report. A separate survey of 'end-users' of the report including surgeons, oncologists, and gastroenterologists was undertaken to evaluate what information should be included in the written report to enable appropriate patient management. Results Forty-eight statements reached consensus for inclusion in the guidance including 10 statements about the content of the written report that also reached consensus by end-user participants. A reporting proforma to allow easy inclusion of the recommended data points was developed. Conclusions These guiding principles and recommendations provide a framework to allow pathologists reporting on patients with intrahepatic cholangiocarcinoma to maximise the informational yield of specimens required for personalised patient management. Impact and Implications Biopsy or resection lesional tissue from intrahepatic cholangiocarcinoma must yield information about the molecular abnormalities within the tumour that define suitability for personalised therapies in addition to a diagnosis and staging information. Here, we have developed international consensus guidance for pathologists that report such cases using a Delphi process that sought the views of both pathologists and 'end-users of pathology reports. The guide highlights the need to report cases in a way that preserves tissue for molecular testing and emphasises that reporting requires interpretation of histological characteristics within the broader clinical and radiological context. The guide will allow pathologists to report cases of intrahepatic cholangiocarcinoma in a uniform manner that maximises the value of the tissue received to facilitate optimal multidisciplinary patient management.
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Affiliation(s)
- Timothy Kendall
- University of Edinburgh Centre for Inflammation Research and Edinburgh Pathology, University of Edinburgh, Edinburgh, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Guido
- Department of Medicine, DIMED, University of Padua, Padua, Italy
| | - Chiara Braconi
- School of Cancer Sciences, University of Glasgow, CRUK Scotland Cancer Centre, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Jesus Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, CIBERehd and University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Vincenzo Cardinale
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Guido Carpino
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
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Bragazzi MC, Venere R, Ribichini E, Covotta F, Cardinale V, Alvaro D. Intrahepatic cholangiocarcinoma: Evolving strategies in management and treatment. Dig Liver Dis 2024; 56:383-393. [PMID: 37722960 DOI: 10.1016/j.dld.2023.08.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/07/2023] [Accepted: 08/21/2023] [Indexed: 09/20/2023]
Abstract
Intrahepatic cholangiocarcinoma is the second most frequent primary liver cancer after hepatocellular carcinoma. According to International Classification of Diseases-11 (ICD-11), intrahepatic cholangiocarcinoma is identified by a specific diagnostic code, different with respect to perihilar-CCA or distal-CCA. Intrahepatic cholangiocarcinoma originates from intrahepatic small or large bile ducts including the second-order bile ducts and has a silent presentation that combined with the highly aggressive nature and refractoriness to chemotherapy contributes to the alarming increasing incidence and mortality. Indeed, at the moment of the diagnosis, less than 40% of intrahepatic cholangiocarcinoma are suitable of curative surgical therapy, that is so far the only effective treatment. The main goals of clinicians and researchers are to make an early diagnosis, and to carry out molecular characterization to provide the patient with personalized treatment. Unfortunately, these goals are not easily achievable because of the heterogeneity of this tumor from anatomical, molecular, biological, and clinical perspectives. However, recent progress has been made in molecular characterization, surgical treatment, and management of intrahepatic cholangiocarcinoma and, this article deals with these advances.
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Affiliation(s)
- Maria Consiglia Bragazzi
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy.
| | - Rosanna Venere
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy
| | - Emanuela Ribichini
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Francesco Covotta
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Vincenzo Cardinale
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Domenico Alvaro
- Department Translational and Precision, Sapienza University of Rome, Italy
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Chiu TJ, Liu YW, Yong CC, Yin SM, Yeh CH, Chen YY. Combined Serum ALBUMIN with Neutrophil-to-Lymphocyte Ratio Predicts the Prognosis of Biliary Tract Cancer after Curative Resection. Cancers (Basel) 2023; 15:5474. [PMID: 38001734 PMCID: PMC10670262 DOI: 10.3390/cancers15225474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND The mainstay treatment of biliary tract cancer is complete tumor resection. Prior to surgery, risk stratification may help to predict and plan treatment approaches. In this study, we investigated the possibility of combining serum albumin concentrations and neutrophil-to-lymphocyte ratios (NLR) to create a score as ANS to predict the prognoses of biliary tract cancer before surgery. METHODS This study retrospectively collected serum albumin concentration, neutrophil, and lymphocyte data measured in biliary tract cancer patients slated to receive complete tumor resections within two weeks before surgery. From January 2013 to December 2019, 268 biliary tract cancer patients who had received tumor resections at our hospital were categorized into 3 ANS groups: ANS = 0 (high albumin and low NLR), ANS = 1 (low albumin or high NLR), and ANS = 2 (low albumin and high NLR). RESULTS Five-year survival rates were 70.1%, 47.6%, and 30.8% in the ANS = 0, 1, and 2 groups, respectively. The median overall survival time for the ANS = 0 group could not be determined by the end of the study, while those for ANS = 1 and ANS = 2 groups were 54.90 months and 16.62 months, respectively. The results of our multivariate analysis revealed that ANS could be used as an independent predictor of overall and recurrent-free survival. A high ANS was also correlated with other poor prognostic factors. CONCLUSIONS The ANS devised for this study can be used to predict postoperative survival in patients with BTC and to guide treatment strategies.
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Affiliation(s)
- Tai-Jan Chiu
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
| | - Yueh-Wei Liu
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chee-Chien Yong
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Shih-Min Yin
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Cheng-His Yeh
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; (Y.-W.L.); (C.-C.Y.); (S.-M.Y.); (C.-H.Y.)
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Alaimo L, Moazzam Z, Endo Y, Lima HA, Butey SP, Ruzzenente A, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Kitago M, Kim A, Ejaz A, Beane J, Cloyd J, Pawlik TM. The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2023; 30:4292-4301. [PMID: 36952150 DOI: 10.1245/s10434-023-13349-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/29/2023] [Indexed: 03/24/2023]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is associated with poor long-term outcomes, and limited evidence exists on optimal resection margin width. This study used artificial intelligence to investigate long-term outcomes and optimal margin width in hepatectomy for ICC. METHODS The study enrolled patients who underwent curative-intent resection for ICC between 1990 and 2020. The optimal survival tree (OST) was used to investigate overall (OS) and recurrence-free survival (RFS). An optimal policy tree (OPT) assigned treatment recommendations based on random forest (RF) counterfactual survival probabilities associated with each possible margin width between 0 and 20 mm. RESULTS Among 600 patients, the median resection margin was 4 mm (interquartile range [IQR], 2-10). Overall, 379 (63.2 %) patients experienced recurrence with a 5-year RFS of 28.3 % and a 5-year OS of 38.7 %. The OST identified five subgroups of patients with different OS rates based on tumor size, a carbohydrate antigen 19-9 [CA19-9] level higher than 200 U/mL, nodal status, margin width, and age (area under the curve [AUC]: training, 0.81; testing, 0.69). The patients with tumors smaller than 4.8 cm and a margin width of 2.5 mm or greater had a relative increase in 5-year OS of 37 % compared with the entire cohort. The OST for RFS estimated a 46 % improvement in the 5-year RFS for the patients younger than 60 years who had small (<4.8 cm) well- or moderately differentiated tumors without microvascular invasion. The OPT suggested five optimal margin widths to maximize the 5-year OS for the subgroups of patients based on age, tumor size, extent of hepatectomy, and CA19-9 levels. CONCLUSIONS Artificial intelligence OST identified subgroups within ICC relative to long-term outcomes. Although tumor biology dictated prognosis, the OPT suggested that different margin widths based on patient and disease characteristics may optimize ICC long-term survival.
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Affiliation(s)
- Laura Alaimo
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Zorays Moazzam
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Yutaka Endo
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Henrique A Lima
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Swatika P Butey
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | | | | | | | - Matthew Weiss
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, VA, USA
| | | | | | | | - Hugo P Marques
- Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal
| | | | - Carlo Pulitano
- Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia
| | - Feng Shen
- Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - François Cauchy
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - Alex Kim
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Aslam Ejaz
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Joal Beane
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Jordan Cloyd
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Wexner Medical Center, James Comprehensive Cancer Center, Department of Surgery, The Ohio State University, 395 West 12th Avenue, Suite 670, Columbus, OH, USA.
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Alaimo L, Moazzam Z, Pawlik TM. ASO Author Reflections: Long-Term Outcomes and Optimal Margin Width Among Patients Undergoing Hepatectomy for Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2023; 30:4302-4303. [PMID: 36964330 DOI: 10.1245/s10434-023-13351-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 02/15/2023] [Indexed: 03/26/2023]
Affiliation(s)
- Laura Alaimo
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Zorays Moazzam
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
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Jiang JH, Fang DZ, Hu YT. Influence of surgical margin width on survival rate after resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. BMJ Open 2023; 13:e067222. [PMID: 37156579 PMCID: PMC10174020 DOI: 10.1136/bmjopen-2022-067222] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/10/2023] Open
Abstract
OBJECTIVES Hepatectomy is the best treatment for patients with intrahepatic cholangiocarcinoma (ICC) at present, but there has been controversy about the width of surgical margins. In this study, we systematically investigated the effects of different surgical margin widths on the prognosis of patients with ICC undergoing hepatectomy. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed, Embase and Web of Science databases were systematically searched from inception to June 2022. ELIGIBILITY CRITERIA Cohort studies reported in English with patients who underwent negative marginal (R0) resection were included. The effects of surgical margin width on overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) in patients with ICC were assessed. DATA EXTRACTION AND SYNTHESIS Two investigators independently conducted literature screening and data extraction. Risk of bias was assessed using funnel plots and quality was assessed by the Newcastle-Ottawa Scale. Forest plots of HRs and their 95% CIs for outcome indicators were plotted. Heterogeneity was assessed and determined quantitatively using I2, and the stability of the study results was evaluated using sensitivity analysis. Analyses were performed using Stata software. RESULTS Nine studies were included. With the wide margin group (≥10 mm) as the control, pooled HR of OS in the narrow margin group (<10 mm) was 1.54 (95% CI 1.34 to 1.77). HRs of OS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.88 (1.45 to 2.42), 1.33 (1.03 to 1.72) and 1.49 (1.20 to 1.84), respectively. Pooled HR of DFS in the narrow margin group (<10 mm) was 1.51 (1.14 to 2.00). Pooled HR of RFS in the narrow margin group (<10 mm) was 1.35 (1.19 to 1.54). HRs of RFS in three subgroups where the margin was less than 5 mm ranged from 5 mm to 9 mm, or was less than 10 mm in length were 1.38 (1.07 to 1.78), 1.39 (1.11 to 1.74) and 1.30 (1.06 to 1.60), respectively. Neither lymph node lesions (HR 1.44, 95% CI 1.22 to 1.70) nor lymph node invasion (2.14, 1.39 to 3.28) was favourable for postoperative OS in patients with ICC. Lymph node metastasis (1.31, 1.09 to 1.57) was unfavourable for RFS in patients with ICC. CONCLUSION Patients with ICC who underwent curative hepatectomy with a negative margin ≥10 mm may have a long-term survival advantage, but lymph node dissection also needs to be considered. In addition, tumour-related pathological features need to be explored to see if they affect the surgical outcome of R0 margins.
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Affiliation(s)
- Jing-Hua Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Da-Zhang Fang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Yi-Ting Hu
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Zhejiang Shuren University, Shulan International Medical College, Hangzhou, China
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Dai YS, Hu HJ, Lv TR, Hu YF, Zou RQ, Li FY. The influence of resection margin width in patients with intrahepatic cholangiocarcinoma: a meta-analysis. World J Surg Oncol 2023; 21:16. [PMID: 36658564 PMCID: PMC9854153 DOI: 10.1186/s12957-023-02901-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 01/10/2023] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Some studies have pointed out that a wide resection margin can improve the prognosis of intrahepatic cholangiocarcinoma, but some researchers disagree and believe that a wide margin may increase complications. The optimal margin length of intrahepatic cholangiocarcinoma is controversial. METHOD The literature was searched in PubMed, MedLine, Embase, the Cochrane Library, and Web of Science until December 31, 2021, to evaluate the postoperative outcomes of patients with different margin width after resection. Odds ratios (ORs) with 95% confidence intervals were used to determine the effect size. RESULT A total of 11 articles were included in this meta-analysis, including 3007 patients. The narrow group had significantly lower 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates than the wide group. Postoperative morbidity and prognostic factors were also evaluated. CONCLUSION A resection margin width of over 10 mm is recommended in intrahepatic cholangiocarcinoma patients, especially in patients with negative lymph node and early tumor stage. When the resection margin width cannot be greater than 10 mm, we should ensure that the resection margin width is greater than 5 mm.
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Affiliation(s)
- Yu-Shi Dai
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
| | - Hai-Jie Hu
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
| | - Tian-run Lv
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
| | - Ya-Fei Hu
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
| | - Rui-Qi Zou
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
| | - Fu-Yu Li
- grid.412901.f0000 0004 1770 1022Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041 Sichuan Province China
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Song Y, Cai M, Li Y, Liu S. The focus clinical research in intrahepatic cholangiocarcinoma. Eur J Med Res 2022; 27:116. [PMID: 35820926 PMCID: PMC9277934 DOI: 10.1186/s40001-022-00741-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/26/2022] [Indexed: 12/11/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC), highly invasive and highly heterogeneous, has a poor prognosis. It has been confirmed that many risk factors are associated with ICC including intrahepatic lithiasis, primary sclerosing cholangitis (PSC), congenital abnormalities of the bile ducts, parasite infection, toxic exposures chronic liver disease (viral infection and cirrhosis) and metabolic abnormalities. In recent years, significant progress has been made in the clinical diagnosis and treatment of ICC. Advances in functional and molecular imaging techniques offer the possibility for more accurate preoperative assessment and detection of recurrence. Moreover, the combination of molecular typing and traditional clinical pathological typing provides accurate guarantee for clinical decision-making. Surgical resection is still the only radical treatment for ICC, while R0 resection, lymph node dissection, postoperative adjuvant therapy and recurrence resectomy have been confirmed to be beneficial for patients. New therapies including local therapy, molecular targeted therapy and immunotherapy are developing rapidly, which brings hopeful future for advanced ICC. The combination of traditional therapy and new therapy is the future development direction.
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Affiliation(s)
- Yinghui Song
- Department of Nuclear Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China
| | - Mengting Cai
- Department of Nuclear Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China
| | - Yuhang Li
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University Changsha, Changsha, 410005, Hunan, People's Republic of China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University Changsha, Changsha, 410005, Hunan, People's Republic of China. .,Central Laboratory of The First, Affiliated Hospital of Hunan Normal University, Changsha, 410015, China.
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Procopio F, Branciforte B, Nappo G, Di Tommaso L, Lleo A, Torzilli G. Meta-analysis on prognostic value of KRAS mutation in resected mass-forming cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1455-1463. [PMID: 35317947 DOI: 10.1016/j.ejso.2022.03.005] [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: 09/20/2021] [Revised: 02/14/2022] [Accepted: 03/08/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Despite survival improvements for other cancers, the prognosis of resected mass-forming cholangiocellular carcinoma (MFCCC) remains dismal. As a possible background of that, biologic factors could play some role. KRAS mutation has been investigated in the present systematic review and meta-analysis. METHODS MEDLINE, Embase and Cochrane Library databases were searched for studies reporting overall survival (OS) following liver resection for MFCCC with known KRAS status. Secondary outcomes included completeness of resection (R1 vs R0), pathological lymph node (LN) rate, tumor burden (multiple vs single), perineural invasion (PI) rate. RESULTS Eight studies comprising 604 patients resected for MFCCC were eligible for analysis. Of these, 23% of patients were mKRAS. The mKRAS MFCCC showed lower 1-year OS [odd ratio (OR) 3.45, 95% confidence interval (CIs) 1.85-6.42; p < 0.001], 3-years OS (OR 4.82, 95% CI 2.63-8.84; p < 0.001), and 5-years OS (OR 10.60, 95% CI 3.12-36.03; p < 0.001) compared to wtKRAS. Pooled-R1 resection rate was 18% for mKRAS and 23% for those with wtKRAS (OR 1.71, 95%CIs 0.70-4.19; p = 0.239). The pooled-pathological LNs rate was 23% in mKRAS vs 17% (OR 2.36, 95%CIs 0.75-7.48; p = 0.144). The pooled-multifocality rate was 55% in mKRAS vs 19% (OR 5.38, 95%CIs 1.76-16.48; p = 0.003), while the pooled-PI was 77% vs 31% (OR 6.59, 95%CIs 2.13-20.37; p = 0.001). CONCLUSION The KRAS mutation is relatively frequent in MFCCC. The mKRAS is strongly associated with a shortened survival and higher tumoral aggressiveness. Testing for KRAS mutations could be a valuable adjunct in opening a scenario to new treatments and improving prognosis of patients with MFCCC.
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Affiliation(s)
- Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy
| | - Bruno Branciforte
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Gennaro Nappo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Pancreatic Surgery Unit, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Division of Pathology, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy.
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Nguyen MLT, Toan NL, Bozko M, Bui KC, Bozko P. Cholangiocarcinoma Therapeutics: An Update. Curr Cancer Drug Targets 2021; 21:457-475. [PMID: 33563168 DOI: 10.2174/1568009621666210204152028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/12/2020] [Accepted: 11/20/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. OBJECTIVE This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. METHODS Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. RESULTS CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. CONCLUSION This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.
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Affiliation(s)
- Mai Ly Thi Nguyen
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Maria Bozko
- Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
| | - Khac Cuong Bui
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Przemyslaw Bozko
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
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Wada Y, Shimada M, Yamamura K, Toshima T, Banwait JK, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma. Hepatology 2021; 74:1371-1383. [PMID: 33725402 PMCID: PMC8443691 DOI: 10.1002/hep.31803] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/06/2021] [Accepted: 02/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.
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Affiliation(s)
- Yuma Wada
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Surgery, Tokushima University, Tokushima, Japan
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Kensuke Yamamura
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jasjit K Banwait
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
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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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Lu WF, Chen PQ, Yan K, Wu YC, Liang L, Yuan JY, Fu Y, Zhang HB. Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2021; 15:575-582. [PMID: 33899638 DOI: 10.1080/17474124.2021.1913053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. METHODS A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed. RESULTS The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RM & MVI (-), 58.0%, 36.1%, and 26.5% in narrow RM & MVI (-), 51.0%, 27.0%, and 24.3% in wide RM & MVI (+), and 39.0%, 20.4% and 14.3% in narrow RM & MVI (+) (p < 0.001). Multivariate analysis showed that RM & MVI were independent risk factors for the OS and RFS. CONCLUSION Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.
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Affiliation(s)
- Wen-Feng Lu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Pei-Qin Chen
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Kai Yan
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Ye-Chen Wu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Jian-Yong Yuan
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Yong Fu
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Hai-Bin Zhang
- Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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Park YH, Seo SH, An MS, Baik H, Lee CH. Prognostic Impact of Resection Margin Length in Patients Undergoing Resection for Mid-Common Bile Duct Cancer: A Single-Center Experience. Dig Surg 2021; 38:212-221. [PMID: 33784683 DOI: 10.1159/000513563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 12/01/2020] [Indexed: 12/10/2022]
Abstract
INTRODUCTION The purpose of this study was to analyze survival outcomes after segmental bile duct resection (BDR) for mid-common bile duct cancer according to the length of the tumor-free BDR margins. METHOD A total of 133 consecutive patients underwent BDR for mid-bile duct cancers between December 2007 and June 2017. The Cox proportional hazard model was used to verify the cutoff value of the R0 resection margin. The patients were divided into 3 groups according to resection margin status (group 1; R0 resection margin ≥5 mm; group 2, R0 resection margin <5 mm; and group 3, R1 resection margin). RESULTS The median follow-up period of the study cohort was 24 months. A resection margin of 5 mm in length was verified to be suitable as a reliable cutoff value. The median disease-free and overall survival (OS) periods were 32 and 49 months in group 1, 13 and 20 months in group 2, and 23 and 30 months in group 3, respectively (p = 0.03 and p < 0.001). The length of the tumor-free resection margin (hazard ratio, 2.01; 95% confidence interval, 1.10-3.67; p = 0.022) was independent factor affecting OS. CONCLUSIONS BDR for mid-bile duct cancer appears to be a feasible surgical option in selected patients with careful preoperative imaging assessment and intraoperative frozen-section diagnosis. Our results suggest achieving a BDR margin ≥5 mm to improve survival outcomes.
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Affiliation(s)
- Yo-Han Park
- Department of Surgery, College of Medicine Inje University, Busan Paik Hospital, Busan, Republic of Korea
| | - Sang Hyuk Seo
- Department of Surgery, College of Medicine Inje University, Busan Paik Hospital, Busan, Republic of Korea
| | - Min Sung An
- Department of Surgery, College of Medicine Inje University, Busan Paik Hospital, Busan, Republic of Korea
| | - HyungJoo Baik
- Department of Surgery, College of Medicine Inje University, Busan Paik Hospital, Busan, Republic of Korea
| | - Chan Ho Lee
- Department of Urology, College of Medicine Inje University, Busan Paik Hospital, Busan, Republic of Korea
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Italian Clinical Practice Guidelines on Cholangiocarcinoma - Part II: Treatment. Dig Liver Dis 2020; 52:1430-1442. [PMID: 32952071 DOI: 10.1016/j.dld.2020.08.030] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 08/17/2020] [Accepted: 08/17/2020] [Indexed: 01/27/2023]
Abstract
Currently, the only curative treatment for cholangiocarcinoma (CCA) is surgical resection, though this treatment is possible in less than 40% of patients. However, recent improvements in preoperative management have led to a higher number of patients who are candidates for this procedure. For unresectable patients, progress is ongoing in terms of locoregional and chemoradiation treatments and target therapies, especially in the definition of patient selection criteria. This is the second part of the Italian CCA guidelines, dealing with CCA treatment, that have been formulated in accordance with Italian National Institute of Health indications and developed according to the GRADE method and related advancements.
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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: 50] [Impact Index Per Article: 10.0] [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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Bartsch F, Baumgart J, Hoppe-Lotichius M, Straub BK, Heinrich S, Lang H. Intrahepatic cholangiocarcinoma - influence of resection margin and tumor distance to the liver capsule on survival. BMC Surg 2020; 20:61. [PMID: 32252724 PMCID: PMC7137203 DOI: 10.1186/s12893-020-00718-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 03/17/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is often diagnosed in advanced stage. Aim of this study was to analyse the influence of resection margins and tumor distance to the liver capsule on survival and recurrence in a single center with a high number of extended resections. METHODS From January 2008 to June 2018 data of all patients with ICC were collected and further analysed with Kaplan Meier Model, Cox regression or Chi2 test for categorical data. RESULTS Out of 210 included patients 150 underwent curative intended resection (71.4%). Most patients required extended resections (n = 77; 51.3%). R0-resection was achieved in 131 patients (87.3%) with minimal distances to the resection margin > 1 cm in 22, 0.5-1 cm in 11, 0.1-0.5 cm in 49 patients, and < 0.1 cm in 49 patients. Overall survival (OS) for margins > 0.5 cm compared to 0.5-0.1 cm or R1 was better, but without reaching significance. All three groups had significantly better OS compared to the irresectable group. Recurrence-free survival (RFS) was also better in patients with a margin > 0.5 cm than in the < 0.5-0.1 cm or the R1-group, but even without reaching significance. Different distance to the liver capsule significantly affected OS, but not RFS. CONCLUSIONS Wide resection margins (> 0.5 cm) should be targeted but did not show significantly better OS or RFS in a cohort with a high percentage of extended resections (> 50%). Wide margins, narrow margins and even R1 resections showed a significant benefit over the irresectable group. Therefore, extended resections should be performed, even if only narrow margins can be achieved.
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Affiliation(s)
- Fabian Bartsch
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Janine Baumgart
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Maria Hoppe-Lotichius
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Beate K Straub
- Department of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Stefan Heinrich
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
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Morales-Cruz M, Armillas-Canseco F, Carpinteyro-Espín P, Domínguez-Rosado I, Mercado M. Prognostic value of positive surgical margins after resection of cholangiocarcinoma. Experience at a high-volume hospital center specializing in hepatopancreatobiliary surgery. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2018.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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20
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Prognostic value of positive surgical margins after resection of cholangiocarcinoma. Experience at a high-volume hospital center specializing in hepatopancreatobiliary surgery. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2019; 85:18-24. [PMID: 31685297 DOI: 10.1016/j.rgmx.2018.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 11/15/2018] [Accepted: 11/26/2018] [Indexed: 11/22/2022]
Abstract
INTRODUCTION AND AIMS Cholangiocarcinoma accounts for 3% of gastrointestinal tumors and is the second most frequent hepatic neoplasia after hepatocellular carcinoma. The primary aim was to evaluate the median disease-free period and survival in patients with cholangiocarcinoma diagnosis through the comparison of R0 and R1 resection margins. MATERIAL AND METHODS A retrospective analysis was conducted on 36 patients that underwent some type of surgical resection due to cholangiocarcinoma diagnosis, within the time frame of 2000-2017, at a center specializing in hepatopancreatobiliary surgery. Population, preoperative, and oncologic variables were included. The IBM Statistical Package for the Social Sciences for Mac, version 16.0, software (IBM SPSS Inc., Chicago, IL, USA) was employed. RESULTS Thirty-one patients underwent hepatectomy, the Whipple procedure, or bypass surgery, depending on tumor location. The statistical significance of survival between patients with positive margins and those with negative margins was evaluated through the Mann-Whitney U test, with a P<.05 as the reference value. No statistically significant difference was found. The overall morbidity rate was 58.06% (n=18) and the mortality rate was 12.9% (n=4). CONCLUSIONS No statistically significant difference in relation to the incidence of disease recurrence or general survival resulted from the comparison of microscopically positive surgical margins (R1) and negative surgical margins (R0). There was also no correlation between preoperative CA 19-9 levels and disease prognosis.
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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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Guowei H, Yuan L, Ma L, Zhongyang L, Zhixing S, Lin L, Minqi L. The diagnostic efficacy of CYFRA21-1 on intrahepatic cholangiocarcinoma: A meta-analysis. Clin Res Hepatol Gastroenterol 2019; 43:266-272. [PMID: 30503663 DOI: 10.1016/j.clinre.2018.10.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 10/10/2018] [Accepted: 10/15/2018] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the reliability and accuracy of Cytokeratin-19-fragment (CYFRA21-1) in the diagnosis of intrahepatic cholangiocarcinoma (ICC) based on literature meta-analysis and the diagnostic efficacy and clinical application of CYFRA21-1 in ICC. METHODS MEDLINE, China National Knowledge Infrastructure Library and other databases were used to base the inclusion and exclusion criteria. In addition, relevant data from studies on CYFRA21-1 were used to diagnose ICC individually or in combination was retrieved for meta-analysis. Research papers were manually screened by two independent researchers. The selected papers were evaluated by QUADAS-2 standard. The SROC was plotted according to the extracted data combined with the results of diagnosis to evaluate the diagnostic efficiency of CYFRA21-1 in ICC. RESULTS Six articles with an overall sample size of 731 cases, including 217 cases in the positive group and 514 cases in the control group, met the inclusion criteria and were included for the systematic review. When CYFRA21-1 was used for ICC diagnosis, the pooled diagnostic indices were as follows: sensitivity 0.81 (95%CI: 0.75-0.86); specificity, 0.86 (95%CI: 0.82-0.89); positive likelihood rate, 4.72 (95%CI: 2.02-11.02); negative likelihood ratio, 0.25 (95%CI: 0.19-0.33); diagnostic odds ratio, 27.43 (95%CI: 13.20-57.00); and area under the ROC curve, 0.904 (SE = 0.0171). CONCLUSION CYFRA21-1 is of certain value in the diagnosis of intrahepatic cholangiocarcinoma.
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Affiliation(s)
- He Guowei
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Liao Yuan
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Li Ma
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Liu Zhongyang
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Song Zhixing
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Li Lin
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China
| | - Luo Minqi
- Department of clinical laboratory, Third affiliated hospital of Sun Yat-sen University, No. 600, Tianhe road, Guangzhou, Guangdong, PR China.
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Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. Eur J Surg Oncol 2019; 45:1432-1438. [PMID: 30914290 DOI: 10.1016/j.ejso.2019.03.023] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/01/2019] [Accepted: 03/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Chemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear. PATIENTS AND METHODS Using the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model. RESULTS Of the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64-0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group. CONCLUSION In this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.
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Affiliation(s)
| | - Hao Xie
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Irbaz Bin-Riaz
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Prabin Sharma
- Department of Gastroenterology, Yale New Haven Health - Bridgeport Hospital, Bridgeport, CT, 06610, USA
| | - Urshila Durani
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Gaurav Goyal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Bijan Borah
- Robert D. and Patricia E. Kern Mayo Clinic Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Mitesh J Borad
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA
| | | | - Amit Mahipal
- Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
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Ma KW, Cheung TT, Leung B, She BWH, Chok KSH, Chan ACY, Dai WC, Lo CM. Adjuvant chemotherapy improves oncological outcomes of resectable intrahepatic cholangiocarcinoma: A meta-analysis. Medicine (Baltimore) 2019; 98:e14013. [PMID: 30702559 PMCID: PMC6380775 DOI: 10.1097/md.0000000000014013] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 11/26/2018] [Accepted: 12/13/2018] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE To define the role of adjuvant chemotherapy in the management of resectable intrahepatic cholangiocarcinoma (ICC) by performing a meta-analysis. SUMMARY BACKGROUND DATA Oncological benefit of adjuvant chemotherapy in resectable ICC remains controversial, high-level evidence in such context is lacking. METHOD A comprehensive search using Pubmed, EMbase, and Web of Science was performed from inception to October 2018. Studies compared the survival of patients receiving adjuvant chemotherapy versus surgery alone were included. Data were analyzed using random effect model. Quality of each study and presence of publication bias were assessed by Newcastle-Ottawa score (NOS) and funnel plot with Egger test respectively. RESULTS The present meta-analysis included 15 studies (all were retrospective series) and 5060 patients. Adjuvant chemotherapy was administered either intravenously or intra-arterially in the form of trans-arterial chemo-embolization (TACE). The average NOS for the included studies was 6.5. Pooled analysis of the included studies demonstrated significant advantage in the adjuvant chemotherapy group (HR 0.66, 0.55-079, P <.001, I-square [I] = 20.8%). After 2 studies were removed for heterogeneity, advantage of adjuvant chemotherapy remained (HR 0.72, 0.62-0.84, P <.001, I = 0%). Funnel plot suggested no significant publication bias (Egger test, 2-tailed P = .203). Subgroup analyses suggested that intravenous route of chemotherapy injection (P <.001) and use of gemcitabine base regimen (P = .004) are associated with improved overall survival. Adjuvant chemotherapy did not improve disease-free survival in subgroup analysis (P = .94). CONCLUSION Adjuvant chemotherapy is associated with improved overall survival and should be considered in patients with ICC following curative resection and in particular to patients with advance disease.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital
| | | | | | | | | | | | | | - Chung Mau Lo
- Department of Surgery, Queen Mary Hospital
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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Ma KW, Cheung TT, She WH, Chok KSH, Chan ACY, Dai WC, Tsang SHY, Lo CM. Major postoperative complications compromise oncological outcomes of patients with intrahepatic cholangiocarcinoma after curative resection - A 13-year cohort in a tertiary center. Asian J Surg 2019; 42:164-171. [PMID: 29472064 DOI: 10.1016/j.asjsur.2018.01.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 01/16/2018] [Accepted: 01/23/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/OBJECTIVE Hepatectomy is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative complication and oncological outcome has not been defined. We aimed to elucidate the effect of postoperative complication on long-term survival of ICC patients after curative resection. METHODS Data of consecutive patients who had curative resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor were excluded. Clinicopathological data and postoperative events were extracted from database for survival analysis. RESULTS There were 107 patients in our series. Their median age was 61 years. The median follow-up time was 24 months. The median tumor size was 6 cm. Major hepatectomy was required in 52.3% of them. The median operation time and blood loss was 439 minutes and 0.9L respectively. R0 resection was achieved in 88.8% of them. The median length of stay was 11 days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major complications were found in 20.6% of them. Patients with postoperative complications had significantly inferior survival than patients without (3-yr DFS 38% vs. 27%, P = 0.001; 3-yr overall: 51% vs. 27%, P < 0.001). Multivariable analysis showed that postoperative complication was an independent factor associated with disease-free survival (OR 1.9 95% C.I. 1.10-3.24, P = 0.021) and overall survival (OR 2.1, 95% C.I. 1.13-3.93, P = 0.018). CONCLUSION Postoperative complication has a significant impact on ICC patients' long-term survival. Extra measures such as adjuvant chemotherapy should be considered for patients who develop major complications after surgery.
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Affiliation(s)
- Ka Wing Ma
- 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.
| | - Wong Hoi She
- 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
| | - Albert Chi Yan Chan
- Department of Surgery, 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
| | - Simon Hin Yin Tsang
- Department of Surgery, 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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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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Chen Y, Hong Z, Lu S, Zhang N, Rong G, Chang X, Liu Z, Bai W, Dong Z, Gao X, Zeng Z, Lu Y. Downregulated Expression of Tropomyosin 1 in Intrahepatic Cholangiocarcinoma: A Predictor of Recurrence and Prognosis. Med Sci Monit 2018; 24:7875-7882. [PMID: 30390420 PMCID: PMC6231322 DOI: 10.12659/msm.907340] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background The downregulation of tropomyosin 1 (TPM1) has been observed in various tumors, but few studies have focused on the clinical significance of TPM1 in intrahepatic cholangiocarcinoma (ICC). In the present study, we investigated the prognostic significance of TPM1 in ICC. Material/Methods A total of 124 patients with ICC were enrolled in this study. Quantitative real-time polymerase chain reaction (qRT-RCR) was performed to examine the mRNA levels of TPM1 in ICC tissue samples and adjacent noncancerous tissue specimens, while the protein level of TPM1 in tissue specimens were investigated using immunohistochemistry assay. The correlation of TPM1 with clinicopathological features of ICC was analyzed by chi-square test. Survival analysis was performed with Kaplan-Meier method. The Cox proportional hazards model was used to evaluate the prognostic value of TPM1 in patients with ICC. Results TPM1 expression was significantly downregulated in ICC tissues at mRNA and protein levels (P<0.001 for both). Downregulated TPM1 mRNA was negatively associated with tumor size (P=0.001) and TNM stage (P=0.007). Moreover, survival analysis demonstrated that patients with low TPM1 expression had a shorter overall survival (OS) (P<0.001) and recurrence-free survival (RFS) (P<0.001) than those with high TPM1 expression. Additionally, multivariate analysis showed that TPM1 could be a potential biomarker for predicting the recurrence (HR=4.632, 95% CI: 3.832–10.368, P<0.001) and survival outcome (HR=5.320, 95% CI: 2.627–11.776, P<0.001) of ICC. Conclusions TPM1 may serve as a useful biomarker for predicting tumor recurrence and prognosis in patients with ICC.
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Affiliation(s)
- Yan Chen
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Zhixian Hong
- Department of Hepatobiliary Surgery, Beijing 302 Hospital, Beijing, China (mainland)
| | - Shanshan Lu
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Ning Zhang
- Department of Integrated Traditional Chinese Medicine (TCM) and Western Medicine, Beijing 302 Hospital, Beijing, China (mainland)
| | - Guanghua Rong
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Xiujuan Chang
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Ze Liu
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Wenlin Bai
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Zheng Dong
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Xudong Gao
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Zhen Zeng
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
| | - Yinying Lu
- Comprehensive Liver Cancer Center, Beijing 302 Hospital, Beijing, China (mainland)
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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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Liu S, Jiang B, Li H, He Z, Lv P, Peng C, Wang Y, Cheng W, Xu Z, Chen W, Liu Z, Zhang B, Shen S, Xiang S. Wip1 is associated with tumorigenity and metastasis through MMP-2 in human intrahepatic cholangiocarcinoma. Oncotarget 2017; 8:56672-56683. [PMID: 28915621 PMCID: PMC5593592 DOI: 10.18632/oncotarget.18074] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 04/26/2017] [Indexed: 12/21/2022] Open
Abstract
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC.
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Affiliation(s)
- Sulai Liu
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Bo Jiang
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Hao Li
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Zili He
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Pin Lv
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Chuang Peng
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Yonggang Wang
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Wei Cheng
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Zhengquan Xu
- Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China
| | - Wei Chen
- Department of Thoracic, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People's Republic of China
| | - Zhengkai Liu
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Bao Zhang
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Shengqian Shen
- Department of Hepatobiliary Surgery/Hunan Research Center of Biliary Disease, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China
| | - Shuanglin Xiang
- Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan Province, People's Republic of China
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30
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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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31
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Wang H, Liu W, Tian M, Tang Z, Jiang X, Zhou P, Ding Z, Peng Y, Dai Z, Qiu S, Zhou J, Fan J, Shi Y. Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection. Biosci Trends 2017; 11:469-474. [DOI: 10.5582/bst.2017.01080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Han Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Weiren Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Mengxin Tian
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Zheng Tang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Xifei Jiang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Peiyun Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Zhenbin Ding
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Yuanfei Peng
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Zhi Dai
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Shuangjian Qiu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
- Institutes of Biomedical Sciences, Fudan University
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
- Institutes of Biomedical Sciences, Fudan University
| | - Yinghong Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education
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