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Mattiolo P, De Bellis M, Mafficini A, Fassan M, Bevere M, Ciulla C, Bersani S, Lawlor RT, Milella M, Scarpa A, Luchini C, Ruzzenente A. Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature. J Gastrointest Cancer 2024; 55:1634-1646. [PMID: 39283582 PMCID: PMC11464565 DOI: 10.1007/s12029-024-01113-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma. CASE PRESENTATION A 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations. CONCLUSIONS This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement.
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Affiliation(s)
- Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona, Italy.
| | - Mario De Bellis
- Division of General and Hepato-Biliary Surgery, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University and Hospital Trust of Verona, Verona, Italy
| | - Andrea Mafficini
- Department of Engineering for Innovation Medicine (DIMI), University of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
| | - Michele Bevere
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Calogero Ciulla
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona, Italy
| | - Samantha Bersani
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona, Italy
| | - Rita T Lawlor
- Department of Engineering for Innovation Medicine (DIMI), University of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Michele Milella
- Department of Engineering for Innovation Medicine (DIMI), University of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, University and Hospital Trust of Verona, Verona, Italy.
- ARC-Net Research Center, University of Verona, Verona, Italy.
| | - Andrea Ruzzenente
- Division of General and Hepato-Biliary Surgery, Department of Surgery, Dentistry, Gynecology, and Pediatrics, University of Verona, University and Hospital Trust of Verona, Verona, Italy
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Chamadol N, Laopaiboon V, Jareanrat A, Thanasukarn V, Srisuk T, Luvira V, Sarkhampee P, Ungpinitpong W, Khamvijite P, Chumnanua Y, Nethuwakul N, Sodarat P, Thammarit S, Techasen A, Thuanman J, Tawarungruang C, Thinkhamrop B, Sa-Ngiamwibool P, Loilome W, Prajumwongs P, Titapun A. Improvement of survival outcomes of cholangiocarcinoma by ultrasonography surveillance: Multicenter retrospective cohorts. Heliyon 2024; 10:e38191. [PMID: 39381227 PMCID: PMC11458967 DOI: 10.1016/j.heliyon.2024.e38191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 09/16/2024] [Accepted: 09/19/2024] [Indexed: 10/10/2024] Open
Abstract
Background Most cholangiocarcinoma (CCA) patients present with late stage of disease because of the difficulty to diagnosis at an early stage, resulting in poor survival of CCA patients. The Cholangiocarcinoma Screening and Care Program showed that ultrasound screening was an effective tool for detecting early stage CCA. This study aims to evaluate the survival outcome of patients diagnosed by ultrasound screening (US) compared to walk-in symptomatic patients. Methods The retrospective clinical data and medical records for this study were accessed in June 30, 2021. 5-year survival rates (5-YSR) and median survival time (MST) of CCA were calculated using the Kaplan-Meier method. Multivariate analyses were performed for significant factors from univariate analyses. Results A total of 711 histologically proven CCA cases were examined including ultrasound screening and walk-in groups. The screening group having 5-YSR was 53.9 %, and MST was of 67.2 months, while walk-in group, the 5-YSR was 21.9 % and MST was 15.6 months (p < 0.001). In addition, multivariate analyses revealed that screening program was an independent factor to predict a good outcome of CCA patients when compared with walk-in group (p = 0.014). Conclusion US is an effective tool for detecting early stage CCA leading to improve clinical outcome of CCA patients. Practically, US should be considered as a first tool for screening CCA in risk populations.
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Affiliation(s)
- Nittaya Chamadol
- Departments of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Vallop Laopaiboon
- Departments of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Apiwat Jareanrat
- Departments of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Vasin Thanasukarn
- Departments of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Tharatip Srisuk
- Departments of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Vor Luvira
- Departments of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Poowanai Sarkhampee
- Departments of Surgery, Sunpasitthiprasong Hospital, Ubon Ratchathani Province, Thailand
| | | | | | | | | | | | - Samrit Thammarit
- Departments of Surgery, Udonthani Hospital, Udon Thani Province, Thailand
| | - Anchalee Techasen
- Departments of Clinical Microbiology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Jaruwan Thuanman
- Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Khon Kean, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Chaiwat Tawarungruang
- Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Khon Kean, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Bandit Thinkhamrop
- Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Khon Kean, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Prakasit Sa-Ngiamwibool
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Watcharin Loilome
- Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Piya Prajumwongs
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
| | - Attapol Titapun
- Departments of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
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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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Harada K, Fujikawa T, Uemoto Y, Matsuoka T. Long-Term Oncological Control by Repeated Minimally Invasive Hepatectomy for Intrahepatic Cholangiocarcinoma Exhibiting Atypical Marker Expression of CK7-CK20+: A Case Report. Cureus 2023; 15:e50639. [PMID: 38229809 PMCID: PMC10789588 DOI: 10.7759/cureus.50639] [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] [Accepted: 12/16/2023] [Indexed: 01/18/2024] Open
Abstract
There are few reports of repeated liver resections being performed multiple times for intrahepatic recurrence of intrahepatic cholangiocarcinoma (ICC). We performed five minimally invasive liver resections and two minimally invasive lung resections for ICC with metachronous intrahepatic recurrence and lung metastases. Pathological examination revealed that all resected tumors were moderately differentiated mass-forming ICC with immunohistochemical marker expression of CK7 negative and CK20 positive. We present this as a rare case of ICC with atypical marker expression in which long-term tumor control was achieved with multiple minimally invasive liver resections over 47 months from the initial diagnosis.
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Affiliation(s)
- Kei Harada
- Surgery, Kokura Memorial Hospital, Kitakyushu, JPN
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Miyazu T, Ishida N, Asai Y, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Osawa S, Baba S, Sugimoto K. Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports. World J Gastrointest Surg 2023; 15:1224-1231. [PMID: 37405109 PMCID: PMC10315124 DOI: 10.4240/wjgs.v15.i6.1224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 03/10/2023] [Accepted: 04/12/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.
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Affiliation(s)
- Takahiro Miyazu
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Natsuki Ishida
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yusuke Asai
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Tamura
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Baba
- Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
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Koonmee S, Sa-Ngiamwibool P, Aphivatanasiri C, Kunprom W, Intarawichian P, Bamrungkit W, Sangkhamanon S, Thanee M. Pathology of Cholangiocarcinoma. Recent Results Cancer Res 2023; 219:91-107. [PMID: 37660332 DOI: 10.1007/978-3-031-35166-2_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
The liver excretes bile through the biliary system, which has a complicated anatomical structure. Cholangiocarcinoma, a malignant bile duct epithelial tumor, is separated into intrahepatic and extrahepatic portions depending on the structure of the bile duct and exhibits both similarities and varieties in patient presentations and staging. The three main macroscopic characteristics of cholangiocarcinoma-mass formating, intraductal growth, and periductal infiltrating types-allow pathologists and surgeons to see and analyze the cancerous tissue. The majority of cholangiocarcinoma patients are in advanced stages and poor prognosis. Although surgery is the main treatment option, target therapy based on molecular pathology background offers hope for improving patient's prognosis.
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Affiliation(s)
- Supinda Koonmee
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
| | - Prakasit Sa-Ngiamwibool
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Chaiwat Aphivatanasiri
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Waritta Kunprom
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | | | - Walailak Bamrungkit
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Sakkarn Sangkhamanon
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Malinee Thanee
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
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Smith EN, Coleman A, J. Galgano S, Burgan CM, Porter KK. Cholangiocarcinoma. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:133-159. [DOI: 10.1016/b978-0-323-69538-1.00011-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sa-Ngiamwibool P, Aphivatanasiri C, Sangkhamanon S, Intarawichian P, Kunprom W, Thanee M, Prajumwongs P, Loilome W, Khuntikeo N, Titapun A, Jareanrat A, Thanasukarn V, Srisuk T, Luvira V, Eurboonyanun K, Promsorn J, Wee A, Koonmee S. Modification of the AJCC/UICC 8th edition staging system for intrahepatic cholangiocarcinoma: proposal for an alternative staging system from cholangiocarcinoma-prevalent Northeast Thailand. HPB (Oxford) 2022; 24:1944-1956. [PMID: 35810105 DOI: 10.1016/j.hpb.2022.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/18/2022] [Accepted: 06/13/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) arises from bile ducts within the liver. Thailand has the highest incidence of CCA worldwide, with a high mortality rate. Early diagnosis and accurate prognostic stratification can improve overall survival. We aim to modify the AJCC/UICC 8th edition staging system for iCCA by creating the Khon Kaen University (KKU) staging system for more precise patient stratification and prognostic prediction. METHODS A total of 298 iCCA patients who underwent hepatectomy were included in this retrospective study at the Srinagarind Hospital, Khon Kaen University, Thailand. Univariate and multivariate analysis were performed to examine survival rate, hazard ratio, and prognostic factors. RESULTS Univariate and multivariate analysis of the cohort showed that growth patterns, histological type, histological grade, lymph node metastasis and distant metastasis were independent prognostic factors when compared to the respective reference groups. The 8th AJCC staging system incorporated growth patterns into the KKU staging system. This model modified AJCC stages I, II, and III for better prediction of patient survival. CONCLUSION Growth patterns were incorporated to improve the 8th AJCC staging system for prognostication of iCCA patients in Northeast Thailand. We propose the KKU staging system as an alternative model for iCCA staging to augment the accuracy of survival prognostication.
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Affiliation(s)
- Prakasit Sa-Ngiamwibool
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chaiwat Aphivatanasiri
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sakkarn Sangkhamanon
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piyapharom Intarawichian
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Waritta Kunprom
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Malinee Thanee
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piya Prajumwongs
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Watcharin Loilome
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Narong Khuntikeo
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Attapol Titapun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Apiwat Jareanrat
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Vasin Thanasukarn
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Tharatip Srisuk
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Vor Luvira
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Kulyada Eurboonyanun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Julaluck Promsorn
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Aileen Wee
- Department of Pathology, National University Hospital, Singapore
| | - Supinda Koonmee
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
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9
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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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10
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Kingham TP, Aveson VG, Wei AC, Castellanos JA, Allen PJ, Nussbaum DP, Hu Y, D'Angelica MI. Surgical management of biliary malignancy. Curr Probl Surg 2021; 58:100854. [PMID: 33531120 PMCID: PMC8022290 DOI: 10.1016/j.cpsurg.2020.100854] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Affiliation(s)
| | - Victoria G Aveson
- New York Presbyterian Hospital-Weill Cornel Medical Center, New York, NY
| | - Alice C Wei
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Duke Cancer Center, Chief, Division of Surgical Oncology, Duke University School of Medicine, Durham, NC
| | | | - Yinin Hu
- Division of Surgical Oncology, University of Maryland, Baltimore, MD
| | - Michael I D'Angelica
- Memorial Sloan Kettering Cancer Center, Professor of Surgery, Weill Medical College of Cornell University, New York, NY..
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11
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Inchingolo R, Maino C, Gatti M, Tricarico E, Nardella M, Grazioli L, Sironi S, Ippolito D, Faletti R. Gadoxetic acid magnetic-enhanced resonance imaging in the diagnosis of cholangiocarcinoma. World J Gastroenterol 2020; 26:4261-4271. [PMID: 32848332 PMCID: PMC7422539 DOI: 10.3748/wjg.v26.i29.4261] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 06/16/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
The use of liver magnetic resonance imaging is increasing thanks to its multiparametric sequences that allow a better tissue characterization, and the use of hepatobiliary contrast agents. This review aims to evaluate gadoxetic acid enhanced magnetic resonance imaging in the diagnosis and staging of cholangiocarcinoma and its different clinical and radiological classifications proposed in the literature. We also analyze the epidemiology, risk factors in correlation with clinical findings and laboratory data.
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Affiliation(s)
- Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Cesare Maino
- Department of Diagnostic Radiology, School of Medicine, University of Milano-Bicocca, Monza 20900, Italy
| | - Marco Gatti
- Department of Surgical Sciences, Radiology Unit, University of Turin, Turin 10126, Italy
| | - Eleonora Tricarico
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Michele Nardella
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Luigi Grazioli
- Department of Radiology, Spedali Civili, University of Brescia, Brescia 25123, Italy
| | - Sandro Sironi
- Department of radiology, Papa Giovanni XXIII Hospital, University Milano-Bicocca, Bergamo 20110, Italy
| | - Davide Ippolito
- Department of Diagnostic Radiology, School of Medicine, University of Milano-Bicocca, Monza 20900, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, Radiology Unit, University of Turin, Turin 10126, Italy
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12
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Zhang Z, Zhou Y, Hu K, Wang D, Wang Z, Huang Y. Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study. BMC Cancer 2020; 20:270. [PMID: 32228636 PMCID: PMC7106692 DOI: 10.1186/s12885-020-06781-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 03/23/2020] [Indexed: 02/06/2023] Open
Abstract
Background In the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial. Methods ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated. Results There was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS and P = 0.8004 in OS). Conclusion PNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.
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Affiliation(s)
- Zeyu Zhang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yufan Zhou
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Kuan Hu
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Dong Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhiming Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yun Huang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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13
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Shimizu S, Okumura T, Oshiro Y, Fukumitsu N, Fukuda K, Ishige K, Hasegawa N, Numajiri H, Murofushi K, Ohnishi K, Mizumoto M, Nonaka T, Ishikawa H, Sakurai H. Clinical outcomes of previously untreated patients with unresectable intrahepatic cholangiocarcinoma following proton beam therapy. Radiat Oncol 2019; 14:241. [PMID: 31881895 PMCID: PMC6935160 DOI: 10.1186/s13014-019-1451-5] [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] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 12/19/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The effectiveness of proton beam therapy (PBT) as initial treatment for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is unclear, particularly as related to ICC histological subtypes. We performed this study to address this gap in knowledge. METHODS Thirty-seven patients with unresectable ICC who underwent PBT as their initial treatment were evaluated. Twenty-seven patients had Child-Pugh class A liver function, 11 exhibited jaundice, and 10 had multiple tumors. Nineteen, 7, and 11 tumors were classified as mass forming (MF), periductal infiltrating (PI), and intraductal growth (IG) types, respectively, based on gross appearance in imaging studies. Patients were classified into the curative group (n = 25) and palliative group (n = 12) depending on whether the planning target volume covered all the macroscopic tumors. RESULTS The 1- and 2-year overall survival rates were 60.3, and 41.4%, respectively; the median survival time (MST) was 15 months for all patients. The MSTs for curative and palliative groups were 25 and 7 months, respectively. Curative treatment and adjuvant chemotherapy significantly improved overall survival, while the presence of periductal infiltrating type tumors was a negative prognostic factor. In the curative group, the 1- and 2-year local control rates were 100 and 71.5%, respectively, while the 1-, and 2-year progression-free survival rates were 58.5, and 37.6%, respectively. No severe acute toxicities were observed. Three patients experienced grade 3 biliary tract infection, although it was unclear whether this was radiotherapy-related. CONCLUSION PBT may yield to improve survival and local tumor control among patients with unresectable ICC.
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Affiliation(s)
- Shosei Shimizu
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Toshiyuki Okumura
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshiko Oshiro
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Nobuyoshi Fukumitsu
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kuniaki Fukuda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kazunori Ishige
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Naoyuki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Haruko Numajiri
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Keiko Murofushi
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kayoko Ohnishi
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masashi Mizumoto
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tetsuo Nonaka
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hitoshi Ishikawa
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
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14
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Cheng R, Du Q, Ye J, Wang B, Chen Y. Prognostic value of site-specific metastases for patients with advanced intrahepatic cholangiocarcinoma: A SEER database analysis. Medicine (Baltimore) 2019; 98:e18191. [PMID: 31804337 PMCID: PMC6919521 DOI: 10.1097/md.0000000000018191] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and increasing incidence. Due to its asymptomatic manifestation, ICC often progresses to a metastatic stage on diagnosis. The current study attempted to evaluate the prognostic value of site-specific metastases in patients with metastatic ICC.Surveillance, Epidemiology, and End Results (SEER) database (2010-2015) was queried and metastatic ICC patients were classified according to the metastatic sites. Kaplan-Meier analysis was used for survival comparisons and multivariate analysis was performed to elicit characteristics independently associated with survival.A total of 1567 patients were identified and included in the analysis. Compared with those with multiple-site metastases, patients with single-site metastases had better prognostic outcomes. Among the single-site metastases, regional lymph nodes metastases had the best prognosis; liver metastases had better prognostic outcomes than bone metastases; no significant difference was found between lung and bone or liver metastasis. Local treatment of primary tumor might benefit patients with isolated lymph nodes metastases and few exceptional cases of patients with liver metastases.Different metastatic sites have distinct impact on the survival outcomes of patients with advanced ICC and highly selected subset of them might benefit from the local treatment of the primary tumor.
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15
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Ohira M, Kobayashi T, Hashimoto M, Tazawa H, Abe T, Oshita A, Kohashi T, Irei T, Oishi K, Ohdan H. Prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative resection: A retrospective cohort study. Int J Surg 2018; 54:156-162. [DOI: 10.1016/j.ijsu.2018.04.058] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Revised: 04/10/2018] [Accepted: 04/29/2018] [Indexed: 12/19/2022]
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16
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Burt AD, Alves V, Bedossa P, Clouston A, Guido M, Hübscher S, Kakar S, Ng I, Park YN, Reeves H, Wyatt J, Yeh MM, Ellis DW. Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2018; 73:369-385. [DOI: 10.1111/his.13520] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alastair D Burt
- Faculty of Health and Medical Sciences; University of Adelaide; Adelaide Australia
| | - Venâncio Alves
- Department of Pathology; University of São Paulo School of Medicine; São Paulo Brazil
| | - Pierre Bedossa
- Pathology Department; AP-HP; Beaujon Hospital; Clichy France
- Centre de Recherche Bichat-Beaujon; University Paris-Diderot; Paris France
| | - Andrew Clouston
- Envoi Specialist Pathologists; Brisbane Queensland Australia
| | - Maria Guido
- Surgical Pathology and Cytopathology Unit; Department of Medicine-DIMED; University of Padova; Padova Italy
| | - Stefan Hübscher
- Department of Cellular Pathology; Institute of Immunology and Immunotherapy; University of Birmingham; Queen Elizabeth Hospital; Birmingham UK
| | | | - Irene Ng
- Department of Pathology; State Key Laboratory for Liver Research; The University of Hong Kong; Hong Kong Hong Kong
| | - Young N Park
- Department of Pathology Yonsei; Univesity College of Medicine Seodaemun-gu; Seoul Korea
| | - Helen Reeves
- Northern Institute for Cancer Research, Newcastle University; Newcastle upon Tyne UK
| | - Judith Wyatt
- Department of Histopathology; St James University Hospital; Leeds UK
| | - Matthew M Yeh
- Department of Pathology; University of Washington School of Medicine; Seattle WA USA
| | - David W Ellis
- Clinpath Laboratories; Kent Town South Australia Australia
- ICCR Steering Group Representative; Adelaide Australia
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17
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Hu J, Chen FY, Zhou KQ, Zhou C, Cao Y, Sun HC, Fan J, Zhou J, Wang Z. Intrahepatic cholangiocarcinoma patients without indications of lymph node metastasis not benefit from lymph node dissection. Oncotarget 2017; 8:113817-113827. [PMID: 29371948 PMCID: PMC5768365 DOI: 10.18632/oncotarget.22852] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 11/13/2017] [Indexed: 12/21/2022] Open
Abstract
Background: To investigate the necessity of routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) patients without indications of lymph node metastasis (LNM) preoperatively. Methods: 422 consecutive ICC patients who undergone curative resection from January 2009 to December 2014 were enrolled and categorized as two groups (hepatectomy only or hepatectomy plus LND). Clinicopathologic data was compared between the groups by χ2 or Fisher’s exact test. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan–Meier method and differences were analyzed using the log-rank test. Cox regression model was adopted for multivariable analysis. Results: The median OS time of all 422 patients was 41.4 months. One-, 3-, and 5-year OS was 67%, 47%, and 35%, respectively. A total of 73 patients had undergone curative resection combined with LND, of whom 20.5% (15/73) were confirmed lymph node positive pathologically. The clinicopathologic characteristics between LND and control groups showed no significant differences. Of the 422 patients, 271 patients had recurrence. The recurrence rates were 65.8% for the LND group and 63.9% for the non-LND group. Survival analysis revealed that, neither the OS (LND vs. non-LND: 32.2 months vs. 46.2 months; p = 0.16) nor the RFS (LND vs. non-LND: 23.1 months vs. 17.0 months; p = 0.09) had significant difference. Multivariate analysis revealed that tumor size, tumor number, carbohydrate antigen19-9, carcinoembryonic antigen, and gamma-glutamyl transpeptidase were independent predictive factors for OS and RFS. Conclusion: Routine LND may not improve survival in resectable ICC patients with negative LNM diagnosis before operation.
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Affiliation(s)
- Jie Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Fei-Yu Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Kai-Qian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Cheng Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Ya Cao
- Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan, China
| | - Hui-Chuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China.,State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China.,State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, China
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18
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Si A, Li J, Xing X, Lei Z, Xia Y, Yan Z, Wang K, Shi L, Shen F. Effectiveness of repeat hepatic resection for patients with recurrent intrahepatic cholangiocarcinoma: Factors associated with long-term outcomes. Surgery 2017; 161:897-908. [DOI: 10.1016/j.surg.2016.10.024] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 09/23/2016] [Accepted: 10/18/2016] [Indexed: 12/19/2022]
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19
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Rahnemai-Azar AA, Pandey P, Kamel I, Pawlik TM. Monitoring outcomes in intrahepatic cholangiocarcinoma patients following hepatic resection. Hepat Oncol 2017; 3:223-239. [PMID: 30191045 DOI: 10.2217/hep-2016-0009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/04/2016] [Indexed: 02/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is one of the fatal gastrointestinal cancers with increasing incidence and mortality. Although surgery offers the only potential for cure in iCCA patients, the prognosis is not optimal with low overall survival rate and high disease recurrence. Hence, adjuvant therapy is generally recommended in the management of high-risk patients. Identifying factors associated with disease recurrence and survival of the iCCA patients after resection will improve understanding of disease prognosis and help in selecting patients who will benefit from surgical resection or stratifying them for clinical trials. Despite development of new methods for early detection of tumor recurrence, effective prognostic models and nomograms, and recent advances in management, significant challenges remain in improving the prognosis of iCCA patients.
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Affiliation(s)
- Amir A Rahnemai-Azar
- Department of Surgery, University of Washington Medical Center, University of Washington School of Medicine, Seattle, WA, USA.,Department of Surgery, University of Washington Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Pallavi Pandey
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ihab Kamel
- Department of Radiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Radiology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, OH, USA.,Department of Surgery, Wexner Medical Center, Ohio State University, Columbus, OH, USA
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20
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Luvira V, Eurboonyanun C, Bhudhisawasdi V, Pugkhem A, Pairojkul C, Luvira V, Sathitkarnmanee E, Somsap K, Kamsa-ard S. Patterns of Recurrence after Resection of Mass-Forming Type
Intrahepatic Cholangiocarcinomas. Asian Pac J Cancer Prev 2016; 17:4735-4739. [PMID: 27893205 PMCID: PMC5454625 DOI: 10.22034/apjcp.2016.17.10.4735] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background: Intrahepatic cholangiocarcinoma (IHCCA) is an aggressive tumor for which surgical resection is
a mainstay of treatment. However, recurrence after resection is common associated with a poor prognosis. Studies
regarding recurrence of mass-forming IHCCA are rare; therefore, we investigated the pattern with our dataset. Methods:
We retrospectively reviewed the medical and pathological records of 50 mass-forming IHCCA patients who underwent
hepatic resection between January 2004 and December 2009 in order to determine the patterns of recurrence and
prognosis. All demographic and operative parameters were analyzed for their effects on recurrence-free survival.
Results: The median recurrence-free survival time was 188 days (95%CI: 149-299). The respective 1-, 2-, and 3-year
recurrence-free survival rates were 16.2% (95%CI: 6.6-29.4), 5.4% (95%CI: 1.0-15.8) and 2.7% (95%CI: 0.2-12.0).
There was an equal distribution of recurrence at solitary and multiple sites. Univariate analysis revealed no factors
related to recurrence-free survival.Conclusion: The overall survival and recurrence-free survival after surgery for
mass-forming IHCCA were found to be very poor. Almost all recurrences were detected within 2 years after surgery.
Adjuvant chemotherapy after surgery may add benefit in the affected patients.
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Affiliation(s)
- Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
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Li B, Tang H, Zhang A, Dong J. Prognostic Role of Mucin Antigen MUC4 for Cholangiocarcinoma: A Meta-Analysis. PLoS One 2016; 11:e0157878. [PMID: 27305093 PMCID: PMC4909222 DOI: 10.1371/journal.pone.0157878] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 06/06/2016] [Indexed: 12/30/2022] Open
Abstract
Background and Objective Surgery carries the best hope for cure in the treatment of cholangiocarcinoma (CC), whereas surgical outcome is not fully satisfactory. Bio-molecular markers have been used to improve tumor staging and prognosis prediction. Mucin antigen MUC4 (MUC4) has been implicated as a marker for poor survival in various tumors. However, prognostic significance of MUC4 for patients with CC remains undefined. The aim of the present meta-analysis was to investigate the association between MUC4 expression and overall survival (OS) of patients with resected CC. Methods The meta-analysis was conducted in adherence to the MOOSE guidelines. PubMed, Embase databases, Cochrane Library and the Chinese SinoMed were systematically searched to identify eligible studies from the initiation of the databases to April, 2016. OSs were pooled by using hazard ratio (HR) with corresponding 95% confidence interval (CI). Random effect models were utilized because of the between-study heterogeneities. Results Five studies reporting on 249 patients were analyzed: 94 (37.75%) were in positive or high expression group and 155 (62.25%) in negative or low expression group. The pooled HR for positive or high expression group was found to be 3.04 (95% CI 2.25–4.12) when compared with negative or low expression group with slight between-study heterogeneities (I2 3.10%, P = 0.39). The result indicated that a positive or high expression level of MUC4 was significantly related to poor survival in patients with resected CC. A commensurate result was identified by sensitivity analysis. The main limitations of the present meta-analysis were the rather small size of the studies included and relatively narrow geographical distribution of population. Conclusion The result of this meta-analysis indicated that a positive or high expression level of MUC4 was significantly related to poor survival in patients with resected CC.
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Affiliation(s)
- Bingmin Li
- Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
| | - Haowen Tang
- Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
| | - Aiqun Zhang
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
| | - Jiahong Dong
- Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Haidian, Beijing, 100853, China
- * E-mail:
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The value of systematic lymph node dissection for intrahepatic cholangiocarcinoma from the viewpoint of liver lymphatics. J Gastroenterol 2015; 50:913-27. [PMID: 25833009 DOI: 10.1007/s00535-015-1071-2] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 03/16/2015] [Indexed: 02/04/2023]
Abstract
Lymph node (LN) metastasis from intrahepatic cholangiocarcinoma (IHCC) might be one of the most important indicators of aggressive surgical resection, yet the value of LN dissection is still controversial. To address this clinical problem, we need to better understand the multidirectional lymphatic outflow from the liver. Although most hepatic lymph flows into the hilar LNs along portal triads, there are also several lymphatic outflows directly communicating with distant areas or the general lymphatic system. Moreover, it has been revealed that LN metastasis spreads to more distal LNs through the hepatoduodenal ligament or other multidirectional lymphatic pathways connected to the general lymphatic system. Therefore, systematic LN dissection might merely be LN sampling in IHCC with LN metastasis. A multidisciplinary strategy focusing on adjuvant treatment after surgery is immediately necessary in these cases. In IHCC without LN metastasis, the accuracy of preoperative imaging assessment of LN metastasis is unsatisfactory and useless for detecting metastatic LNs in clinical settings. Therefore, prophylactic systematic LN dissection for IHCC without preoperative LN swelling is recommended for accurate LN status assessment and reduction of local recurrences. However, this procedure might not offer any clinical benefit according to the results of retrospective comparative studies. In this review, we summarize previous reports regarding lymphatic outflow of the liver and discuss LN dissection for IHCC.
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Tabrizian P, Jibara G, Hechtman JF, Franssen B, Labow DM, Schwartz ME, Thung SN, Sarpel U. Outcomes following resection of intrahepatic cholangiocarcinoma. HPB (Oxford) 2015; 17:344-51. [PMID: 25395176 PMCID: PMC4368399 DOI: 10.1111/hpb.12359] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 09/22/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The aim of this analysis was to examine prognostic features and outcomes in patients undergoing resection for intrahepatic cholangiocarcinoma (ICC). METHODS A retrospective chart review was performed in all patients who underwent R0 or R1 resection for primary ICC between 1995 and 2011. Clinical data were abstracted and statistical analyses were conducted in the standard fashion. RESULTS A total of 82 patients underwent curative hepatectomy for primary ICC; 51 patients in this cohort developed recurrence. The median follow-up of survivors was 27 months (range: 1-116 months). Recurrences were intrahepatic (65%), associated with multiple tumours (54%) and occurred during the first 2 years after hepatectomy (86%). The main factor associated with recurrence after resection was the presence of satellite lesions. Overall 5-year disease-free survival after primary resection was 16%. Factors associated with poor survival were transfusion and perineural invasion. Treatment of recurrence was undertaken in 89% of patients and repeat surgical resection was performed in 15 patients. The 3-year survival rate after recurrence was 25%. Prolonged survival after recurrence was associated with a solitary tumour recurrence. CONCLUSIONS Despite curative resection of ICC, recurrence can be expected to occur in 79% of patients at 5 years. Predictors of survival and recurrence after resection vary in the literature. In patients with recurrence, selection of the optimal treatment remains challenging.
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Affiliation(s)
- Parissa Tabrizian
- Department of Surgery, Division of Surgical Oncology, Mount Sinai Medical CenterNew York, NY, USA,Correspondence, Parissa Tabrizian, Department of Surgery, Mount Sinai Medical Center, 19 East 98th Street, 7th Floor, New York, NY 10029, USA. Tel: + 1 212 241 2891. Fax: + 1 212 241 1572. E-mail:
| | - Ghalib Jibara
- Department of Urology, Brookdale University Hospital and Medical CenterNew York, NY, USA
| | - Jaclyn F Hechtman
- Department of Pathology, Memorial Sloan Kettering Cancer CenterNew York, NY, USA
| | - Bernardo Franssen
- Department of Surgery, Division of Surgical Oncology, Mount Sinai Medical CenterNew York, NY, USA
| | - Daniel M Labow
- Department of Surgery, Division of Surgical Oncology, Mount Sinai Medical CenterNew York, NY, USA
| | - Myron E Schwartz
- Department of Urology, Brookdale University Hospital and Medical CenterNew York, NY, USA
| | - Swan N Thung
- Department of Pathology, Memorial Sloan Kettering Cancer CenterNew York, NY, USA
| | - Umut Sarpel
- Department of Surgery, Division of Surgical Oncology, Mount Sinai Medical CenterNew York, NY, USA
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Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma? A review of 17 years of experience in a tertiary institution. Surgery 2015; 157:666-75. [DOI: 10.1016/j.surg.2014.11.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 09/20/2014] [Accepted: 11/06/2014] [Indexed: 12/30/2022]
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Cholangiocarcinoma. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Cho CS. Prognostication systems as applied to primary and metastatic hepatic malignancies. Surg Oncol Clin N Am 2014; 24:41-56. [PMID: 25444468 DOI: 10.1016/j.soc.2014.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Staging systems are an attempt to incorporate the biology and therapy for cancer in a way that enables categorization and prediction of oncologic outcomes. Because of unusual disease biology and complexities related to treatment intervention, efforts to develop reliable staging systems for hepatic malignancies have been challenging. This article discusses the ways in which improved understanding of these diseases has informed the evolution of prognostication systems as applied to hepatocellular carcinoma, cholangiocarcinoma, and hepatic colorectal adenocarcinoma.
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Affiliation(s)
- Clifford S Cho
- Section of Surgical Oncology, Department of Surgery, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792, USA.
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27
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Amini N, Ejaz A, Spolverato G, Maithel SK, Kim Y, Pawlik TM. Management of lymph nodes during resection of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a systematic review. J Gastrointest Surg 2014; 18:2136-48. [PMID: 25300798 DOI: 10.1007/s11605-014-2667-1] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 09/22/2014] [Indexed: 01/31/2023]
Abstract
The role of lymph node dissection (LND) in the treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to systematically review all available evidence to determine the role of LND in patients with HCC and ICC. Studies that reported on LND, lymph node metastasis (LNM), and short- and long-term outcomes for patients with HCC or ICC survival were identified from PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Data were extracted, synthesized, and analyzed using standard techniques. A total of 603 and 434 references were identified for HCC and ICC, respectively. Among HCC patients, the overall prevalence of LND was 51.6 % (95 % confidence interval (CI) 19.7-83.5) with an associated LNM incidence of 44.5 % (95 % CI 27.4-61.7). LNM was associated with a 3- and 5-year survival of 27.5 and 20.8 %, respectively. Among ICC patients, most patients 78.5 % (95 % CI 76.2-80.7) underwent LND; 45.2 % (95 % CI 39.2-51.2) had LNM. Three and 5-year survival among ICC patients with LNM was 0.2 % (95 % CI 0-0.7) and 0 %, respectively. While there are insufficient data to recommend a routine LND in all patients with HCC or ICC, the potential prognostic value of LND suggests that LND should at least be considered at the time of surgery.
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Affiliation(s)
- Neda Amini
- Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA
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Baheti AD, Tirumani SH, Rosenthal MH, Shinagare AB, Ramaiya NH. Diagnosis and management of intrahepatic cholangiocarcinoma: a comprehensive update for the radiologist. Clin Radiol 2014; 69:e463-70. [PMID: 25240565 DOI: 10.1016/j.crad.2014.08.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Revised: 07/23/2014] [Accepted: 08/06/2014] [Indexed: 01/04/2023]
Abstract
There is increasing focus on intrahepatic cholangiocarcinoma (IHCC) due to its rising incidence worldwide and relatively poor prognosis, with the revised TNM classification (2009) introducing a separate staging system for IHCC for the first time. In this article, we comprehensively review the current role of the radiologist in the diagnosis and management of patients with IHCC.
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Affiliation(s)
- A D Baheti
- Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
| | - S H Tirumani
- Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - M H Rosenthal
- Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - A B Shinagare
- Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - N H Ramaiya
- Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
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High-mobility group AT-hook 2: an independent marker of poor prognosis in intrahepatic cholangiocarcinoma. Hum Pathol 2014; 45:2334-40. [PMID: 25245603 DOI: 10.1016/j.humpath.2014.04.026] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 03/25/2014] [Accepted: 04/02/2014] [Indexed: 12/24/2022]
Abstract
High-mobility group AT-hook 2 (HMGA2) regulates cell growth, differentiation, apoptosis, and neoplastic transformation. Previous studies have shown that malignant tumors expressing HMGA2, such as gastric, lung, and colorectal carcinomas, usually have a poor prognosis. HMGA2 expression and its clinical significance in intrahepatic cholangiocarcinomas have not been studied. We identified 55 intrahepatic cholangiocarcinomas resected at our institution from 1994 to 2003. Hematoxylin-eosin-stained slides were reviewed, and histopathologic characteristics were recorded, including mitotic count, tumor grade, vascular and perineural invasion, lymph node metastasis, and margin status. Using immunohistochemical stains, we examined expression of HMGA2, p53, p16, Kit, α-fetoprotein, and Ki-67, and we analyzed the correlation of survival with clinicopathological characteristics and immunohistochemical findings. Positive staining for HMGA2, p53, p16, Kit, α-fetoprotein, and Ki-67 was seen in 18 (33%), 37 (69%), 26 (47%), 21 (38%), 2 (4%), and 34 (63%) tumors, respectively. HMGA2 expression correlated positively with p53 expression (P = .02; ρ = 0.32) and negatively with p16 expression (P = .04; ρ = -0.28). Univariate analysis showed that HMGA2 expression and lymph node metastasis were associated with shorter patient survival and were independent indicators of poor survival (P = .02 and P = .03, respectively). Tumorigenic effects of HMGA2 in intrahepatic cholangiocarcinoma may partly reflect its ability to negatively regulate expression of p16 tumor suppressors and to be associated with p53 abnormalities.
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Sriputtha S, Khuntikeo N, Promthet S, Kamsa-Ard S. Survival rate of intrahepatic cholangiocarcinoma patients after surgical treatment in Thailand. Asian Pac J Cancer Prev 2014; 14:1107-10. [PMID: 23621195 DOI: 10.7314/apjcp.2013.14.2.1107] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC), one of the primary liver cancers, is frequent in the northeastern part of Thailand. Surgical resection remains the best method of treatment, but patients suffering from ICC usually present at a late stage of the disease. Studies of survival and prognostic factors after surgery remain rare. The aim here was to evaluate the survival rate and factors affecting the survival of patients with intrahepatic cholangiocarcinoma after surgery. The study used a retrospective cohort design. The subjects were 73 consecutive patients with ICC, who were admitted for surgery to Srinagarind Hospital, Khon Kaen University, during the period 2005-2009. The censoring date was 31 December, 2011, data being evaluated using uni- and multivariate analyses. Postoperative survival analysis was performed by the Kaplan-Meier method, and the Cox proportional hazard model was used to identify independent prognostic factors. The total follow-up time was 99 person-years. The total number of deaths was 59, giving a mortality rate of 59 per 100 person-years. The cumulative 1-, 3-, and 5-year survival rates were 52.1%, 21.7%, and 11.2%, respectively. The median duration of survival after resection was 12.4 months. Univariate analysis revealed stage of disease, lymph node metastasis, histological type, histological grade and macroscopic classification to be statistically significant (p-value<0.05) prognostic factors. In the multivariate analysis, only macroscopic classification was statistically significant (p-value<0.05). In conclusion, macroscopic classification was the only independent factor found to be significantly associated with survival following surgical treatment of ICC.
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31
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Surgical treatment for intrahepatic cholangiocarcinoma. Clin J Gastroenterol 2014; 7:87-93. [PMID: 26183622 DOI: 10.1007/s12328-014-0460-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 01/26/2014] [Indexed: 12/15/2022]
Abstract
Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC.
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Li H, Wu JS, Wang XT, Lv P, Gong LS, Liu G, Tian BN, Li YY, Jiang B. Factors predicting surgical resection in patients with intrahepatic cholangiocarcinoma and cirrhosis. J INVEST SURG 2014; 27:219-25. [PMID: 24476002 DOI: 10.3109/08941939.2014.880138] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Here, we investigate the potential factors that affect the outcome of patients with intrahepatic cholangiocarcinomas (ICC) and cirrhosis. We retrospectively reviewed the clinical data and pathological features of 58 patients with ICC and cirrhosis who underwent liver resection between July 2000 and March 2008, and analyzed the prognostic risk factors by means of univariate and multivariate analyses. The overall morbidity and mortality were 40% and 3.3%, respectively. The overall median survival was 24 months, and the 1-, 3-, and 5-year actuarial survival rates were 53%, 18%, and 10%, respectively. Univariate analysis showed that Child-Pugh classification, hypoalbuminemia, vascular invasion, lymphnodes metastasis, tumor-nodes-metastasis (TNM) staging system, positive surgical margins, and high perioperative blood transfusion volumes were all significantly associated with poor survival. Multivariate analysis confirmed that hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volume were survival related, with hazard ratios (HR) of 2.58, 3.12, 3.57, and 1.98, respectively. Surgical resection is an effective treatment for patients affected by ICC and cirrhosis. Predictive factors, including hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volumes are all related to poor survival.
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Affiliation(s)
- Hao Li
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital , Changsha , China
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Murakami S, Ajiki T, Okazaki T, Ueno K, Kido M, Matsumoto I, Fukumoto T, Ku Y. Factors affecting survival after resection of intrahepatic cholangiocarcinoma. Surg Today 2014; 44:1847-54. [PMID: 24452507 DOI: 10.1007/s00595-013-0825-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 09/05/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE This study aimed at assessing the prognostic factors of resection of intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS Among 70 patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45 (64 %) underwent resection and 25 had unresectable tumors. Univariate and multivariate analyses were conducted retrospectively to assess the factors influencing survival of the patients who underwent resection. RESULTS The median survival times of the patients who underwent resection versus those who did not were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis identified residual tumor status (relative risk 4.12, P = 0.04) and pathological differentiation (relative risk 5.55, P = 0.04) as independent factors predicting survival. Patients who underwent R1 resection had a significantly higher rate of local recurrence than those who underwent R0 resection (P = 0.008). With R0 resection, there were no significant differences in patterns and rates of recurrence between patients with narrow (≤ 5 mm) versus wide (>5 mm) surgical margins. CONCLUSIONS R0/1 resection and a well-differentiated tumor were found to be independent prognostic factors for long-term survival after IHCC resection. If R0 resection was achieved, the width of the negative surgical margin did not affect the patterns and rates of recurrence.
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Affiliation(s)
- Sae Murakami
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan,
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Marubashi S, Gotoh K, Takahashi H, Ohigashi H, Yano M, Ishikawa O, Sakon M. Prediction of the postoperative prognosis of intrahepatic cholangiocarcinoma (ICC): importance of preoperatively- determined anatomic invasion level and number of tumors. Dig Dis Sci 2014; 59:201-13. [PMID: 24122559 DOI: 10.1007/s10620-013-2894-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Accepted: 09/17/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Preoperative prediction of the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) following surgical treatment remains quite difficult and controversial. We attempted to identify the preoperative and postoperative predictors of the overall survival rates inpatients with ICC in order to clarify the appropriate indications for surgical resection of ICC. PATIENTS AND METHODS We retrospectively investigated the clinicopathological features of ICC and outcome of surgical resection in 111 consecutive patients who underwent surgical treatment at our hospital between 1980 and March 2012. Both preoperative factors and operatively confirmed factors were evaluated as potential risk factors for determination of the post-surgical prognosis. RESULTS Curative resection (R0) was performed in 72 patients (64.9 %). The 1- and 3-year overall survival rates were 85.0 and 59.7 % in the R0 group. Two preoperative factors [hilar invasion as recognized by computed tomography(HR 3.16, P = 0.020) and multiple intrahepatic tumors (HR 7.09, P = 0.0002)] and two operatively confirmed factors [multiple intrahepatic tumors (HR 9.17,P = 0.0009) and lymph node metastasis as confirmed by final histology (HR 6.41, P = 0.003)] were identified as significant risk factors adversely influencing the overall survival rate after surgery. Furthermore, solitary, small(\5 cm) and peripheral ICCs were associated with a very low probability of lymph node metastasis. CONCLUSIONS Preoperatively diagnosed hilar invasion,multiple intrahepatic tumors and histologically confirmed lymph node metastasis were the main determinants of an adverse postoperative prognosis in patients with ICC.Lymph node dissection could be omitted for patients with solitary, small and peripheral ICCs.
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Li DY, Zhang HB, Yang N, Quan Y, Yang GS. Routine lymph node dissection may be not suitable for all intrahepatic cholangiocarcinoma patients: Results of a monocentric series. World J Gastroenterol 2013; 19:9084-9091. [PMID: 24379635 PMCID: PMC3870563 DOI: 10.3748/wjg.v19.i47.9084] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 10/09/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the indications for lymph node dissection (LND) in intrahepatic cholangiocarcinoma patients.
METHODS: A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma (ICC) patients who had undergone surgical resection of ICC from January 2006 to December 2007. Curative resection was attempted for all patients unless there were metastases to lymph nodes (LNs) beyond the hepatoduodenal ligament. Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases. The patients were classified according to the LND and LN metastases. Clinicopathologic, operative, and long-term survival data were collected retrospectively. The impact on survival of LND during primary resection was analyzed.
RESULTS: Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND, 11 had lymph nodes metastases. Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival (P = 0.822). Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND; their survival curve did not differ significantly from that of the palliative resection group (P = 0.744). However, there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group (median survival time 12 mo vs 6.0 mo, P = 0.013).
CONCLUSION: ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy. Routine LND should be considered with discretion.
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Intrahepatic cholangiocarcinoma: relationship between tumor imaging enhancement by measuring attenuation and clinicopathologic characteristics. ACTA ACUST UNITED AC 2013; 38:785-92. [PMID: 23232581 DOI: 10.1007/s00261-012-9974-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
PURPOSE Arterial enhancement of intrahepatic cholangiocarcinoma (ICC) has been noted. To precisely identify the characteristics of tumor enhancement patterns, we examined the relationship between CT attenuation in the tumor and clinicopathological parameters or prognosis. METHODS Subjects were 42 ICC patients who had undergone hepatectomy. microvessel density (MVD) determined by CD34 staining was compared with imaging. Attenuation was calculated in images from multidetector CT of tumor and non-tumorous regions. Enhancement patterns were divided into two groups: arterial enhancement with higher attenuation (>16 HU; Hyper group, n = 12); and arterial enhancement with lower attenuation (Hypo group, n = 30). RESULTS Univariate analysis identified high tumor marker level, increased size, less-differentiation, incomplete resection, increased bleeding, and lower MVD as significantly associated with poor survival (p < 0.05). Increased attenuation throughout the whole ICC correlated significantly with radiological findings and MVD. Concomitant hepatitis, well-differentiation, and smaller tumor were more significantly frequent in the Hyper group than in the Hypo group (p < 0.05). Postoperative early recurrence was significantly less frequent in the Hyper group, and overall survival was significantly better in the Hyper group (p < 0.05). CONCLUSIONS Increased CT attenuation correlated with ICC tumor vascularity. Increased tumor enhancement in the arterial phase was associated with chronic hepatitis, lower malignancy, and better survival.
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Adachi T, Eguchi S. Lymph node dissection for intrahepatic cholangiocarcinoma: a critical review of the literature to date. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:162-8. [DOI: 10.1002/jhbp.30] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Tomohiko Adachi
- Department of Surgery; Nagasaki University Graduate School of Biomedical Sciences; 1-7-1 Sakamoto Nagasaki 852-8501 Japan
| | - Susumu Eguchi
- Department of Surgery; Nagasaki University Graduate School of Biomedical Sciences; 1-7-1 Sakamoto Nagasaki 852-8501 Japan
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Dodson RM, Weiss MJ, Cosgrove D, Herman JM, Kamel I, Anders R, Geschwind JFH, Pawlik TM. Intrahepatic cholangiocarcinoma: management options and emerging therapies. J Am Coll Surg 2013; 217:736-750.e4. [PMID: 23890842 DOI: 10.1016/j.jamcollsurg.2013.05.021] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Revised: 05/23/2013] [Accepted: 05/24/2013] [Indexed: 12/14/2022]
Affiliation(s)
- Rebecca M Dodson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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Cao J, Huang L, Liu C, Li J, Zhang X, Shen J, Li J, Lu L, Xu F, Yan J, Wu M, Lau WY, Yan Y. Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) in a single patient: a clinicopathologic study of 35 resected cases. J Gastroenterol Hepatol 2013; 28:1025-31. [PMID: 23425127 DOI: 10.1111/jgh.12143] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/17/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Combined hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) coexisting in the liver have rarely been reported before. The aim of this study is to report on the clinicopathological features and prognosis of patients with double hepatic cancer. METHODS The clinicopathologic, perioperative, and long-term survival data of 35 patients who underwent synchronously resection of double hepatic cancer from January 2002 to December 2008 were studied retrospectively. The data were compared with those patients who had pure HCC or ICC during the study period. RESULTS The incidence of double hepatic cancer was 0.25%. The male to female ratio was 4:1. The prevalence of hepatitis B infection was very high (35/35). Simultaneously elevated serum α-fetoprotein and cancer antigen 19-9 levels (10/35) were observed in 10/35 patients. Metastatic lymph nodes with ICC cells were diagnosed in 4 of 35 patients. Only one patient was diagnosed preoperatively with double hepatic cancer of HCC and ICC. The median overall survival (OS) was 18 months, and the 1-year, 3-year, and 5-year OS rates were 60.0%, 28.9%, and 23.1%, respectively. Multivariate analysis indicated that the tumor size of ICC, presence of lymph node metastasis, and histological differentiation of the ICC component were independent risk factors of OS. CONCLUSION Double hepatic cancer of HCC and ICC is very rare with distinctive clinicopathologic features. The prognosis of double hepatic cancer was as poor as pure ICC. The ICC component played a more important role than the HCC component in influencing the prognosis of double hepatic cancer.
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Affiliation(s)
- Jie Cao
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
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Gross pathological classification of peripheral cholangiocarcinoma determines the efficacy of hepatectomy. J Gastroenterol 2013; 48:647-59. [PMID: 23001251 DOI: 10.1007/s00535-012-0666-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 08/14/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Peripheral cholangiocarcinoma (PCC) can be grossly classified as mass-forming (MF), periductal-infiltrating (PI), and intraductal papillary (IP) types. IP-PCC should be distinguished from other types of PCC because patients with IP-PCC have a more favorable prognosis. We hypothesized that gross pathological classification of non-IP-PCC could determine the efficacy of hepatectomy. METHODS We retrospectively reviewed 224 histologically proven PCCs (including 172 PCCs from patients having non-IP type tumors) from patients who underwent hepatectomy between 1977 and 2007. Non-IP-PCCs were further classified as MF, MF mixed with PI (MF-PI), and PI for comparison. RESULTS Of the 224 patients with PCC, 52 had IP-PCC (23.2 %), and 172 had non-IP-PCC (76.8 %). One hundred one of the 172 non-IP-PCC patients had a curative resection (curative resection rate 58.7 %). The follow-up duration ranged from 1.1 to 193.1 months (median 13.4 months). Overall survival (OS) rates for the non-IP-PCC patients at 1 and 5 years were 58.4 and 15.1 %, respectively. Absence of symptoms, lower alkaline phosphatase levels, normal carcinoembryonic antigen (CEA), and presence of MF-type PCC independently and favorably affected OS for the non-IP-PCC patients following hepatectomy. Independent factors favorably predicting OS for the MF-PCC patients were the absence of symptoms, hepatolithiasis, normal CEA levels, successful curative hepatectomy, and negative lymph node metastasis, while for the MF-PI-PCC patients following hepatectomy, one independent factor, successful curative hepatectomy, favorably predicted OS. For the PI-PCC patients, the independent factors favorably predicting OS were normal albumin levels and negative lymph node metastasis. CONCLUSIONS It is important to correctly differentiate between the gross pathological classifications of non-IP-PCC because of their distinct characteristics and outcomes following hepatectomy. Correct gross pathological classification is essential for further translational investigations.
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Park KW, Jung ES, Kim DG, Yoo YK, Hong TH, Lee IS, Koh YH, Kim JH, Lee MA. ERCC1 Can Be a Prognostic Factor in Hilar Cholangiocarcinoma and Extrahepatic Bile Duct Cancer, But Not in Intrahepatic Cholangiocarcinoma. Cancer Res Treat 2013; 45:63-9. [PMID: 23613672 PMCID: PMC3629365 DOI: 10.4143/crt.2013.45.1.63] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 01/24/2013] [Indexed: 12/13/2022] Open
Abstract
PURPOSE There are three types of bile duct cancer, intrahepatic cholangiocarcinoma (ICC), hilar cholangiocarcinoma (HC), and extrahepatic cholangiocarcinoma (EHC). Despite different clinical presentation, the same protocol has been used in treatment of patients with these cancers. We analyzed clinicopathologic findings and protein expression in order to investigate the difference and the specific prognostic factors among these three types of cancers. MATERIALS AND METHODS We conducted a retrospective review of 104 patients diagnosed with bile duct cancer at Seoul St. Mary's Hospital between January 1994 and May 2004. We performed immunohistochemical staining for p53, cyclin D1, thymidine phosphorylase, survivin, and excision repair cross-complementing group 1 (ERCC1). RESULTS Of the 104 patients, EHC was most common (44.2%). In pathologic findings, perineural invasion was significantly less common in ICC. Overall survival was similar among the three types of cancer. Lymph node invasion, lymphatic, and venous invasion showed a significant association with survival outcome in ICC, however, the differentiation of histologic grade had prognostic significance in HC and EHC. No difference in protein expression was observed among these types of cancer, however, ERCC1 showed a significant association with survival outcome in HC and EHC, not in ICC. CONCLUSION Based on our data, ICC showed different characteristics and prognostic factors, separate from the other two types of bile duct cancer. Conduct of further studies with a large sample size is required in order to confirm these data.
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Affiliation(s)
- Kyun Woo Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Korea
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Kang Y, Lee JM, Kim SH, Han JK, Choi BI. Intrahepatic mass-forming cholangiocarcinoma: enhancement patterns on gadoxetic acid-enhanced MR images. Radiology 2012; 264:751-60. [PMID: 22798225 DOI: 10.1148/radiol.12112308] [Citation(s) in RCA: 140] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate the enhancement patterns of intrahepatic mass-forming cholangiocarcinomas (IMCCs) with emphasis on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS This retrospective study was institutional review board approved, and the requirement for informed consent was waived. Fifty patients (41 men, nine women; mean age, 62.3 years; range, 44-76 years) with IMCC underwent unenhanced and gadoxetic acid-enhanced T1- and T2-weighted MR imaging including dynamic phase and hepatobiliary phase imaging between May 2008 and December 2010. Signal intensity and enhancement patterns of lesions were compared with those of the liver parenchyma in each phase. Conspicuity and margin sharpness of lesions on dynamic phase and HBP images were rated on a 4- or 5-point scale and compared by using the Wilcoxon signed-rank test. Percentage of relative enhancement was compared among pathologic subgroups by using the unpaired Student t test. RESULTS On dynamic phase images, 29 of 48 (60%) lesions showed a thin peripheral rim with centripetal or gradual progression. On HBP images, 48 of 50 (96%) IMCCs were hypointense, and two of 50 (4%) were hyperintense. Subjective ratings of conspicuity and margin sharpness were significantly higher on HBP (median scores, 5 and 4, respectively) (P < .001) than on the dynamic phase (median scores, 4 and 3, respectively) images (P < .001). Additional daughter nodules were found in five patients and intrahepatic metastasis was found in one. Percentage of relative enhancement on HBP images was significantly higher in moderately differentiated (66.4% ± 42.1) than in poorly differentiated (36.84% ± 21.5) tumors (P = .039) and in patients without (59.7% ± 28.8) than in those with (24.9% ± 14.7) (P = .036) lymph node metastasis. CONCLUSION The most prevalent enhancement pattern on gadoxetic acid-enhanced MR images of IMCCs was a thin peripheral rim with internal heterogeneous enhancement during the dynamic phase. HBP images showed increased lesion conspicuity and better delineation of daughter nodules and intrahepatic metastasis, which may aid in the diagnosis of IMCC.
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Affiliation(s)
- Yusuhn Kang
- Department of Radiology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea
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Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2012; 25:603-8. [PMID: 22059167 DOI: 10.1155/2011/917097] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision. OBJECTIVE To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration. METHODS Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration. RESULTS Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level greater than 37 U⁄mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, respectively. CONCLUSIONS The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.
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Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg 2012; 254:824-29; discussion 830. [PMID: 22042474 DOI: 10.1097/sla.0b013e318236c21d] [Citation(s) in RCA: 183] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Define the optimal surgical margin in patients undergoing surgery for intrahepatic cholangiocarcinoma (IHCC). BACKGROUND DATA Surgery is the most effective treatment for IHCC. However, the influence of R1 resection on outcome is controversial and that of margin width has not been evaluated. METHODS We studied 212 patients undergoing curative resection of mass-forming-type IHCC. The respective influences on survival of resection status (R0 vs R1), surgical margin width, pTNM stage, and the latter's components were evaluated. RESULTS Incidence of R1 resection was 24%. Overall, R1 resection was not an independent predictor of survival [odds ratio (OR) 1.2 (0.7-2.1)] in contrast to the pTNM stage [OR 2.10 (1.2-3.5)]. In the 78 pN+ patients, survival was similar after R0 and R1 resections (median: 18 vs 13 months, respectively, P = 0.1). In the 134 pN0 patients, R1 resection was an independent predictor of poor survival [OR 9.6 (4.5-20.4)], as was the presence of satellite nodules [OR 1.9 (1.1-3.2)]. In the 116 pN0 patients with R0 resections, median survival was correlated with margin width (≤1 mm: 15 months; 2-4 mm: 36 months; 5-9 mm: 57 month; ≥10 mm: 64 month, P < 0.001) and a margin >5 mm was an independent predictor of survival [OR 2.22 (1.59-3.09)]. CONCLUSION Patients undergoing surgery for IHCC are at high risk of R1 resections. In pN0 patients, R1 resection is the strongest independent predictor of poor outcome and a margin of at least 5 mm should be created. The survival benefits of resection in pN+ patients and R1 resection in general are very low.
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Clinical impact of lymph node dissection in surgery for peripheral-type intrahepatic cholangiocarcinoma. Surg Today 2011; 42:147-51. [PMID: 22124809 DOI: 10.1007/s00595-011-0057-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Accepted: 02/07/2011] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations. METHODS Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis. RESULTS Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups. CONCLUSIONS Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.
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Igami T, Ebata T, Yokoyama Y, Sugawara G, Takahashi Y, Nagino M. Staging of Peripheral-Type Intrahepatic Cholangiocarcinoma: Appraisal of the New TNM Classification and its Modifications. World J Surg 2011; 35:2501-9. [DOI: 10.1007/s00268-011-1242-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Yamamoto M, Ariizumi SI. Surgical outcomes of intrahepatic cholangiocarcinoma. Surg Today 2011; 41:896-902. [PMID: 21748603 DOI: 10.1007/s00595-011-4517-z] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Accepted: 01/23/2011] [Indexed: 12/19/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is considered to be a fatal disease because of frequent recurrence despite curative surgery. The macroscopic classification of ICC in the General Rules for the Clinical and Pathological Study of Primary Liver Cancer of the Liver Cancer Study Group of Japan reflects tumor-spreading patterns; therefore, the clinicopathological findings and surgical outcomes can be predicted using this classification. Lymph node and intrahepatic metastases, and a curative resection are important prognostic factors in ICC; however, lymph node dissection is still controversial. In particular, the intraductal growth type and periductal infiltrating type of ICC without hilar invasion have favorable surgical outcomes, whereas the mass-forming type and periductal infiltrating type of ICC with hilar invasion have high hepatic recurrence and local recurrence, respectively. Multimodal treatments are therefore needed to improve the surgical outcomes of ICC.
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Affiliation(s)
- Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada, Shinjuku-ku, Tokyo, 162-8666, Japan
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Prognostic value of cirrhosis for intrahepatic cholangiocarcinoma after surgical treatment. J Gastrointest Surg 2011; 15:608-13. [PMID: 21246412 DOI: 10.1007/s11605-011-1419-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Accepted: 01/05/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND The surgical outcome and prognostic factors of intrahepatic cholangiocarcinoma are not fully understood. This study aimed to establish the clinical significance of cirrhosis for prognosis in patients with intrahepatic cholangiocarcinoma after surgery. METHODS One hundred fifteen patients with intrahepatic cholangiocarcinoma who underwent surgical resection between December 2001 and January 2008 were retrospectively analyzed. The prognostic significance of clinicopathologic factors including cirrhosis was assessed by univariate and multivariate analyses. RESULTS Thirty-two of the 115 patients (28%) had liver cirrhosis. Complete tumor removal (R0 resection) was performed in 42 patients (75%). Overall median survival time was 21 months, with 1-, 3-, and 5-year actuarial survival rates of 68%, 27%, and 17%, respectively. There was a significant difference in survival between patients with cirrhosis and those without cirrhosis (P = 0.027). Univariate analysis showed that cirrhosis, vascular invasion, hepatic duct invasion, lymph node metastasis, positive surgical margin (R1), and TNM stage were significantly associated with poor survival. Multivariate analysis showed that cirrhosis, positive surgical margin, and lymph node metastases were related to survival, with hazard ratios of 2.49, 3.53, and 4.16, respectively. CONCLUSIONS Cirrhosis is an independent factor for poor prognosis in intrahepatic cholangiocarcinoma after surgery.
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Abstract
Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the bile ducts, arising from malignant transformation of the epithelial cells that line the biliary apparatus. ICC is relatively uncommon, but its incidence is on the increase. ICC is frequently discovered as an incidental, indeterminate liver mass. Surgical resection of ICC represents the only potentially curative therapeutic option. The role of routine hilar lymphadenectomy is controversial, but should be considered to optimize staging. Although adjuvant chemotherapy and radiotherapy is probably not supported by current data, each should strongly be considered in patients with lymph node metastasis or an R1 resection. For those patients with inoperable disease, locoregional therapy with transarterial chemoembolization can be considered.
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Affiliation(s)
- George A Poultsides
- Department of Surgery, Division of Surgical Oncology, Stanford University School of Medicine, 300 Pasteur drive, H3680, Stanford, CA 94305-5641, USA
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Intrahepatic cholangiocarcinoma: primary liver resection and aggressive multimodal treatment of recurrence significantly prolong survival. Ann Surg 2010; 252:107-14. [PMID: 20531002 DOI: 10.1097/sla.0b013e3181e462e6] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the results of surgical therapy for intrahepatic cholangiocarcinoma (ICC), the incidence and the management of recurrence, and to analyze the change in approach during 2 different periods. DESIGN Retrospective study. PATIENTS AND METHODS Patient and tumor characteristics, and overall and disease-free survival were analyzed in a series of 72 consecutive patients who underwent hepatic resection for ICC. Several factors likely to influence survival after resection were evaluated. Patients were divided into 2 groups according to the year of operation (before and after 1999). Management of recurrence and survival after recurrence were also analyzed. RESULTS The 3- and 5-year overall survival rates were 62% and 48%, whereas the 3- and 5-year disease-free survival rates were 30% and 25%, respectively. The median survival time was 57.1 months. Patient and histologic characteristics before and after 1999 were similar. Survival was significantly better among patients operated after 1999, who were node-negative, did not receive blood transfusion, and underwent adjuvant chemotherapy. The overall recurrence rates before and after 1999 were comparable (66.6% and 50%, P = 0.49). The most frequent site of recurrence was the liver. A significantly large number of patients received treatment for recurrence after 1999 (81.5%) compared with the first period (8.3%). The overall 3-year survival rate after recurrence was 46%. After 1999, there was a significant improvement in 3-year survival after recurrence (56%) compared with patients operated before 1999 (0%, P = 0.004); the median survival time from the diagnosis of recurrence increased from 20 months to 66 months in the second group. CONCLUSIONS Although recurrence rate represents a frequent problem in ICC, an aggressive approach to recurrence can significantly prolong survival.
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