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1
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Soliman N, Maqsood A, Connor AA. Role of genomics in liver transplantation for cholangiocarcinoma. Curr Opin Organ Transplant 2025; 30:158-170. [PMID: 39917813 DOI: 10.1097/mot.0000000000001209] [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: 03/06/2025]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the current knowledge of cholangiocarcinoma molecular biology and to suggest a framework for implementation of next-generation sequencing in all stages of liver transplantation. This is timely as recent guidelines recommend increased use of these technologies with promising results. RECENT FINDINGS The main themes covered here address germline and somatic genetic alterations recently discovered in cholangiocarcinoma, particularly those associated with prognosis and treatment responses, and nascent efforts to translate these into contemporary practice in the peri-liver transplantation period. SUMMARY Early efforts to translate molecular profiling to cholangiocarcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking is a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care with the ambition of increasing the number of patients eligible for liver transplantation and improving their long-term outcomes.
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Affiliation(s)
- Nadine Soliman
- Department of Surgery
- J. C. Walter Jr. Transplant Center, Houston Methodist Hospital
- Houston Methodist Academic Institute
| | - Anaum Maqsood
- Department of Medicine
- Neill Cancer Center, Houston Methodist Hospital, Houston, Texas
| | - Ashton A Connor
- Department of Surgery
- J. C. Walter Jr. Transplant Center, Houston Methodist Hospital
- Houston Methodist Academic Institute
- Neill Cancer Center, Houston Methodist Hospital, Houston, Texas
- Department of Surgery, Weill Cornell Medicine, Cornell University, New York, New York, USA
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Tsai YC, Huang CJ, Chang JL, Chiang NJ, Huang YS, Bandaru A, Hung SC, Shan YS, Lee GB. Application of CAPTURE Assay for Early Diagnosis and Prognosis in Bile and Blood of Cholangiocarcinoma. JCO Precis Oncol 2025; 9:e2400728. [PMID: 40153686 DOI: 10.1200/po-24-00728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/17/2025] [Accepted: 02/19/2025] [Indexed: 03/30/2025] Open
Abstract
PURPOSE Cholangiocarcinoma (CCA) is highly metastatic, difficult to diagnose, and characterized by extremely low 5-year survival rate. Liquid biopsy is reported as a new tool for monitoring and potential diagnosis of cancers. In this study, we developed a novel approach, CAPTURE (Cancer cell affinity probing and tracked by immunoreaction) assay, using blood and bile for the detection of CCA. MATERIALS AND METHODS The CAPTURE assay isolated exfoliated tumor cells (ETCs) from bile and circulating tumor cells (CTCs) from blood of patients with CCA (CCA+) using magnetic beads coated with two affinity probes: a nucleic-acid aptamer or a glycosaminoglycan octasaccharide, followed by immunostaining to track target tumor cells-bead complexes. Target-bead complexes were quantified under a fluorescent microscope (ETCs:CK17+/CK7+/Hoechst+; CTCs: CK17+/CD45-/Hoechst+). Epithelial cell adhesion molecule was also used as a comparison. The blood and bile from patients of benign biliary-related diseases (CCA-) served as control. The study was validated in a single-blind fashion. RESULTS Finally, numbers of CTCs of blood (82 CCA+ and 48 CCA-) and ETCs of bile (132 CCA+ and 63 CCA-) samples were quantified and validated. Sensitivities and specificities were 98.5% and 85.7% with bile tests, and 96.3% and 85.4% with blood tests. Moreover, we successfully monitored prognoses of two follow-up patients using CAPTURE assay after treatments. CONCLUSION ETCs in bile could be promising indicators of disease status in early through advanced stages of CCA, whereas CTCs in blood might have crucial value in diagnosing and monitoring advanced stages of CCA. Our results showed that the CAPTURE assay would be a powerful tool in CCA diagnostics and prognostics.
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Affiliation(s)
- Yi-Cheng Tsai
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Chien-Jui Huang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jui-Lin Chang
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Nai-Jung Chiang
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Shan Huang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Shang-Cheng Hung
- Genomics Research Centre, Academia Sinica, Taipei, Taiwan
- Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
| | - Yan-Shen Shan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Gwo-Bin Lee
- Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
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Fahrmann JF, Yip-Schneider M, Vykoukal J, Spencer R, Dennison JB, Do KA, Long JP, Maitra A, Zhang J, Schmidt CM, Hanash S, Irajizad E. Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing. Cancer Lett 2025; 612:217450. [PMID: 39793753 DOI: 10.1016/j.canlet.2025.217450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/06/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method. We demonstrated improvements in AUC estimates (2-13 %) for all biomarkers when considering the PEB approach compared to ST. For CA19-9, the PEBCA19-9 yielded an AUC of 0.88 when at least one repeat measurement was within 3 years of clinical diagnosis. At a specificity of 98.5 %, the PEBCA19-9 identified 15 of the 41 PDAC cases and signaled positive at an average lead-time of 1.09 years whereas the ST approach captured 11 of the 41 PDAC cases with an average positive signal at 0.48 years. Among CA19-9 low individuals, a PEB algorithm based on repeat measurements of TIMP1 yielded an additional 14 % sensitivity at 98.5 % specificity. An adaptive algorithm that considers repeated CA19-9 measurements improves sensitivity and lead-time detection of PDAC compared to a single-threshold method. Additional protein biomarkers may improve sensitivity for earlier detection of PDAC among cases with low CA19-9.
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Affiliation(s)
- Johannes F Fahrmann
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Jody Vykoukal
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rachelle Spencer
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jennifer B Dennison
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kim-Anh Do
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030
| | - James P Long
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030
| | - Anirban Maitra
- Department of Translational Molecular Pathology and Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030
| | - Jianjun Zhang
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Samir Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Ehsan Irajizad
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 77030.
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4
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Roth GS, Verlingue L, Sarabi M, Blanc JF, Boleslawski E, Boudjema K, Bretagne-Bignon AL, Camus-Duboc M, Coriat R, Créhange G, De Baere T, de la Fouchardière C, Dromain C, Edeline J, Gelli M, Guiu B, Horn S, Laurent-Croise V, Lepage C, Lièvre A, Lopez A, Manfredi S, Meilleroux J, Neuzillet C, Paradis V, Prat F, Ronot M, Rosmorduc O, Cunha AS, Soubrane O, Turpin A, Louvet C, Bouché O, Malka D. Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT). Eur J Cancer 2024; 202:114000. [PMID: 38493667 DOI: 10.1016/j.ejca.2024.114000] [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: 12/11/2023] [Revised: 02/28/2024] [Accepted: 03/01/2024] [Indexed: 03/19/2024]
Abstract
INTRODUCTION This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.
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Affiliation(s)
- Gael S Roth
- Univ. Grenoble Alpes / Hepato-Gastroenterology and Digestive Oncology department, CHU Grenoble Alpes / Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, Grenoble, France
| | - Loic Verlingue
- Medical Oncology Department, Centre Léon Bérard, 28 rue Laennec, Lyon, France
| | - Matthieu Sarabi
- Gastroenterology Department, Hopital privé Jean Mermoz, 69008 Lyon, France
| | | | - Emmanuel Boleslawski
- Univ. Lille, INSERM U1189, CHU Lille, Service de Chirurgie Digestive et Transplantations, Lille, France
| | - Karim Boudjema
- Département de chirurgie viscérale hépatobiliaire, CHU de Rennes, Rennes, France
| | | | - Marine Camus-Duboc
- Endoscopie digestive, Hôpital Saint-Antoine, AP-HP/Sorbonne Université, Paris France
| | - Romain Coriat
- Service de gastroentérologie, d'endoscopie et d'oncologie digestive, Hôpital Cochin, APHP, Paris, France
| | - Gilles Créhange
- Radiation Oncology Department. Paris/Saint-Cloud/Orsay, Institut Curie. PSL Research University, Paris, France
| | - Thierry De Baere
- Département de Radiologie Interventionnelle, Gustave Roussy, 94805 Villejuif, France
| | | | - Clarisse Dromain
- Service de radiodiagnostic et radiologie interventionnelle, Centre Hospitalier Universitaire Vaudois, Switzerland
| | | | - Maximiliano Gelli
- Département de Chirurgie Viscérale, Gustave Roussy, 94805 Villejuif, France
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital - Montpellier School of Medicine, Montpellier, France
| | - Samy Horn
- Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Pierre Benite, France
| | - Valérie Laurent-Croise
- Department of Radiology, Centre Hospitalier Universitaire de Nancy, Hôpital de Brabois, 54500 Vandœuvre-lès-Nancy, France
| | - Côme Lepage
- Université de Bourgogne, CHU Dijon-Bourgogne, INSERM U1231. BP 87 900, 14 rue Paul Gaffarel, 21079 Dijon, France
| | - Astrid Lièvre
- Department of Gastroenterology, Rennes University Hospital, University of Rennes 1, INSERM Unité 1242, Rennes, France
| | - Anthony Lopez
- INSERM U1256, NGERE, Faculty of Medicine, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France; Department of Hepatology and Gastroenterology, Nancy University Hospital, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France, NGERE, Faculty of Medicine, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Sylvain Manfredi
- Université de Bourgogne, CHU Dijon-Bourgogne, INSERM U1231. BP 87 900, 14 rue Paul Gaffarel, 21079 Dijon, France
| | - Julie Meilleroux
- Pathology and Cytology Department, CHU Toulouse, IUCT Oncopole, Toulouse Cedex 9, France
| | - Cindy Neuzillet
- GI Oncology, Department of Medical Oncology, Institut Curie - Site Saint Cloud, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France
| | - Valérie Paradis
- Université Paris Cité, APHP.Nord Sce d'Anatomie Pathologique Hôpital Beaujon, Clichy, INSERM UMR 1149, France
| | - Frédéric Prat
- Endoscopie digestive, Hôpital Beaujon, Clichy, France
| | - Maxime Ronot
- Department of Medical Imaging, Beaujon University Hospital, Clichy, France
| | - Olivier Rosmorduc
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM U1193, Université Paris-Saclay, FHU Hépatinov, France
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM U1193, Université Paris-Saclay, FHU Hépatinov, France
| | - Olivier Soubrane
- Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Anthony Turpin
- Department of Medical Oncology, CNRS UMR9020, Inserm UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University Lille, CHU Lille, Lille; GERCOR, Paris, France
| | - Christophe Louvet
- Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France
| | - Olivier Bouché
- Gastroenterology and Digestive Oncology Department, Robert-Debré University Hospital, Reims, France
| | - David Malka
- Department of Medical Oncology, Institute Mutualiste Montsouris, Paris, France.
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Lee SH, Song SY. Recent Advancement in Diagnosis of Biliary Tract Cancer through Pathological and Molecular Classifications. Cancers (Basel) 2024; 16:1761. [PMID: 38730713 PMCID: PMC11083053 DOI: 10.3390/cancers16091761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/24/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Biliary tract cancers (BTCs), including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a diverse group of cancers that exhibit unique molecular characteristics in each of their anatomic and pathological subtypes. The pathological classification of BTCs compromises distinct growth patterns, including mass forming, periductal infiltrating, and intraductal growing types, which can be identified through gross examination. The small-duct and large-duct types of intrahepatic cholangiocarcinoma have been recently introduced into the WHO classification. The presentation of typical clinical symptoms, as well as the extensive utilization of radiological, endoscopic, and molecular diagnostic methods, is thoroughly detailed in the description. To overcome the limitations of traditional tissue acquisition methods, new diagnostic modalities are being explored. The treatment landscape is also rapidly evolving owing to the emergence of distinct subgroups with unique molecular alterations and corresponding targeted therapies. Furthermore, we emphasize the crucial aspects of diagnosing BTC in practical clinical settings.
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Affiliation(s)
- Sang-Hoon Lee
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Republic of Korea;
| | - Si Young Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03772, Republic of Korea
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6
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Kikuchi Y, Shimada H, Yamasaki F, Yamashita T, Araki K, Horimoto K, Yajima S, Yashiro M, Yokoi K, Cho H, Ehira T, Nakahara K, Yasuda H, Isobe K, Hayashida T, Hatakeyama S, Akakura K, Aoki D, Nomura H, Tada Y, Yoshimatsu Y, Miyachi H, Takebayashi C, Hanamura I, Takahashi H. Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2. Int J Clin Oncol 2024; 29:512-534. [PMID: 38493447 DOI: 10.1007/s10147-024-02497-0] [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: 01/31/2024] [Accepted: 02/21/2024] [Indexed: 03/19/2024]
Abstract
In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.
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Affiliation(s)
| | - Hideaki Shimada
- Department of Clinical Oncology, Toho University, Tokyo, Japan.
- Department of Surgery, Toho University, Tokyo, Japan.
| | - Fumiyuki Yamasaki
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Taku Yamashita
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Koji Araki
- Department of Otorhinolaryngology-Head and Neck Surgery, National Defense Medical College, Saitama, Japan
| | - Kohei Horimoto
- Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | - Masakazu Yashiro
- Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Keigo Yokoi
- Department of Lower Gastrointestinal Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takuya Ehira
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazunari Nakahara
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Hiroshi Yasuda
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazutoshi Isobe
- Division of Respiratory Medicine, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
| | - Tetsu Hayashida
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | | | - Daisuke Aoki
- International University of Health and Welfare Graduate School, Tokyo, Japan
| | - Hiroyuki Nomura
- Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Aichi, Japan
| | - Yuji Tada
- Department of Pulmonology, School of Medicine, International University of Health and Welfare, Chiba, Japan
| | - Yuki Yoshimatsu
- Department of Patient-Derived Cancer Model, Tochigi Cancer Center Research Institute, Tochigi, Japan
| | - Hayato Miyachi
- Faculty of Clinical Laboratory Sciences, Nitobe Bunka College, Tokyo, Japan
| | - Chiaki Takebayashi
- Division of Hematology and Oncology, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
| | - Ichiro Hanamura
- Division of Hematology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan
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Sun Y, Gong J, Li Z, Han L, Sun D. Gallbladder cancer: surgical treatment, immunotherapy, and targeted therapy. Postgrad Med 2024; 136:278-291. [PMID: 38635593 DOI: 10.1080/00325481.2024.2345585] [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: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 04/20/2024]
Abstract
Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.
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Affiliation(s)
- Yanjun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | - Junfeng Gong
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | | | - Lin Han
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | - Dengqun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
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8
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Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
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Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
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9
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Saca D, Flamm SL. Cholangiocarcinoma Surveillance Recommendations in Patients with Primary Sclerosing Cholangitis. Clin Liver Dis 2024; 28:183-192. [PMID: 37945159 DOI: 10.1016/j.cld.2023.07.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Cholangiocarcinoma (CCA) is a deadly complication observed in the setting of primary sclerosing cholangitis (PSC). When symptoms develop and CCA is diagnosed, it is usually at an advanced stage. Median survival is less than 12 months. Early identification of CCA leads to improved outcomes. Although diagnostic tests have excellent specificity, they are plagued by low sensitivity. No surveillance strategies have been widely agreed upon, but most societies recommend measurement of serum carbohydrate antigen 19-9 and MRCP every 6 to 12 months in patients with PSC. Advances in understanding of the genetic factors that lead to CCA are awaited.
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Affiliation(s)
- Daniel Saca
- Rush University Medical School, 1725 West Harrison Street Suite 110, Chicago, IL 60612, USA
| | - Steven L Flamm
- Rush University Medical School, 1725 West Harrison Street Suite 110, Chicago, IL 60612, USA.
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10
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van Keulen AM, Olthof PB, Buettner S, Bednarsch J, Verheij J, Erdmann JI, Nooijen LE, Porte RJ, Minnee RC, Murad SD, Neumann UP, Heij L, Groot Koerkamp B, Doukas M. The Influence of Hepatic Steatosis and Fibrosis on Postoperative Outcomes After Major Liver Resection of Perihilar Cholangiocarcinoma. Ann Surg Oncol 2024; 31:133-141. [PMID: 37899413 PMCID: PMC10695871 DOI: 10.1245/s10434-023-14419-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023]
Abstract
BACKGROUND Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.
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Affiliation(s)
| | - Pim B Olthof
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Stefan Buettner
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Joanne Verheij
- Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Joris I Erdmann
- Department of Surgery, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Lynn E Nooijen
- Department of Surgery, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Robert J Porte
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Robert C Minnee
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Ulf P Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
| | - Lara Heij
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
- Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
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11
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Dolbnya AD, Popov IA, Pekov SI. Molecular Biomarkers in Cholangiocarcinoma: Focus on Bile. Curr Top Med Chem 2024; 24:722-736. [PMID: 38303538 DOI: 10.2174/0115680266290367240130054142] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/12/2024] [Accepted: 01/17/2024] [Indexed: 02/03/2024]
Abstract
Hepatobiliary system cancers have demonstrated an increasing incidence rate in the past years. Without the presence of early symptoms, the majority of such cancers manifest with a set of similar symptoms, such as cholestasis resulting in posthepatic icterus. Differential diagnosis of hepatobiliary cancers is required for the therapy selection, however, the similarity of the symptoms complicates diagnostics. Thus, the search for molecular markers is of high interest for such patients. Cholangiocarcinoma (CCA) is characterized by a poor prognosis due to a low resectability rate, which occurs because this disease is frequently beyond the limits of surgical therapy at the time of diagnosis. The CCA is diagnosed by the combination of clinical/biochemical features, radiological methods, and non-specific serum tumor biomarkers, although invasive examination is still needed. The main disadvantage is limited specificity and sensitivity, which complicates early diagnostics. Therefore, prognostic and predictive biomarkers are still lacking and urgently needed for early diagnosis. In contrast to serum, bile is more accessible to identify biliary disease due to its simpler composition. Moreover, bile can contain higher concentrations of tumor biomarkers due to its direct contact with the tumor. It is known that the composition of the main bile component - bile acids, may vary during different diseases of the biliary tract. This review summarizes the recent developments in the current research on the diagnostic biomarkers for CCA in serum and bile and provides an overview of the methods of bile acids analysis.
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Affiliation(s)
- Andrey D Dolbnya
- Siberian State Medical University, Tomsk, 634050, Russian Federation
| | - Igor A Popov
- Siberian State Medical University, Tomsk, 634050, Russian Federation
- Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russian Federation
| | - Stanislav I Pekov
- Siberian State Medical University, Tomsk, 634050, Russian Federation
- Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russian Federation
- Skolkovo Institute of Science and Technology, Moscow, 121205, Russian Federation
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12
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Esteban JG, Muñoz-Antolí C, Toledo R, Ash LR. Diagnosis of Human Trematode Infections. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1454:541-582. [PMID: 39008275 DOI: 10.1007/978-3-031-60121-7_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]
Abstract
Digenetic trematodes form a major group of human parasites, affecting a large number of humans, especially in endemic foci. Over 100 species have been reported infecting humans, including blood, lung, liver and intestinal parasites. Traditionally, trematode infections have been diagnosed by parasitological methods based on the detection and the identification of eggs in different clinical samples. However, this is complicated due to the morphological similarity between eggs of different trematode species and other factors such as lack of sensitivity or ectopic locations of the parasites. Moreover, the problem is currently aggravated by migratory flows, international travel, international trade of foods and changes in alimentary habits. Although efforts have been made for the development of immunological and molecular techniques, the detection of eggs through parasitological techniques remains as the gold standard for the diagnosis of trematodiases. In the present chapter, we review the current status of knowledge on diagnostic techniques used when examining feces, urine, and sputum and also analyze the most relevant characteristics used to identify eggs with a quick key for the identification of eggs.
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Affiliation(s)
- J Guillermo Esteban
- Área de Parasitología, Departamento de Farmacia, Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universidad de Valencia, Burjassot, Valencia, Spain.
| | - Carla Muñoz-Antolí
- Área de Parasitología, Departamento de Farmacia, Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universidad de Valencia, Burjassot, Valencia, Spain
| | - Rafael Toledo
- Área de Parasitología, Departamento de Farmacia, Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universidad de Valencia, Burjassot, Valencia, Spain
| | - Lawrence R Ash
- Infectious & Tropical Diseases, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA
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13
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Catanzaro E, Gringeri E, Burra P, Gambato M. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies. Cancers (Basel) 2023; 15:4947. [PMID: 37894314 PMCID: PMC10604939 DOI: 10.3390/cancers15204947] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2-8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. A complex combination of molecular mechanisms involving inflammatory pathways, direct cytopathic damage, and epigenetic and genetic alterations are involved in cholangiocytes carcinogenesis. The insidious clinical presentation makes early detection difficult, and the integration of biochemical, radiological, and histological features does not always lead to a definitive diagnosis of PSC-CCA. Surveillance is mandatory, but current guideline strategies failed to improve early detection and consequently a higher patient survival rate. MicroRNAs (miRNAs), gene methylation, proteomic and metabolomic profile, and extracellular vesicle components are some of the novel biomarkers recently applied in PSC-CCA detection with promising results. The integration of these new molecular approaches in PSC diagnosis and monitoring could contribute to new diagnostic and surveillance strategies.
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Affiliation(s)
- Elisa Catanzaro
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Patrizia Burra
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Martina Gambato
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
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14
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Yıldırım HÇ, Kavgaci G, Chalabiyev E, Dizdar O. Advances in the Early Detection of Hepatobiliary Cancers. Cancers (Basel) 2023; 15:3880. [PMID: 37568696 PMCID: PMC10416925 DOI: 10.3390/cancers15153880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/23/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.
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Affiliation(s)
| | | | | | - Omer Dizdar
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey; (H.Ç.Y.); (G.K.); (E.C.)
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15
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Ong KH, Lai HY, Sun DP, Chen TJ, Huang SKH, Tian YF, Chou CL, Shiue YL, Chan TC, Li CF, Kuo YH. Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma. FRONT BIOSCI-LANDMRK 2023; 28:75. [PMID: 37114547 DOI: 10.31083/j.fbl2804075] [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: 12/24/2022] [Revised: 03/03/2023] [Accepted: 03/27/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. METHODS We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. RESULTS TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. CONCLUSIONS Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.
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Affiliation(s)
- Khaa Hoo Ong
- Division of Gastroenterology & General Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, Taiwan
- Department of Medical Technology, Chung Hwa University of Medical Technology, 717 Tainan, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-sen University, 804 Kaohsiung, Taiwan
| | - Hong-Yue Lai
- Department of Pharmacology, School of Medicine, China Medical University, 404333 Taichung, Taiwan
| | - Ding-Ping Sun
- Division of Gastroenterology & General Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, Taiwan
| | - Tzu-Ju Chen
- Department of Medical Technology, Chung Hwa University of Medical Technology, 717 Tainan, Taiwan
- Department of Clinical Pathology, Chi Mei Medical Center, 710 Tainan, Taiwan
| | - Steven Kuan-Hua Huang
- Division of Urology, Department of Surgery, Chi Mei Medical Center, 710 Tainan, Taiwan
- Department of Medical Science Industries, College of Health Sciences, Chang Jung Christian University, 711 Tainan, Taiwan
| | - Yu-Feng Tian
- Division of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, Taiwan
| | - Chia-Lin Chou
- Department of Medical Technology, Chung Hwa University of Medical Technology, 717 Tainan, Taiwan
- Division of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, Taiwan
| | - Yow-Ling Shiue
- Institute of Biomedical Sciences, National Sun Yat-sen University, 804 Kaohsiung, Taiwan
- Institute of Precision Medicine, National Sun Yat-sen University, 804 Kaohsiung, Taiwan
| | - Ti-Chun Chan
- Department of Medical Research, Chi Mei Medical Center, 710 Tainan, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, 704 Tainan, Taiwan
| | - Chien-Feng Li
- Institute of Precision Medicine, National Sun Yat-sen University, 804 Kaohsiung, Taiwan
- Department of Medical Research, Chi Mei Medical Center, 710 Tainan, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, 704 Tainan, Taiwan
- Trans-Omic Laboratory for Precision Medicine, Chi Mei Medical Center, 710 Tainan, Taiwan
| | - Yu-Hsuan Kuo
- Institute of Biomedical Sciences, National Sun Yat-sen University, 804 Kaohsiung, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, 71004 Tainan, Taiwan
- College of Pharmacy and Science, Chia Nan University, 71710 Tainan, Taiwan
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16
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Hu C, Iyer RK, Juran BD, McCauley BM, Atkinson EJ, Eaton JE, Ali AH, Lazaridis KN. Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data. BMC Gastroenterol 2023; 23:129. [PMID: 37076803 PMCID: PMC10114387 DOI: 10.1186/s12876-023-02759-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 04/06/2023] [Indexed: 04/21/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) patients have a risk of developing cholangiocarcinoma (CCA). Establishing predictive models for CCA in PSC is important. METHODS In a large cohort of 1,459 PSC patients seen at Mayo Clinic (1993-2020), we quantified the impact of clinical/laboratory variables on CCA development using univariate and multivariate Cox models and predicted CCA using statistical and artificial intelligence (AI) approaches. We explored plasma bile acid (BA) levels' predictive power of CCA (subset of 300 patients, BA cohort). RESULTS Eight significant risk factors (false discovery rate: 20%) were identified with univariate analysis; prolonged inflammatory bowel disease (IBD) was the most important one. IBD duration, PSC duration, and total bilirubin remained significant (p < 0.05) with multivariate analysis. Clinical/laboratory variables predicted CCA with cross-validated C-indexes of 0.68-0.71 at different time points of disease, significantly better compared to commonly used PSC risk scores. Lower chenodeoxycholic acid, higher conjugated fraction of lithocholic acid and hyodeoxycholic acid, and higher ratio of cholic acid to chenodeoxycholic acid were predictive of CCA. BAs predicted CCA with a cross-validated C-index of 0.66 (std: 0.11, BA cohort), similar to clinical/laboratory variables (C-index = 0.64, std: 0.11, BA cohort). Combining BAs with clinical/laboratory variables leads to the best average C-index of 0.67 (std: 0.13, BA cohort). CONCLUSIONS In a large PSC cohort, we identified clinical and laboratory risk factors for CCA development and demonstrated the first AI based predictive models that performed significantly better than commonly used PSC risk scores. More predictive data modalities are needed for clinical adoption of these models.
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Affiliation(s)
- Chang Hu
- Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL, 61801, USA
| | - Ravishankar K Iyer
- Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL, 61801, USA
| | - Brian D Juran
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Bryan M McCauley
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 55905, USA
| | - Elizabeth J Atkinson
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 55905, USA
| | - John E Eaton
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Ahmad H Ali
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
- Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO, 65212, USA
| | - Konstantinos N Lazaridis
- Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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17
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Lee S, Kim H, Sohn H, Lee M, Jung H, Jo Y, Han Y, Kwon W, Jang JY. The Optimal Cutoff Value of Tumor Markers for Prognosis Prediction in Ampullary Cancer. Cancers (Basel) 2023; 15:cancers15082281. [PMID: 37190211 DOI: 10.3390/cancers15082281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/03/2023] [Accepted: 04/11/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND Carbohydrate antigen 19-9 (CA 19-9) is a representative tumor marker used for the diagnosis of pancreatic and biliary tract cancers. There are few published research results that can be applied to actual clinical practice for ampullary cancer (AC) alone. This study aimed to demonstrate the relationship between the prognosis of AC and the level of CA 19-9, and to determine the optimal thresholds. METHODS Patients who underwent curative resection (pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD)) for AC at the Seoul National University Hospital between January 2000 and December 2017 were enrolled. To determine the optimal cutoff values that could clearly stratify the survival outcome, the conditional inference tree (C-tree) method was used. After obtaining the optimal cutoff values, they were compared to the upper normal clinical limit of 36 U/mL for CA 19-9. Results In total, 385 patients were enrolled in this study. The median value of the tumor marker CA 19-9 was 18.6 U/mL. Using the C-tree method, 46 U/mL was determined to be the optimal cutoff value for CA 19-9. Histological differentiation, N stage, and adjuvant chemotherapy were significant predictors. CA 19-9 36 U/mL had marginal significance as a prognostic factor. In contrast, the new cutoff value, CA 19-9 46 U/mL, was found to be a statistically significant prognostic factor (HR: 1.37, p = 0.048). CONCLUSIONS The new cutoff value of CA 19-9 46 U/mL may be used for evaluating the prognosis of AC. Therefore, it may be an effective indicator for determining treatment strategies such as surgical treatments and adjuvant chemotherapy.
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Affiliation(s)
- Seungho Lee
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Hongbeom Kim
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Heeju Sohn
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Mirang Lee
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Hyesol Jung
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Youngjae Jo
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Youngmin Han
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Wooil Kwon
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Jin-Young Jang
- Departments of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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Duggan WP, Brosnan C, Christodoulides N, Nolan N, Kambakamba P, Gallagher TK. Outruling cholangiocarcinoma in patients with primary sclerosing cholangitis wait-listed for liver transplantation: A report on the Irish national experience. Surgeon 2023; 21:e83-e88. [PMID: 35680491 DOI: 10.1016/j.surge.2022.05.005] [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: 09/19/2021] [Revised: 05/05/2022] [Accepted: 05/18/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND The presence of diffuse biliary stricturing in Primary Sclerosing Cholangitis (PSC) makes the diagnosis of early Cholangiocarcinoma (CCA) in this context difficult. A finding of incidental CCA on liver explant is associated with poor oncological outcomes, despite this; there remains no international consensus on how best to outrule CCA in this group ahead of transplantation. The objectives of this study were to report the Irish incidence of incidental CCA in individuals with PSC undergoing liver transplantation, and to critically evaluate the accuracy of diagnostic modalities in outruling CCA in our wait-listed PSC cohort. METHODS We conducted a retrospective analysis of our prospectively maintained database, which included all PSC patients wait-listed for liver transplant in Ireland. RESULTS 4.41% of patients (n = 3) were found to have an incidental finding of CCA on liver explant. Despite only being performed in 35.06% of wait-listed PSC patients (n = 27), Endoscopic Retrograde Cholangiopancreatogram (ERCP) with brush cytology was found to be the most effective tool in correctly outruling CCA in this context; associated with a specificity of 96.15%. CONCLUSION Our findings support a future role for routine surveillance of PSC patients awaiting liver transplantation; however further research is required in order to identify which investigative modalities are of optimal diagnostic utility in this specific context.
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Affiliation(s)
- William P Duggan
- Department of Hepatobiliary and Transplant Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland; Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
| | - Conor Brosnan
- Department of Hepatobiliary and Transplant Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland; Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | | | - Niamh Nolan
- Department of Pathology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland
| | - Patryk Kambakamba
- Department of Hepatobiliary and Transplant Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Tom K Gallagher
- Department of Hepatobiliary and Transplant Surgery, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland
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19
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Villard C, Friis-Liby I, Rorsman F, Said K, Warnqvist A, Cornillet M, Kechagias S, Nyhlin N, Werner M, Janczewska I, Hagström T, Nilsson E, Bergquist A. Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis. J Hepatol 2023; 78:604-613. [PMID: 36410555 DOI: 10.1016/j.jhep.2022.11.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND & AIMS The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort. METHODS In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression. RESULTS Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n = 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01). CONCLUSION In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted. IMPACT AND IMPLICATIONS A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.
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Affiliation(s)
- Christina Villard
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | | | - Fredrik Rorsman
- Department of Hepatology, Akademiska University Hospital, Uppsala, Sweden
| | - Karouk Said
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Warnqvist
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Martin Cornillet
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Stergios Kechagias
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Nils Nyhlin
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Mårten Werner
- Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | | | - Therese Hagström
- Department of Gastroenterology, Stockholm South General Hospital, Stockholm, Sweden
| | - Emma Nilsson
- Gastroenterology Clinic, Skåne University Hospital, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
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20
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Cadamuro M, Al-Taee A, Gonda TA. Advanced endoscopy meets molecular diagnosis of cholangiocarcinoma. J Hepatol 2023; 78:1063-1072. [PMID: 36740048 DOI: 10.1016/j.jhep.2023.01.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/22/2022] [Accepted: 01/18/2023] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. We present our diagnostic and theranostic approach to the initial evaluation of cholangiocarcinomas, focusing on extrahepatic cholangiocarcinoma. This involves a multipronged strategy incorporating advanced imaging, endoscopic methods, multiple approaches to tissue sampling, and molecular markers. We also provide an algorithm for the sequential use of these tools.
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Affiliation(s)
| | - Ahmad Al-Taee
- Carle Illinois College of Medicine, University of Illinois Urbaba-Champaign, Champaign County, IL, USA
| | - Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University, New York, NY, USA.
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21
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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22
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Diagnosis of Cholangiocarcinoma. Diagnostics (Basel) 2023; 13:diagnostics13020233. [PMID: 36673043 PMCID: PMC9858255 DOI: 10.3390/diagnostics13020233] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Cholangiocarcinoma (CCA), a tumor of the bile duct epithelium, is increasing in incidence. CCA remains a highly fatal malignancy because early diagnosis is difficult. Based on its anatomical location, CCA can be categorized into the following three groups: perihilar, intrahepatic, and extrahepatic. Patients with CCA complain of asymptomatic jaundice, weight loss, and right upper quadrant abdominal discomfort. Imaging modalities, including transabdominal ultrasound, computed tomography, and magnetic resonance imaging, play an important role in detecting tumors as well as guiding biopsy procedures and staging workups in CCA. Characteristically, extrahepatic CCA shows abrupt changes in ductal diameter with upstream ductal dilation. Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are recommended as the next step in the evaluation of extrahepatic CCA. Tissue is obtained through EUS-FNA or ERCP (biopsy, brush cytology), and therapeutic intervention (such as stent insertion) is performed with ERCP. Moreover, several serum tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen) can be useful in diagnosing CCA in some patients.
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23
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Bergquist A, Weismüller TJ, Levy C, Rupp C, Joshi D, Nayagam JS, Montano-Loza AJ, Lytvyak E, Wunsch E, Milkiewicz P, Zenouzi R, Schramm C, Cazzagon N, Floreani A, Liby IF, Wiestler M, Wedemeyer H, Zhou T, Strassburg CP, Rigopoulou E, Dalekos G, Narasimman M, Verhelst X, Degroote H, Vesterhus M, Kremer AE, Bündgens B, Rorsman F, Nilsson E, Jørgensen KK, von Seth E, Cornillet Jeannin M, Nyhlin N, Martin H, Kechagias S, Wiencke K, Werner M, Beretta-Piccoli BT, Marzioni M, Isoniemi H, Arola J, Wefer A, Söderling J, Färkkilä M, Lenzen H. Impact on follow-up strategies in patients with primary sclerosing cholangitis. Liver Int 2023; 43:127-138. [PMID: 35535655 PMCID: PMC10084018 DOI: 10.1111/liv.15286] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/22/2022] [Accepted: 05/06/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND & AIMS Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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Affiliation(s)
- Annika Bergquist
- Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,European Reference Network for Hepatological Diseases, Stockholm, Sweden
| | - Tobias J Weismüller
- Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami, Florida, USA.,Schiff Center for Liver Diseases, University of Miami, Florida, USA
| | - Christian Rupp
- Department of Gastroenterology, Infectious Diseases, Intoxication, Heidelberg University Hospital, Heidelberg, Germany
| | - Deepak Joshi
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | | | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ellina Lytvyak
- Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Ewa Wunsch
- Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland
| | - Piotr Milkiewicz
- Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.,Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland
| | - Roman Zenouzi
- Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nora Cazzagon
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.,European Reference Network on Hepatological Disease, European Reference Network for Hepatological Diseases, Azienda Ospedaliera-Università di Padova, Padova, Italy
| | - Annarosa Floreani
- Studiosa Senior University of Padova, Italy and Scientific Consultant IRCCS Negrar, Verona, Italy
| | - Ingalill Friis Liby
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Miriam Wiestler
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,European Reference Network for Hepatological Diseases, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,European Reference Network for Hepatological Diseases, Hannover, Germany
| | - Taotao Zhou
- Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany
| | - Eirini Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - George Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | | | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.,Ghent Liver Research Center, Ghent University, Ghent, Belgium.,European Reference Network for Hepatological Diseases, Ghent, Belgium
| | - Helena Degroote
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.,Ghent Liver Research Center, Ghent University, Ghent, Belgium.,European Reference Network for Hepatological Diseases, Ghent, Belgium
| | - Mette Vesterhus
- Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway
| | - Andreas E Kremer
- Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany.,Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Bennet Bündgens
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Fredrik Rorsman
- Department of Gastroenterology and Hepatology, University Hospital, Uppsala, Sweden
| | - Emma Nilsson
- Department of Clinical Sciences, Lund University, Lund, Sweden.,Gastroenterology Clinic, Skåne University Hospital, Sweden
| | | | - Erik von Seth
- Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,European Reference Network for Hepatological Diseases, Stockholm, Sweden
| | - Martin Cornillet Jeannin
- Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Nils Nyhlin
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Harry Martin
- Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, UK
| | - Stergios Kechagias
- Unit of Internal Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Kristine Wiencke
- Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Mårten Werner
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | | | - Marco Marzioni
- Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti - University Hospital, Ancona, Italy
| | - Helena Isoniemi
- Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland
| | - Johanna Arola
- Department of Pathology and Huslab, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Agnes Wefer
- Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Söderling
- Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Martti Färkkilä
- Clinic of Gastroenterology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Henrike Lenzen
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,European Reference Network for Hepatological Diseases, Hannover, Germany.,Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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24
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He S, Zeng F, Yin H, Wang P, Bai Y, Song Q, Chu J, Huang Z, Liu Y, Liu H, Chen Q, Liu L, Zhou J, Hu H, Li X, Li T, Wang G, Cai J, Jiao Y, Zhao H. Molecular diagnosis of pancreatobiliary tract cancer by detecting mutations and methylation changes in bile samples. EClinicalMedicine 2023; 55:101736. [PMID: 36425869 PMCID: PMC9678809 DOI: 10.1016/j.eclinm.2022.101736] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Patients with pancreatobiliary tract cancer usually have a poor clinical outcome, with a 5-year overall survival rate below 20%. This is mainly associated with the late diagnosis. In addition, the standard-of-care for patients with malignant biliary stenosis involves a major surgery, the Whipple procedure. An accurate preoperative diagnosis, including differentiation from benign diseases, is critical to avoid unnecessary treatment. Here we developed BileScreen, a sensitive detection modality for the diagnosis of pancreatobiliary tract cancer based on massively parallel sequencing mutation and methylation changes in bile samples. METHODS A total of 338 patients, from five hospitals in China, with pancreatobiliary system disorders were enrolled in this study between November 2018 and October 2020, and 259 were included for the analysis of BileScreen. We profiled 23 gene mutations and 44 genes with methylation modifications in parallel from bile samples, and set up a model for the detection of malignancy based on multi-level biomarkers. FINDINGS We applied the BileScreen assay in a training cohort (n = 104) to set up the model and algorithm. The model was further evaluated in a validation cohort (n = 105), resulting in 92% sensitivity and 98% specificity. The performance of BileScreen was further assessed in a prospective test cohort (n = 50) of patients diagnosed with suspicious or negative pathology by endoscopic retrograde cholangiopancreatography and were confirmed in follow-up. BileScreen yielded 90% sensitivity and 80% specificity, and outcompeted serum carbohydrate antigen 19-9 in detecting pancreatobiliary tract cancer in all three cohorts, especially in terms of specificity. INTERPRETATION Taken together, BileScreen has the ability to interrogate mutations and methylation changes in bile samples in parallel, thus rendering it a potentially sensitive detection method to help in the diagnosis of pancreatobiliary tract cancer in a safe, convenient and less-invasive manner. FUNDING This study was supported by the Capital's Funds for Health Improvement and Research (2020-2-4025 to S.H.), the National Natural Science Foundation of China (81972311 to H.Z.), CAMS Innovation Fund for Medical Sciences (CIFMS) (2017-12M-4-002 to H.Z.), the CAMS Innovation Fund for Medical Sciences(CIFMS) (2021-I2M-1-066 to CJQ), the Non-profit Central Research Institution Fund of Chinese Academy of Medical Sciences (2019PT310026 to H.Z.) and Sanming Project of Medicine in Shenzhen (SZSM202011010 to H.Z.).
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Affiliation(s)
- Shun He
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fanxin Zeng
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan province, China
| | - Huihui Yin
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pei Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yinlei Bai
- Jinchenjunchuang Clinical Laboratory, Hangzhou, Zhejiang, China
| | - Qianqian Song
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiangtao Chu
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yumeng Liu
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Liu
- Department of Hepatobiliary Surgery, Dazhou Central Hospital, Dazhou, Sichuan province, China
| | - Qichen Chen
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Liu
- Jinchenjunchuang Clinical Laboratory, Hangzhou, Zhejiang, China
| | - Jun Zhou
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan province, China
| | - Hanjie Hu
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xingchen Li
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tengyan Li
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guiqi Wang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Corresponding author. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan South Lane, Chaoyang District, Beijing, China.
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Corresponding author. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan South Lane, Chaoyang District, Beijing, China.
| | - Yuchen Jiao
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Corresponding author. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan South Lane, Chaoyang District, Beijing, China.
| | - Hong Zhao
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Gene Editing Screening and R＆D of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Corresponding author. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan South Lane, Chaoyang District, Beijing, China.
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25
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Kamp EJCA, Dinjens WNM, Doukas M, van Marion R, Verheij J, Ponsioen CY, Bruno MJ, Groot Koerkamp B, Trivedi PJ, Peppelenbosch MP, de Vries AC. Genetic alterations during the neoplastic cascade towards cholangiocarcinoma in primary sclerosing cholangitis. J Pathol 2022; 258:227-235. [PMID: 35897137 PMCID: PMC9825993 DOI: 10.1002/path.5994] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 06/29/2022] [Accepted: 07/25/2022] [Indexed: 01/11/2023]
Abstract
Carcinogenesis of primary sclerosing cholangitis (PSC)-associated cholangiocarcinoma (CCA) is largely unexplored. Improved understanding of the molecular events involved may guide development of novel avenues for rational clinical management. We aimed to assess the genetic alterations during progression of the neoplastic cascade from biliary dysplasia towards CCA in PSC. Forty-four resection specimens or biopsies of PSC patients with biliary dysplasia (n = 2) and/or CCA (n = 42) were included. DNA was extracted from sections of formalin-fixed paraffin-embedded tissue blocks with dysplasia (n = 23), CCA (n = 69), and nonneoplastic tissue (n = 28). A custom-made next-generation sequencing (NGS) panel of 28 genes was used for mutation and copy number variation (CNV) detection. In addition, CNVs of CDKN2A, EGFR, MCL1, and MYC were examined by fluorescence in situ hybridization. Alterations in 16 low-grade dysplasia samples included loss of FGFR1 (19%), CDKN2A (13%), and SMAD4 (6%), amplification of FGFR3 (6%), EGFR (6%), and ERBB2 (6%), and mutations in SMAD4 (13%). High-grade dysplasia (n = 7) is characterized by MYC amplification (43%), and mutations in ERBB2 (71%) and TP53 (86%). TP53 mutations are the most common aberrations in PSC-CCA (30%), whereas mutations in KRAS (16%), GNAS (14%), and PIK3CA (9%) are also common. In conclusion, PSC-CCA exhibits a variety of genetic alterations during progression of the neoplastic cascade, with mainly CNVs being present early, whereas mutations in ERBB2, TP53, and KRAS appear later in the development of CCA. These findings are promising for the development of NGS-guided diagnostic strategies in PSC-CCA. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Eline JCA Kamp
- Department of Gastroenterology and Hepatology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Winand NM Dinjens
- Department of Pathology, Erasmus MC Cancer InstituteUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC Cancer InstituteUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Ronald van Marion
- Department of Pathology, Erasmus MC Cancer InstituteUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Joanne Verheij
- Department of Pathology, Amsterdam UMCUniversity Medical Center AmsterdamRotterdamThe Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMCUniversity Medical Center AmsterdamRotterdamThe Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Palak J Trivedi
- National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology ResearchUniversity of BirminghamBirminghamUK
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands
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26
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Kwon BS, Kim ES, Lim SY, Song MJ, Kim YW, Kim HJ, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee CT, Lee JH. The significance of elevated tumor markers among patients with interstitial lung diseases. Sci Rep 2022; 12:16702. [PMID: 36202924 PMCID: PMC9537420 DOI: 10.1038/s41598-022-20683-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 09/16/2022] [Indexed: 12/03/2022] Open
Abstract
The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271–4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.
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Affiliation(s)
- Byoung Soo Kwon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Sun Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Yoon Lim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Myung Jin Song
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yeon Wook Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Jun Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yeon Joo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Sun Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Young-Jae Cho
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Ho Il Yoon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Choon-Taek Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Ho Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Korea. .,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
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27
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Brown ZJ, Patwardhan S, Bean J, Pawlik TM. Molecular diagnostics and biomarkers in cholangiocarcinoma. Surg Oncol 2022; 44:101851. [PMID: 36126350 DOI: 10.1016/j.suronc.2022.101851] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 08/26/2022] [Accepted: 09/09/2022] [Indexed: 10/14/2022]
Abstract
Regardless of anatomic origin, cholangiocarcinoma is generally an aggressive malignancy with a relatively high case fatality. Surgical resection with curative intent remains the best opportunity to achieve meaningful long-term survival. Most patients present, however, with advanced disease and less than 20% of patients are candidates for surgical resection. Unfortunately, even patients who undergo resection have a 5-year survival that ranges from 20 to 40%. Biomarkers are indicators of normal, pathologic, or biologic responses to an intervention and can range from a characteristic (i.e., blood pressure reading which can detect hypertension) to specific genetic mutations or proteins (i.e., carcinoembryonic antigen level). Novel biomarkers and improved molecular diagnostics represent an attractive opportunity to improve detection as well as to identify novel therapeutic targets for patients with cholangiocarcinoma. We herein review the latest advances in molecular diagnostics and biomarkers related to the early detection and treatment of patients with cholangiocarcinoma.
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Affiliation(s)
- Zachary J Brown
- Department of Surgery, The State Wexner Medical Center, Columbus, OH, USA.
| | - Satyajit Patwardhan
- Dept of HPB Surgery and Liver Transplantation, Global Hospital, Mumbai, India
| | - Joal Bean
- Department of Surgery, The State Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The State Wexner Medical Center, Columbus, OH, USA.
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28
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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29
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Bao F, Liu J, Chen H, Miao L, Xu Z, Zhang G. Diagnosis Biomarkers of Cholangiocarcinoma in Human Bile: An Evidence-Based Study. Cancers (Basel) 2022; 14:cancers14163921. [PMID: 36010914 PMCID: PMC9406189 DOI: 10.3390/cancers14163921] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 11/23/2022] Open
Abstract
Simple Summary A liquid biopsy has the characteristics of low trauma and easy acquisition in the diagnosis of cholangiocarcinoma. Many researchers try to find diagnostic or prognostic biomarkers of CCA through blood, urine, bile and other body fluids. Due to the close proximity of bile to the lesion and the stable nature, bile gradually comes into people’s view. The evaluation of human bile diagnostic biomarkers is not only to the benefit of screening more suitable clinical markers but also of exploring the pathological changes of the disease. Abstract Cholangiocarcinoma (CCA) is a multifactorial malignant tumor of the biliary tract, and the incidence of CCA is increasing in recent years. At present, the diagnosis of CCA mainly depends on imaging and invasive examination, with limited specificity and sensitivity and late detection. The early diagnosis of CCA always faces the dilemma of lacking specific diagnostic biomarkers. Non-invasive methods to assess the degree of CAA have been developed throughout the last decades. Among the many specimens looking for CCA biomarkers, bile has gotten a lot of attention lately. This paper mainly summarizes the recent developments in the current research on the diagnostic biomarkers for CCA in human bile at the levels of the gene, protein, metabolite, extracellular vesicles and volatile organic compounds.
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Affiliation(s)
- Fang Bao
- Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian 116011, China
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
| | - Jiayue Liu
- Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian 116011, China
| | - Haiyang Chen
- Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian 116011, China
| | - Lu Miao
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
| | - Zhaochao Xu
- CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
- Correspondence: (Z.X.); (G.Z.)
| | - Guixin Zhang
- Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China
- Department of General Surgery, Pancreatic-Biliary Center, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian 116011, China
- Correspondence: (Z.X.); (G.Z.)
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30
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Brown ZJ, Hewitt DB, Pawlik TM. Biomarkers of intrahepatic cholangiocarcinoma: diagnosis and response to therapy. FRONT BIOSCI-LANDMRK 2022; 27:85. [PMID: 35345317 DOI: 10.31083/j.fbl2703085] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/31/2022] [Accepted: 02/10/2022] [Indexed: 01/03/2025]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer behind hepatocellular carcinoma (HCC) and carries a dismal prognosis. Improved genetic analysis has paved the way for a better understanding of the distinct somatic genomic landscapes of ICC. The use of next generation sequencing has paved the way for more personalized medicine through identifying unique mutations which may prove to be therapeutic targets. The ability to identify biomarkers specific to ICC will assist in establishing a diagnosis, monitoring response to therapy, as well as assist in identifying novel therapies and personalized medicine. Herein, we discuss potential biomarkers for ICC and how these markers can assist in diagnosis, monitor response to therapy, and potentially identify novel interventions for the treatment of ICC.
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Affiliation(s)
- Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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31
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Zhu S, Liu C, Dong Y, Shao J, Liu B, Shen J. A Retrospective Study of Lenvatinib Monotherapy or Combined With Programmed Cell Death Protein 1 Antibody in the Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma in China. Front Oncol 2022; 11:788635. [PMID: 34976828 PMCID: PMC8718677 DOI: 10.3389/fonc.2021.788635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 11/30/2021] [Indexed: 01/27/2023] Open
Abstract
Lenvatinib has been ratified as a first-line medication for advanced liver tumors by the American Food and Drug Administration. To assess the effectiveness and security of Lenvatinib in the Chinese population in a real-world setting, we enrolled 48 patients with unresectable liver cancer, managed from December 2018 to March 2021. Among them, 9 and 39 (83.30% men) patients had intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), respectively. Twenty-one (43.75%) patients had progressive disease after first-line treatment, and others (56.25%) had not receiving systemic treatment. Lenvatinib was administered alone or in combination with a programmed cell death protein 1 antibody (anti-PD-1). Treatment duration, median progression-free survival (mPFS), and median overall survival (mOS) were examined. The mOS and mPFS were 22.43 and 8.93 months, respectively. Of HCC patients treated with Lenvatinib only, the mOS and mPFS were 22.43 and 11.60 months, respectively. The corresponding values for HCC cases managed with anti-PD-1 combined with Lenvatinib were 21.77 and 7.10 months, respectively. ICC patients did not reach the mOS and their mPFS was 8.63 months. The present findings support the efficacy and security of Lenvatinib in the real-world therapy of Chinese patients with unresectable liver cancer.
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Affiliation(s)
- Sihui Zhu
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.,Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Chenxi Liu
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Yanbing Dong
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Jie Shao
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.,Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Baorui Liu
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.,Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Jie Shen
- Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.,Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
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32
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Hewitt DB, Brown ZJ, Pawlik TM. Surgical management of intrahepatic cholangiocarcinoma. Expert Rev Anticancer Ther 2021; 22:27-38. [PMID: 34730474 DOI: 10.1080/14737140.2022.1999809] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) incidence continues to rise worldwide, and overall survival remains poor. Complete surgical resection remains the only opportunity for cure in patients with ICC yet only one-third of patients present with resectable disease. AREAS COVERED While the low incidence rate of ICC hinders accrual of patients to large, randomized control trials, larger database and long-term institutional studies provide evidence to guide surgical management of ICC. These studies demonstrate feasibility, safety, and efficacy of aggressive surgical management in appropriately selected patients with ICC. Recent advances in the management of ICC, with a focus on surgical considerations, are reviewed. EXPERT OPINION Historically, little progress has been made in the management of ICC with stagnant mortality rates and poor long-term outcomes. However, regionalization of care to centers with experienced multidisciplinary teams, advances in minimally invasive surgical techniques, discovery and development of targeted and immunotherapy agents, and combination locoregional and systemic therapies offer signs of progress in the management of ICC.
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Affiliation(s)
- D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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33
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Serifis N, Tsilimigras DI, Cloonan DJ, Pawlik TM. Challenges and Opportunities for Treating Intrahepatic Cholangiocarcinoma. Hepat Med 2021; 13:93-104. [PMID: 34754247 PMCID: PMC8572023 DOI: 10.2147/hmer.s278136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/22/2021] [Indexed: 12/29/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.
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Affiliation(s)
- Nikolaos Serifis
- Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA
| | | | - Daniel J Cloonan
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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34
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Montano-Loza AJ, Allegretti JR, Cheung A, Ebadi M, Jones D, Kerkar N, Levy C, Rizvi S, Vierling JM, Alvarez F, Bai W, Gilmour S, Gulamhusein A, Guttman O, Hansen BE, MacParland S, Mason A, Onofrio F, Santamaria P, Stueck A, Swain M, Vincent C, Ricciuto A, Hirschfield G. Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver. CANADIAN LIVER JOURNAL 2021; 4:401-425. [PMID: 35989897 PMCID: PMC9235119 DOI: 10.3138/canlivj-2021-0006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 02/09/2021] [Indexed: 11/20/2022]
Abstract
Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Jessica R Allegretti
- Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Angela Cheung
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | - Maryam Ebadi
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - David Jones
- Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Nanda Kerkar
- Division of Gastroenterology, Hepatology and Nutrition, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, New York, USA
| | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami, Miami, Florida, USA
| | - Sumera Rizvi
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Fernando Alvarez
- Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
| | - Wayne Bai
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Susan Gilmour
- Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada
| | - Aliya Gulamhusein
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Orlee Guttman
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
| | - Bettina E Hansen
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Sonya MacParland
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Mason
- Division of Gastroenterology and Liver Unit, University of Alberta, Edmonton, Alberta, Canada
| | - Fernanda Onofrio
- Ajmera Family Transplant Centre, Toronto General Research Institute, Departments of Laboratory Medicine and Pathobiology and Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Pere Santamaria
- Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada
| | - Ashley Stueck
- Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Mark Swain
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Catherine Vincent
- Department of Medicine, University of Montreal, Montreal, Quebec, Canada
| | - Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gideon Hirschfield
- Toronto Centre for Liver Disease, University Health Network & Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
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Saffioti F, Mavroeidis VK. Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis. World J Gastrointest Oncol 2021; 13:1336-1366. [PMID: 34721770 PMCID: PMC8529934 DOI: 10.4251/wjgo.v13.i10.1336] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/05/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.
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Affiliation(s)
- Francesca Saffioti
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, Oxfordshire, United Kingdom
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital, University College London, London NW3 2QG, United Kingdom
| | - Vasileios K Mavroeidis
- Department of Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
- Department of Transplant Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
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Alali A, Moris M, Martel M, Streutker C, Cirocco M, Mosko J, Kortan P, Barkun A, May GR. Predictors of Malignancy in Patients With Indeterminate Biliary Strictures and Atypical Biliary Cytology: Results From Retrospective Cohort Study. J Can Assoc Gastroenterol 2021; 4:222-228. [PMID: 34617004 PMCID: PMC8489527 DOI: 10.1093/jcag/gwaa043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 03/15/2021] [Indexed: 11/12/2022] Open
Abstract
Background Atypical cellular features are commonly encountered in patients with indeterminate biliary strictures, which are nondiagnostic of malignancy yet cannot rule it out. This study aims to identify clinical features that could discriminate patients with indeterminate biliary strictures and atypical biliary cytology who may harbor underlying malignancy. Methods All patients with an indeterminate biliary stricture and an atypical brush cytology obtained during endoscopic brushings were identified in a large tertiary-care center. Demographical information, clinical data and the final pathological diagnosis were collected. The study cohort was divided based on the final diagnosis into benign and malignant groups. Descriptive and multivariable analyses were performed. Results A total of 151 patients were included in the analysis. Of these, 62.9% were males with mean age of 61.7 ± 16.4 years. Overall, there was an almost equal distribution of patients in the benign and malignant groups. Older age (≥65 years), jaundice, weight loss, intrahepatic biliary and pancreatic duct dilation, double-duct sign and presence of a mass were associated with malignancy in the univariate analysis. However, only older age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 to 1.03), jaundice (OR 3.33, 95% CI 1.11 to 9.98) and presence of a mass (OR 12.10, 95% CI 4.94 to 29.67) were significantly associated with malignancy in the multivariate analysis. High CA19-9 was associated with malignancy only in patients with primary sclerosing cholangitis. Conclusion In patients with indeterminate biliary stricture and atypical brush cytology, older age, jaundice and presence of a mass are significant predictors of malignancy. Patients with such characteristics need prompt evaluation to rule out underlying malignancy.
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Affiliation(s)
- Ali Alali
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.,Haya Al-Habeeb Gastroenterology and Hepatology Center, Mubarak Al-Kabeer Hospital, Jabriya, Kuwait
| | - Maria Moris
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.,Digestive Disease Department, Marqués de Valdecilla University Hospital, Cantabria University, Santander, Spain
| | - Myriam Martel
- Division of Gastroenterology, McGill University Health Center, McGill University, Montreal, Quebec, Canada
| | - Catherine Streutker
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Maria Cirocco
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Jeffrey Mosko
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Paul Kortan
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Alan Barkun
- Division of Gastroenterology, McGill University Health Center, McGill University, Montreal, Quebec, Canada
| | - Gary R May
- The Center for Therapeutic Endoscopy and Endoscopic Oncology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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Shotton R, Lamarca A, Valle J, McNamara MG. Potential utility of liquid biopsies in the management of patients with biliary tract cancers: A review. World J Gastrointest Oncol 2021; 13:1073-1085. [PMID: 34616513 PMCID: PMC8465442 DOI: 10.4251/wjgo.v13.i9.1073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 06/14/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
Biliary tract cancer, comprising gallbladder cancer, cholangiocarcinoma and ampullary cancer, represents a more uncommon entity outside high-endemic areas, though global incidence is rising. The majority of patients present at a late stage, and 5-year survival remains poor. Advanced stage disease is incurable, and though palliative chemotherapy has been shown to improve survival, further diagnostic and therapeutic options are required in order to improve patient outcomes. Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations, attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness. Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic, predictive and prognostic biomarkers. In this review, the current standard of care for patients with biliary tract cancer, future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed. Circulating tumour DNA, circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer. A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.
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Affiliation(s)
- Rohan Shotton
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Juan Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Mairéad G McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
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Next-Generation Biomarkers for Cholangiocarcinoma. Cancers (Basel) 2021; 13:cancers13133222. [PMID: 34203269 PMCID: PMC8269024 DOI: 10.3390/cancers13133222] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/16/2021] [Accepted: 06/22/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Early and non-invasive diagnosis of cholangiocarcinoma (CCA) is still challenging, thus largely contributing to the increased mortality rates observed worldwide. Consequently, several efforts have been made in order to report novel biomarkers for CCA, that would aid on diagnosis and also to predict prognosis and therapy response. We herein aim to provide an in-depth and critical revision on the next-generation biomarkers for CCA that have been recently proposed. Abstract The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.
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Wiecek S, Wojtyniak A, Pindur B, Machnikowska-Sokołowska M, Gruszczyńska K, Grzybowska-Chlebowczyk U. Analysis of the Clinical Course of Primary Sclerosing Cholangitis in Paediatric Population-Single Center Study. ACTA ACUST UNITED AC 2021; 57:medicina57070663. [PMID: 34199130 PMCID: PMC8304821 DOI: 10.3390/medicina57070663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/15/2021] [Accepted: 06/24/2021] [Indexed: 11/25/2022]
Abstract
Background and Objectives: Primary sclerosing cholangitis (PSC) is a rare cholestatic disease of the liver of unknown etiology, severe course and poor prognosis. PSC most often co-occurs with inflammatory bowel diseases (IBD), especially with ulcerative colitis (UC). The aim of the study was the analysis of the clinical course of primary sclerosing cholangitis in children, hospitalized in the Gastroenterology Unit in Katowice. Materials and Methods: The analysis included 30 patients, aged from 7 to 18 years, 21/30 boys (70%) and 9/30 girls (30%), diagnosed with PSC in the years 2009–2019. The analysis included the age at diagnosis, clinical symptoms, course of the disease, coexisting diseases, laboratory and imaging results, and complications. Results: The average age at diagnosis was 13 years. 22/30 (73.3%) patients suffered from UC, 4/30 (13.3%) were diagnosed with Crohn’s disease (CD), 2/30 (6.66%) with Eosinophilic Colitis (EC). 2/30 patients (6.66%) had no clinical evidence of coexistent IBD to date. In addition, 7/30 (23.3%) had an overlap syndrome of primary sclerosing cholangitis/autoimmune hepatitis. When PSC was detected before IBD (6/30–20%), patients had complications more often compared to those diagnosed with IBD first or PSC and IBD at the same time. At the moment of diagnosis 6/30 (20%) patients presented with abdominal pain, which was the most common symptom, 3/30 (10%) jaundice, while 17/30 (56.6%) were asymptomatic but had abnormal results of the laboratory tests. Conclusions: Monitoring liver markers in IBD patients is important since most PSC cases are asymptomatic and their elevation might be the first sign of the disease. Patients diagnosed with PSC before IBD diagnosis are more likely to have a more aggressive course of the disease.
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Affiliation(s)
- Sabina Wiecek
- Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 16 Medykow Street, 40-752 Katowice, Poland
| | - Alicja Wojtyniak
- Student Scientific Club, Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | - Barbara Pindur
- Student Scientific Club, Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | | | - Katarzyna Gruszczyńska
- Department of Radiology and Nuclear Medicine, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
| | - Urszula Grzybowska-Chlebowczyk
- Department of Paediatrics, Faculty of Medical Sciences, Medical University of Silesia, 16 Medykow Street, 40-752 Katowice, Poland
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Truong SDA, Tummanatsakun D, Proungvitaya T, Limpaiboon T, Wongwattanakul M, Chua-on D, Roytrakul S, Proungvitaya S. Serum Levels of Cytokine-Induced Apoptosis Inhibitor 1 (CIAPIN1) as a Potential Prognostic Biomarker of Cholangiocarcinoma. Diagnostics (Basel) 2021; 11:diagnostics11061054. [PMID: 34201138 PMCID: PMC8227425 DOI: 10.3390/diagnostics11061054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 01/17/2023] Open
Abstract
The mortality rate of cholangiocarcinoma (CCA) is high since there is a lack of a non-invasive technique to accurately detect tumors at the early stage. CCA biomarkers are consistently needed for various purposes including screening, early diagnosis, prognosis and follow-up. Herein, using bioinformatic analysis of our mitochondrial proteome database of CCA tissues, we identified cytokine-induced apoptosis inhibitor 1 (CIAPIN1) as a potential prognostic biomarker for CCA. CIAPIN1 levels in the sera of 159 CCA patients and 93 healthy controls (HC) were measured using a dot blot assay. The median level ± quartile deviation of CIAPIN1 level in the sera of CCA patient group was 0.5144 ± 0.34 µg/µL, which was significantly higher than 0.2427 ± 0.09 µg/µL of the HC group (p < 0.0001). In CCA patients, higher serum CIAPIN1 level was significantly associated with lymph node metastasis (p = 0.024) and shorter overall survival time (p = 0.001, Kaplan–Meier test). Cox regression analysis showed that the serum CIAPIN1 level can be an independent prognostic indicator for the survival of CCA patients. Moreover, for the prediction of CCA prognosis, CIAPIN1 is superior to CEA, CA19-9 and ALP. In conclusion, CIAPIN1 can be a serum biomarker candidate for the poor prognosis of CCA.
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Affiliation(s)
- Son Dinh An Truong
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
| | - Doungdean Tummanatsakun
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
| | - Tanakorn Proungvitaya
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
| | - Temduang Limpaiboon
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
- Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Molin Wongwattanakul
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
- Center for Innovation and Standard for Medical Technology and Physical Therapy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Daraporn Chua-on
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
| | - Sittiruk Roytrakul
- National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani 12120, Thailand;
| | - Siriporn Proungvitaya
- Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; (S.D.A.T.); (D.T.); (T.P.); (T.L.); (M.W.); (D.C.-o.)
- Center for Innovation and Standard for Medical Technology and Physical Therapy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
- Correspondence: ; Tel.: +66-4-3202088
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Mao X, Wen F, Liang H, Sun W, Lu Z. A preliminary single-center investigation of percutaneous biliary stenting in malignant hilar biliary obstruction: what impacts the clinical success and the long-term outcomes? Support Care Cancer 2021; 29:6781-6792. [PMID: 33990879 DOI: 10.1007/s00520-021-06271-0] [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: 01/19/2021] [Accepted: 05/04/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE The purpose of this study is to investigate the influencing factors that may impact the clinical success, jaundice-free time, and overall survival in patients of malignant hilar biliary obstruction (MHBO) treated with a self-expanding metallic stent (SEMS). MATERIALS AND METHODS Patients diagnosed with MHBO and treated with SEMS through percutaneous access from 1 Jul. 2013 to 1 Jul. 2018 were enrolled in this monocentric study. Demographic information, disease baseline measurements, and interventional strategies were collected and examined. Bilirubin was measured 1-3 days before and 3-7 days after stenting using the unit of "μmol/L." The bilirubin reduction ratio was compared between different study groups, which were separated by specific characteristics. Univariate and multivariate analyses were performed to evaluate each characteristic's impact on jaundice-free time (JF) and overall survival time (OS). Statistical analyses were conducted using SPSS 14.0, p < 0.05 indicated significance. RESULTS Eighty patients were enrolled. Direct bilirubin (DB) and indirect bilirubin (IB) both significantly decreased after stenting (U = 1575.0, p < 0.001; U = 1541.0, p < 0.001). The DB reduction ratio of the "nearby lymph metastases" group was significantly higher (U = 566.0, p = 0.037). The IB reduction ratio in the "single stent" group was significantly higher (U = 554.0, p = 0.018). Sixty-six cases reached jaundice recurrence, the median JF was 6 months, and the 95% confidence interval was 4.411 ~ 7.589 months. Fifty-eight cases ended in death, the median OS was 7 months, and the 95% confidence interval was 5.759 ~ 8.241 months. "Nearby lymph metastases" and "distant metastases" independently impacted OS (OR = 2.344, p = 0.013; OR = 3.239, p = 0.042). "IB reduction ratio" independently impacted both JF and OS (OR = 0.422, p = 0.021; OR = 0.315, p = 0.001). CONCLUSION The goal of treatment in patients with MHBO is to recover liver function. However, the overall survival is greatly impacted by the presence of metastases. Managing to obtain adequate liver function recovery may improve the long-term outcomes in affected patients.
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Affiliation(s)
- Xiaonan Mao
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Feng Wen
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Hongyuan Liang
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Wei Sun
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China
| | - Zaiming Lu
- Department of Radiology, Shengjing Hospital of China Medical University, Huaxiang Road 39, Shenyang City, 110004, Liaoning Province, China.
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Lee T, Teng TZJ, Shelat VG. Carbohydrate antigen 19-9 - tumor marker: Past, present, and future. World J Gastrointest Surg 2020; 12:468-490. [PMID: 33437400 PMCID: PMC7769746 DOI: 10.4240/wjgs.v12.i12.468] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/06/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a cell surface glycoprotein complex most commonly associated with pancreatic ductal adenocarcinoma (PDAC). Koprowski first described it in 1979 using a mouse monoclonal antibody in a colorectal carcinoma cell line. Historically, it is one of the most commonly used tumor markers for diagnosing, managing, and prognosticating PDAC. Additionally, elevated CA 19-9 levels are used as an indication for surgery in suspected benign pancreatic conditions. Another common application of CA 19-9 in the biliary tract includes its use as an adjunct in diagnosing cholangiocarcinoma. However, its clinical value is not limited to the hepatopancreatobiliary system. The reality is that the advancing literature has broadened the clinical value of CA 19-9. The potential value of CA 19-9 in patients' workup extends its reach to gastrointestinal cancers - such as colorectal and oesophageal cancer - and further beyond the gastrointestinal tract - including urological, gynecological, pulmonary, and thyroid pathologies. Apart from its role in investigations, CA 19-9 presents a potential therapeutic target in PDAC and acute pancreatitis. In a bid to consolidate its broad utility, we appraised and reviewed the biomarker's current utility and limitations in investigations and management, while discussing the potential applications for CA 19-9 in the works for the future.
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Affiliation(s)
- Tsinrong Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Thomas Zheng Jie Teng
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Vishal G Shelat
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Driescher C, Fuchs K, Haeberle L, Goering W, Frohn L, Opitz FV, Haeussinger D, Knoefel WT, Keitel V, Esposito I. Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer. Cancers (Basel) 2020; 13:E39. [PMID: 33375555 PMCID: PMC7818177 DOI: 10.3390/cancers13010039] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/16/2020] [Accepted: 12/22/2020] [Indexed: 12/13/2022] Open
Abstract
Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma. Blood (n = 37) and bile (n = 21) samples were collected from patients affected by pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (CCA) or with non-malignant biliary obstructions (blood n = 16; bile n = 21). Panel-based next generation sequencing (NGS) and digital droplet PCR (ddPCR) were applied for tumor mutation profiling. NGS results from matched tumor tissues (n = 29) served as comparison. Sequencing of cfDNA from bile resulted in detection of 96.2% of the pathogenic tumor mutations found in matched tissue samples. On the other hand, only 31.6% of pathogenic tumor mutations found in tissue could be detected in plasma. In a direct comparison, only half of the mutations detected in bile cfDNA were concordantly detected in plasma from the same patients. Panel NGS and ddPCR displayed comparable sensitivity. In conclusion, bile is a suitable source of cfDNA for the diagnosis of pancreatobiliary cancer and performs more reliably than plasma. Although primary diagnosis still requires histologic confirmation, bile-derived cfDNA could offer an alternative if tissue sampling is not feasible and might allow less invasive disease monitoring.
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Affiliation(s)
- Caroline Driescher
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
| | - Katharina Fuchs
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (K.F.); (D.H.); (V.K.)
| | - Lena Haeberle
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
| | - Wolfgang Goering
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
| | - Lisa Frohn
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
| | - Friederike V. Opitz
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
| | - Dieter Haeussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (K.F.); (D.H.); (V.K.)
| | - Wolfram Trudo Knoefel
- Department of General, Thoracic and Pediatric Surgery, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany;
| | - Verena Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (K.F.); (D.H.); (V.K.)
| | - Irene Esposito
- Institute of Pathology, Heinrich-Heine-University and University Hospital of Duesseldorf, 40225 Duesseldorf, Germany; (C.D.); (L.H.); (W.G.); (L.F.); (F.V.O.)
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Kong J, Shen S, Zhang Z, Wang W. Identification of hub genes and pathways in cholangiocarcinoma by coexpression analysis. Cancer Biomark 2020; 27:505-517. [PMID: 32116234 DOI: 10.3233/cbm-190038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is the most common biliary malignancy worldwide. However, the molecular mechanisms of its tumorigenesis and progression are still largely unclear. OBJECTIVE This study aimed to explore the hub genes and pathways associated with CCA prognosis by coexpression analysis. METHODS A coexpression network complex was constructed using the top 20% most variant genes in the GSE89748 dataset to find modules associated with prognosis related clinical trait-histology. The hub genes in the clinically significant modules were defined as candidates if they were common in both the coexpression network and protein-protein interaction (PPI) network. Afterwards, survival analysis, expression level analysis and a series of bioinformatic analysis were used to validate the hub genes. RESULTS Twenty-five modules were obtained, and the cyan, light cyan and red modules regarded as closely associated with histology were selected. Subsequently, combining the PPI network complexes and coexpression networks, we screened 20 candidates. After expression and survival analysis, 10 real hub genes (LIMA1, HDAC1, ITGA3, ACTR3, GSK3B, ITGA2, THOC2, PTGES3, HEATR1 and ILF2) were finally identified. Additionally, functional enrichment analysis revealed that the hub genes were mainly enriched in cell cycle-related pathways. CONCLUSIONS Overall, this study identified 10 hub genes and cell cycle-related pathways were closely related to CCA development, progression and prognosis, which may contribute to CCA diagnosis and treatment.
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Luang S, Teeravirote K, Saentaweesuk W, Ma-In P, Silsirivanit A. Carbohydrate Antigen 50: Values for Diagnosis and Prognostic Prediction of Intrahepatic Cholangiocarcinoma. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:616. [PMID: 33207685 PMCID: PMC7696328 DOI: 10.3390/medicina56110616] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023]
Abstract
Background and objectives: Cancer-associated carbohydrate antigen 50 (CA50) is a marker for detection of gastrointestinal cancers, especially of pancreatic and colon cancer. In this study, the power of CA50 as a diagnostic and prognostic marker was evaluated in intrahepatic cholangiocarcinoma (iCCA). Materials and Methods: Serum CA50 levels of iCCA patients and non-cholangiocarcinoma controls (non-CCA, including healthy persons and patients with benign biliary diseases and other gastrointestinal cancers) were measured using MAGLUMI®800 CLIA analyzer. Diagnostic and prognostic values of serum CA50 levels were evaluated. Results: CA50 levels in the sera of iCCA patients were significantly higher than those of non-CCA controls (p < 0.001, Mann-Whitney U test). Using cut-off value of 25 U/mL, CA50 provided 65.9% sensitivity, 87.3% specificity, and 80.1% accuracy for diagnosis of iCCA. Serum CA50 levels were increased and associated with the severity of bile duct pathology. In addition, a higher level of CA50 was associated with poor clinical outcome and shorter survival in iCCA patients. Multivariate survival analysis by Cox regression model revealed the potential of CA50 as an independent poor prognostic indicator for iCCA, regardless of the age, sex, histological types, or tumor stages. Conclusions: CA50 can be a diagnostic and poor prognostic marker candidate for iCCA.
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Affiliation(s)
- Sukanya Luang
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.L.); (K.T.); (P.M.-I.)
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Karuntarat Teeravirote
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.L.); (K.T.); (P.M.-I.)
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
| | | | - Prasertsri Ma-In
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.L.); (K.T.); (P.M.-I.)
| | - Atit Silsirivanit
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; (S.L.); (K.T.); (P.M.-I.)
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
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Salem PES, Ghazala RA, El Gendi AM, Emara DM, Ahmed NM. The association between circulating MicroRNA-150 level and cholangiocarcinoma. J Clin Lab Anal 2020; 34:e23397. [PMID: 33161598 PMCID: PMC7676191 DOI: 10.1002/jcla.23397] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/06/2019] [Accepted: 11/24/2019] [Indexed: 12/17/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a rare tumor which requires a multimodality approach for its diagnosis. Carbohydrate antigen 19‐9 (CA19‐9) is currently the most commonly used tumor marker for CCA; nevertheless, it has certain limitations which need to be considered when using it as a tumor marker. MiRNA‐150 altered expression has been linked to the development and tumorigenesis of several cancers including CCA. This work aimed to study the serum level of CA19‐9 and miRNA‐150 expression in CCA patients and, also, to correlate their levels with tumor staging and different studied clinical and laboratory parameters. This work included 35 patients with CCA who were admitted to Hepatobiliary Unit, Alexandria Main University Hospital (Group I). Also, 35 age‐ and sex‐matched healthy subjects were included as a control group (Group II). All included subjects were submitted to measurement of serum CA19‐9 and MiRNA‐150 expression levels. Serum CA19‐9 levels showed an evident high median among CCA patients, while serum miRNA‐150 expression levels were evidently low among those patients. Moreover, combining miRNA‐150 with CA19‐9 made the accuracy of diagnosis of CCA much more reliable. Thus, miRNA‐150 can be considered as a non‐invasive, sensitive serum biomarker for the diagnosis of CCA especially when combined with CA 19‐9.
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Affiliation(s)
- Perihan El Sayed Salem
- Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | | | | | - Doaa Mokhtar Emara
- Department of Radiodiagnosis and Intervention Radiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Nesma Mahmoud Ahmed
- Internal Medicine Department, Fever Hospital, Alexandria University, Alexandria, Egypt
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Song J, Li Y, Bowlus CL, Yang G, Leung PSC, Gershwin ME. Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis (PSC): a Comprehensive Review. Clin Rev Allergy Immunol 2020; 58:134-149. [PMID: 31463807 DOI: 10.1007/s12016-019-08764-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC) and carries a high rate of mortality. Although the pathogenesis of CCA in PSC is largely unknown, inflammation-driven carcinogenesis concomitant with various genetic and epigenetic abnormalities are underlying factors. The majority of CCA cases develop from a dominant stricture (DS), which is defined as a stricture with a diameter < 1.5 mm in the common bile duct or < 1.0 mm in the hepatic duct. In PSC patients presenting with an abrupt aggravation of jaundice, pain, fatigue, pruritus, weight loss, or worsening liver biochemistries, CCA should be suspected and evaluated utilizing a variety of diagnostic modalities. However, early recognition of CCA in PSC remains a major challenge. Importantly, 30-50% of CCA in PSC patients are observed within the first year following the diagnosis of PSC followed by an annual incidence ranging from 0.5 to 1.5 per 100 persons, which is nearly 10 to 1000 times higher than that in the general population. Cumulative 5-year, 10-year, and lifetime incidences are 7%, 8-11%, and 9-20%, respectively. When PSC-associated CCA is diagnosed, most tumors are unresectable, and no effective medications are available. Given the poor therapeutic outcome, the surveillance and management of PSC patients who are at an increased risk of developing CCA are of importance. Such patients include older males with large-duct PSC and possibly concurrent ulcerative colitis. Thus, more attention should be paid to patients with these clinical features, in particular within the first year after PSC diagnosis. In contrast, CCA is less frequently observed in pediatric or female PSC patients or in those with small-duct PSC or concurrent Crohn's disease. Recently, new biomarkers such as antibodies to glycoprotein 2 have been found to be associated with an increased risk of developing CCA in PSC. Herein, we review the literature on the pathogenesis, incidence, clinical features, and risk factors, with a focus on various diagnostic modalities of PSC-associated CCA.
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Affiliation(s)
- Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.,Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Yang Li
- Department of Intensive Care Unit (ICU), Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People's Republic of China
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA
| | - GuoXiang Yang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA
| | - Patrick S C Leung
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, 451 Health Science Drive, Suite 6510, Davis, CA, 95616, USA.
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Rizzo A, Ricci AD, Tavolari S, Brandi G. Circulating Tumor DNA in Biliary Tract Cancer: Current Evidence and Future Perspectives. Cancer Genomics Proteomics 2020; 17:441-452. [PMID: 32859625 PMCID: PMC7472453 DOI: 10.21873/cgp.20203] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/19/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Peripheral blood of cancer patients "physiologically" presents cells and cellular components deriving from primary or metastatic sites, including circulating tumor cells (CTCs), circulating free DNA (cfDNA) and exosomes containing proteins, lipids and nucleic acids. The term circulating tumor DNA (ctDNA) indicates the part of cfDNA which derives from primary tumors and/or metastatic sites, carrying tumor-specific genetic or epigenetic alterations. Analysis of ctDNA has enormous potential applications in all stages of cancer management, including earlier diagnosis of cancer, identification of driver alterations, monitoring of treatment response and detection of resistance mechanisms. Thus, ctDNA has the potential to profoundly change current clinical practice, by moving from tissue to peripheral blood as a source of information. Herein, we review current literature regarding the potential role for ctDNA in biliary tract cancer (BTC) patients, with a particular focus on state-of-the-art techniques and future perspectives of this highly aggressive disease.
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Affiliation(s)
- Alessandro Rizzo
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Angela Dalia Ricci
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Simona Tavolari
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, Bologna, Italy
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Vedeld HM, Folseraas T, Lind GE. Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis - The promise of DNA methylation and molecular biomarkers. JHEP Rep 2020; 2:100143. [PMID: 32939446 PMCID: PMC7479288 DOI: 10.1016/j.jhepr.2020.100143] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/25/2020] [Accepted: 06/30/2020] [Indexed: 02/07/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a highly fatal malignancy of the bile ducts that arises in up to 20% of patients with primary sclerosing cholangitis (PSC). Current detection methods for CCA display suboptimal sensitivity and/or specificity, and there is no evidence-based screening strategy for CCA in patients with PSC. Consequently, CCA is often detected too late for surgical resection, contributing to the high mortality associated with this malignancy. Recently, biomarkers have emerged with potential to complement current detection methods, and/or be used for cancer surveillance in high-risk patient groups, including patients with PSC. Aberrant DNA methylation patterns represent promising biomarkers with great potential for CCA detection. Such aberrations are frequent in CCA, often occur early, and can be detected in liquid biopsies, including blood, bile and urine. This review summarises and highlights the most promising DNA methylation biomarkers identified for CCA detection so far, focusing on patients with PSC. Other promising molecular biomarkers for detection of PSC-associated CCA in liquid biopsies will also be briefly covered.
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Affiliation(s)
- Hege Marie Vedeld
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.,K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway
| | - Trine Folseraas
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.,Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Guro Elisabeth Lind
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.,K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway
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50
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Zacarias MS, Pria HRFD, de Oliveira RAS, Delmonte LF, Velloni FG, D'Ippolito G. Non-neoplastic cholangiopathies: an algorithmic approach. Radiol Bras 2020; 53:262-272. [PMID: 32904723 PMCID: PMC7458557 DOI: 10.1590/0100-3984.2019.0069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cholangiopathies are chronic diseases that affect the bile ducts, comprising a heterogeneous group of progressive and potentially fatal entities. The diagnosis of these diseases is a great challenge for radiologists because of the overlapping of their clinical, biochemical, and imaging findings. Nevertheless, identifying the precise etiology is crucial, given that the therapeutic options are distinct and influence the prognosis of the patient. The purpose of this review article is to discuss some of the non-neoplastic causes of cholangiopathies and to provide a useful diagnostic algorithm.
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Affiliation(s)
- Marina Silva Zacarias
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Hanna Rafaela Ferreira Dalla Pria
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Rafael Andrade Santiago de Oliveira
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Luis Fernando Delmonte
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Fernanda Garozzo Velloni
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
| | - Giuseppe D'Ippolito
- Departamento de Diagnóstico por Imagem - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), São Paulo, SP, Brazil
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