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Lee J, Jeong S, Lee DH, Choi SJ, Shin WY. Diagnostic Challenges in Follicular Cholangitis Mimicking Hilar Cholangiocarcinoma: A Case Report and Review of the Literature. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1513. [PMID: 39336554 PMCID: PMC11433704 DOI: 10.3390/medicina60091513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024]
Abstract
Introduction: Distinguishing benign from malignant biliary strictures remains challenging despite diagnostic advancements. Follicular cholangitis, a rare benign condition, presents with symptoms and imaging similar to malignancies like cholangiocarcinoma, often complicating diagnosis, particularly when tumor markers are elevated and imaging suggests metastasis. Case presentation: A 57-year-old woman with hypertension and diabetes was admitted with jaundice. Elevated bilirubin and liver enzymes alongside high carbohydrate antigen 19-9 (CA19-9) levels but normal carcinoembryonic antigen (CEA) were noted. Imaging showed thickening from the hilar duct to the proximal common bile duct, accompanied by suspected lymph node metastases. Comprehensive ERCP-guided biopsies found no malignancy. Surgical resection led to a diagnosis of follicular cholangitis. Conclusions: Follicular cholangitis' long-term prognosis is elusive due to its rarity, and preoperative diagnosis is challenging. Increased awareness may improve diagnostic and treatment approaches, as this case adds to the disease's understanding.
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Affiliation(s)
- Jungnam Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
| | - Don Haeng Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
| | - Suk Jin Choi
- Department of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
| | - Woo Young Shin
- Department of Surgery, Inha University Hospital, Inha University School of Medicine, Incheon 22332, Republic of Korea
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Kubota K, Iwasaki E, Ishikawa T, Kuwatani M, Takenaka M, Iwashita T, Masuda A, Ikeura T, Nakamura A, Tanaka A, Isayama H, Hirooka Y, Hirano K, Ryozawa S, Ogura T, Fujisawa T, Kurita Y, Kikuta K, Hayashi N, Masamune A, Yasuda I. Diagnosis of isolated hilar-/extrahepatic-type IgG-4-related sclerosing cholangitis can be increased by improved recognition of this condition-A Japanese multicenter analysis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:647-657. [PMID: 39123289 DOI: 10.1002/jhbp.12053] [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: 08/12/2024]
Abstract
BACKGROUND Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population. METHODS This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC. RESULTS Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria. CONCLUSION Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial.
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Affiliation(s)
| | - Eisuke Iwasaki
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, Keio University, Minato, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Nagoya University, Nagoya, Japan
| | - Masaki Kuwatani
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kindai University Faculty of Medicine, Higashiosaka, Japan
| | - Takuji Iwashita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tsukasa Ikeura
- The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Akira Nakamura
- Department of Gastroenterology, Shinshu University, Matsumoto, Japan
| | | | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Bunkyo, Japan
| | - Yoshiki Hirooka
- Gastroenterology and Hepatology, Fujita Health University, Toyoake, Japan
| | - Kenji Hirano
- Department of Gastroenterology, Tokyo Takanawa Hospital, Minato, Japan
| | - Shomei Ryozawa
- Department of Gastroenterology, Saitama Medical University International Medical Center, Hidaka, Japan
| | - Takeshi Ogura
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan
| | - Toshio Fujisawa
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Bunkyo, Japan
| | - Yusuke Kurita
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kazuhiro Kikuta
- Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Nobuhiko Hayashi
- Third Department of Internal Medicine, Graduate School of Medicine, University of Toyama, Toyama, Japan
| | - Atsushi Masamune
- Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ichiro Yasuda
- Third Department of Internal Medicine, Graduate School of Medicine, University of Toyama, Toyama, Japan
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Miller LJ, Holmes IM, Chen-Yost HI, Smola B, Lew M, Betz BL, Brown NA, Pang J. Performance of fluorescence in situ hybridization in biliary brushings with equivocal cytology: an institutional experience. J Am Soc Cytopathol 2024; 13:285-290. [PMID: 38589274 DOI: 10.1016/j.jasc.2024.03.002] [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: 12/15/2023] [Revised: 03/12/2024] [Accepted: 03/12/2024] [Indexed: 04/10/2024]
Abstract
INTRODUCTION Biliary brushing (BB) cytology has a sensitivity of 15%-65% and specificity approaching 100% for detecting malignancy. Fluorescence in-situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of malignancies with reported sensitivity of 43%-84%. We sought to evaluate the performance of FISH in BB with equivocal cytology at our institution. MATERIALS AND METHODS Patients with atypical and suspicious BB with concurrent diagnostic FISH performed at our institution from 2014 to 2021 were identified through a query of our pathology database. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed for pathology results and outcomes. Patients were classified malignant if they had positive pathology or documented clinical impression of malignancy and benign if they had negative pathology and/or documented benign clinical course for at least 12 months. RESULTS We identified 254 equivocal BB (238 atypical/16 suspicious) with concurrent FISH results from 191 patients (105 benign, 86 malignant). 12% (22/191) of patients were FISH positive. Twenty-four percent (21/86) of patients with malignancy had positive FISH but were nonspecific for pancreaticobiliary/ampullary adenocarcinomas. Almost all positive FISH were associated with malignancy (21/22; 95%). There was 1 positive FISH in a patient with primary sclerosing cholangitis who had a benign outcome. CONCLUSIONS The small number of positive FISH results in BB with equivocal cytology raises the question of the optimal criteria for malignancy. Using only polysomy could result in lower sensitivity.
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Affiliation(s)
- Lauren J Miller
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
| | | | | | - Brian Smola
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
| | - Madelyn Lew
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
| | - Bryan L Betz
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
| | - Noah A Brown
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan
| | - Judy Pang
- Department of Pathology, Michigan Medicine, Ann Arbor, Michigan.
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Affarah L, Berry P, Kotha S. Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures. World J Gastrointest Endosc 2024; 16:297-304. [PMID: 38946851 PMCID: PMC11212512 DOI: 10.4253/wjge.v16.i6.297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/09/2024] [Accepted: 05/07/2024] [Indexed: 06/13/2024] Open
Abstract
Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists. Despite advances in endoscopic techniques and instruments, it is difficult to differentiate between benign and malignant pathology. A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery, or to inform other types of therapy. Endoscopic retrograde cholangiopancreatography with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate. Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality. In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate histology to facilitate clinical management.
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Affiliation(s)
- Lynn Affarah
- Department of Hepatology, Guy's and St Thomas' Hospital, London SE1 7EH, United Kingdom
| | - Philip Berry
- Department of Hepatology, Guy's and St Thomas' Hospital, London SE1 7EH, United Kingdom
| | - Sreelakshmi Kotha
- Department of Hepatology, Guy's and St Thomas' Hospital, London SE1 7EH, United Kingdom
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Kim HS, Kang MJ, Kang J, Kim K, Kim B, Kim SH, Kim SJ, Kim YI, Kim JY, Kim JS, Kim H, Kim HJ, Nahm JH, Park WS, Park E, Park JK, Park JM, Song BJ, Shin YC, Ahn KS, Woo SM, Yu JI, Yoo C, Lee K, Lee DH, Lee MA, Lee SE, Lee IJ, Lee H, Im JH, Jang KT, Jang HY, Jun SY, Chon HJ, Jung MK, Chung YE, Chong JU, Cho E, Chie EK, Choi SB, Choi SY, Choi SJ, Choi JY, Choi HJ, Hong SM, Hong JH, Hong TH, Hwang SH, Hwang IG, Park JS. Practice guidelines for managing extrahepatic biliary tract cancers. Ann Hepatobiliary Pancreat Surg 2024; 28:161-202. [PMID: 38679456 PMCID: PMC11128785 DOI: 10.14701/ahbps.23-170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 02/14/2024] [Accepted: 02/15/2024] [Indexed: 05/01/2024] Open
Abstract
Backgrounds/Aims Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
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Affiliation(s)
- Hyung Sun Kim
- Department of Surgery, Pancreatobiliary Clinic, Yonsei University College of Medicine, Seoul, Korea
| | - Mee Joo Kang
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Jingu Kang
- Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul, Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Bohyun Kim
- Department of Radiology, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea
| | - Seong-Hun Kim
- Department of Internal Medicine, Jeonbuk National University Medical School and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Soo Jin Kim
- Department of Radiology, National Cancer Center, Goyang, Korea
| | - Yong-Il Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Young Kim
- Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Jin Sil Kim
- Department of Radiology, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo Jung Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Ji Hae Nahm
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Suk Park
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary’s Hospital College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Eunkyu Park
- Division of HBP Surgery, Department of Surgery, Chonnam National University Hospital, Gwangju, Korea
| | - Joo Kyung Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Myung Park
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Byeong Jun Song
- Department of Internal Medicine, Myongji Hospital, Goyang, Korea
| | - Yong Chan Shin
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Keun Soo Ahn
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Hospital, Daegu, Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, Hospital, Immuno-Oncology Branch Division of Rare and Refractory Center, Research Institute of National Cancer Center, Goyang, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoungbun Lee
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Eun Lee
- Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Ik Jae Lee
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Huisong Lee
- Department of Surgery, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Jung Ho Im
- Department of Radiation Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hye Young Jang
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun-Young Jun
- Department of Pathology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hong Jae Chon
- Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Min Kyu Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Yong Eun Chung
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Uk Chong
- Department of Surgery, National Health Insurance Services Ilsan Hospital, Goyang, Korea
| | - Eunae Cho
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Sae Byeol Choi
- Department of Surgery, Korea Universtiy Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Seo-Yeon Choi
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Ji Choi
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hye-Jeong Choi
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Hyung Hong
- Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Ho Hong
- Division of Hepato-Biliary and Pancreas Surgery, Department of Surgery, Seoul St. Mary’s Hospital College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Shin Hye Hwang
- Department of Radiology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - In Gyu Hwang
- Division of Hemato-Oncology, Department of Internal Medicine, Chung-Ang University Hospital Chung-Ang University College of Medicine, Seoul, Korea
| | - Joon Seong Park
- Department of Surgery, Pancreatobiliary Clinic, Yonsei University College of Medicine, Seoul, Korea
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Pallio S, Sinagra E, Santagati A, D'Amore F, Pompei G, Conoscenti G, Romeo F, Borina E, Melita G, Rossi F, Maida M, Alloro R, Tarantino I, Raimondo D. Use of catheter-based cholangioscopy in the diagnosis of indeterminate stenosis: a multicenter experience. Minerva Gastroenterol (Torino) 2024; 70:29-35. [PMID: 35262304 DOI: 10.23736/s2724-5985.22.02889-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Direct bile ducts visualization through cholangioscopy has gained popularity due to its better diagnostic accuracy than a standard ERCP in indeterminate biliary stricture. METHODS We aimed to review our catheter-based cholangioscopy interventions in patients with indeterminate biliary stenosis, using the SpyGlass Direct Visualization System (SDVS) and summarize our experience in terms of procedures and results. We collected 25 consecutive patients with indeterminate biliary stricture over 3 years. RESULTS The overall procedural success in our cohort amounted to 96% (24/25). If we focus on the diagnostic procedures, the ability to merely visualize the region of interest/lesion and perform biopsy of the lesion was possible in 96% (24/25) In our cohort localization in the common bile duct (P=0.03; 95% CI: 0.27-0.96) was found as positive determining factor for diagnosis. Sensitivity, specificity and accuracy for visual diagnosis by SDVS in our cohort were 100, 83.3 and 96%, respectively. The use of biopsy or obtaining a histological diagnosis to assist in identifying patients with malignant stenosis, to exclude malignancy and to correctly classify diagnosed patients resulted in a sensitivity of 100%, a specificity of 73% with an overall accuracy of 94.4%. Only a mild adverse event (cholangitis, treated conservatively) occurred. CONCLUSIONS Today, the SDVS should be considered essential in diagnosing indeterminate biliary strictures, since the procedure is associated with high procedural success in terms of diagnostic accuracy, alters clinical outcome in over 80% of considered insolvable cases, with an acceptable safety profile.
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Affiliation(s)
- Socrate Pallio
- Unit of Endoscopy, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Emanuele Sinagra
- Unit of Endoscopy, G. Giglio Institute Foundation, Cefalù, Palermo, Italy -
- Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
| | | | - Fabio D'Amore
- Unit of Endoscopy, San Vincenzo Hospital, Taormina, Messina, Italy
| | - Giancarlo Pompei
- Unit of Pathology, G. Giglio Institute Foundation, Cefalù, Palermo, Italy
| | | | - Fabio Romeo
- Unit of Endoscopy, San Vincenzo Hospital, Taormina, Messina, Italy
| | - Eleonora Borina
- Unit of Endoscopy, San Vincenzo Hospital, Taormina, Messina, Italy
| | - Giuseppinella Melita
- Unit of Endoscopy, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Francesca Rossi
- Unit of Endoscopy, G. Giglio Institute Foundation, Cefalù, Palermo, Italy
| | - Marcello Maida
- Unit of Gastroenterology and Endoscopy, S. Elia-Raimondi Hospital, Caltanissetta, Italy
| | - Rita Alloro
- Emergency Unit, G. Giglio Institute Foundation, Cefalù, Palermo, Italy
| | - Ilaria Tarantino
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Dario Raimondo
- Unit of Endoscopy, G. Giglio Institute Foundation, Cefalù, Palermo, Italy
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7
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Fujii-Lau LL, Thosani NC, Al-Haddad M, Acoba J, Wray CJ, Zvavanjanja R, Amateau SK, Buxbaum JL, Wani S, Calderwood AH, Chalhoub JM, Coelho-Prabhu N, Desai M, Elhanafi SE, Fishman DS, Forbes N, Jamil LH, Jue TL, Kohli DR, Kwon RS, Law JK, Lee JK, Machicado JD, Marya NB, Pawa S, Ruan W, Sawhney MS, Sheth SG, Storm A, Thiruvengadam NR, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: methodology and review of evidence. Gastrointest Endosc 2023; 98:694-712.e8. [PMID: 37307901 DOI: 10.1016/j.gie.2023.06.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/14/2023]
Abstract
Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsy sampling, brush cytology, cholangioscopy, and EUS-guided FNA or fine-needle biopsy sampling, the American Society for Gastrointestinal Endoscopy Standards of Practice Committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, whereas the accompanying article subtitled "Summary and Recommendations" contains a concise summary of our findings and final recommendations.
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Affiliation(s)
| | | | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Jared Acoba
- Department of Hematology and Medical Oncology, University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | | | - Rodrick Zvavanjanja
- Department of Diagnostic and Interventional Imaging, UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Stuart K Amateau
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Jean M Chalhoub
- Department of Gastroenterology and Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
| | | | - Madhav Desai
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Sherif E Elhanafi
- Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas, USA
| | - Douglas S Fishman
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Nauzer Forbes
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Laith H Jamil
- Section of Gastroenterology and Hepatology, Beaumont Health, Royal Oak, and Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
| | - Terry L Jue
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Divyanshoo R Kohli
- Pancreas and Liver Clinic, Providence Sacred Heart Medical Center, Spokane, Washington, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Joanna K Law
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA
| | - Jorge D Machicado
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Neil B Marya
- Division of Gastroenterology and Hepatology, UMass Chan Medical School, Worcester, Massachusetts, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Wenly Ruan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University, Loma Linda, California, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures. Am J Gastroenterol 2023; 118:405-426. [PMID: 36863037 DOI: 10.14309/ajg.0000000000002190] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/13/2022] [Indexed: 03/04/2023]
Abstract
A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver that can result in clinically and physiologically relevant obstruction to the flow of bile. The most common and ominous etiology is malignancy, underscoring the importance of a high index of suspicion in the evaluation of this condition. The goals of care in patients with a biliary stricture are confirming or excluding malignancy (diagnosis) and reestablishing flow of bile to the duodenum (drainage); the approach to diagnosis and drainage varies according to anatomic location (extrahepatic vs perihilar). For extrahepatic strictures, endoscopic ultrasound-guided tissue acquisition is highly accurate and has become the diagnostic mainstay. In contrast, the diagnosis of perihilar strictures remains a challenge. Similarly, the drainage of extrahepatic strictures tends to be more straightforward and safer and less controversial than that of perihilar strictures. Recent evidence has provided some clarity in multiple important areas pertaining to biliary strictures, whereas several remaining controversies require additional research. The goal of this guideline is to provide practicing clinicians with the most evidence-based guidance on the approach to patients with extrahepatic and perihilar strictures, focusing on diagnosis and drainage.
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9
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Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video). Gastrointest Endosc 2023; 97:268-278.e1. [PMID: 36007584 DOI: 10.1016/j.gie.2022.08.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/04/2022] [Accepted: 08/13/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND AND AIMS Accurately diagnosing malignant biliary strictures (MBSs) as benign or malignant remains challenging. It has been suggested that direct visualization and interpretation of cholangioscopy images provide greater accuracy for stricture classification than current sampling techniques (ie, brush cytology and forceps biopsy sampling) using ERCP. We aimed to develop a convolutional neural network (CNN) model capable of accurate stricture classification and real-time evaluation based solely on cholangioscopy image analysis. METHODS Consecutive patients with cholangioscopy examinations from 2012 to 2021 were reviewed. A CNN was developed and tested using cholangioscopy images with direct expert annotations. The CNN was then applied to a multicenter, reserved test set of cholangioscopy videos. CNN performance was then directly compared with that of ERCP sampling techniques. Occlusion block heatmap analyses were used to evaluate and rank cholangioscopy features associated with MBSs. RESULTS One hundred fifty-four patients with available cholangioscopy examinations were included in the study. The final image database comprised 2,388,439 still images. The CNN demonstrated good performance when tasked with mimicking expert annotations of high-quality malignant images (area under the receiver-operating characteristic curve, .941). Overall accuracy of CNN-based video analysis (.906) was significantly greater than that of brush cytology (.625, P = .04) or forceps biopsy sampling (.609, P = .03). Occlusion block heatmap analysis demonstrated that the most frequent image feature for an MBS was the presence of frond-like mucosa/papillary projections. CONCLUSIONS This study demonstrates that a CNN developed using cholangioscopy data alone has greater accuracy for biliary stricture classification than traditional ERCP-based sampling techniques.
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10
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El Bacha H, Harizi R, Laugier R, Lorenzo D, Rivallin P, Leblanc S, Barange K, Fumex F, Laquière A, Napoléon B, Vedrenne B, Grabar S, Prat F. Identification of endoscopic predictors of biliary malignancy during digital cholangioscopy. Dig Endosc 2022; 34:1224-1233. [PMID: 35138664 DOI: 10.1111/den.14259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 01/26/2022] [Accepted: 01/30/2022] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Biliary brushings and biopsies obtained during endoscopic retrograde cholangiopancreatography (ERCP) have a low sensitivity for the diagnosis of malignant biliary strictures. While cholangioscopic analysis is useful, visual criteria have not yet been defined. The aim of this study was to identify visual criteria for the diagnosis of indeterminate biliary strictures (IDBS). METHODS A multicenter study was conducted based on the analysis of cholangioscopic recordings of IBDS. Diagnostic criteria were identified in a study group and verified in a validation group. RESULTS Four criteria were identified to be associated with malignancy, one negatively ("endobiliary material," odds ratio [OR] 0.62, 95% confidence interval [CI] 0.41-0.92) and three positively ("vascularized villous projections," OR 1.52, 95% CI 1.03-2.24; "twisted or dilated vessels," OR 2.18, 95% CI 1.47-3.24; and "dark color of the mucosa," OR 1.82, 95% CI 1.23-2.70). Between two playbacks, the mean (95% CI) sensitivity of the observer's visual diagnosis increased from 66.1% (60-72) to 73.8% (69-78) (P = 0.004); in the second playback, the kappa value for interobserver agreement ranged between 0.36 (color) and 0.56 (endobiliary material), with a significant improvement (P = 0.0031-0.0001) between the first and second playbacks. Blind assessment by endoscopists not involved in this study had a diagnostic accuracy of 73% (71.4-74.5). CONCLUSION The four identified cholangioscopic features are easy to implement in clinical practice and have the potential to increase the level of diagnostic confidence during the workup of IDBS.
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Affiliation(s)
- Hicham El Bacha
- Gastroenterology and Endoscopy Unit Medicine B, Mohammed V University in Rabat, Ibn Sina University Hospital, Rabat, Morocco
| | - Rafik Harizi
- Department of Biostatistics and Epidemiology, Cochin-Hôtel Dieu, University Hospitals of Paris (AP-HP), Paris, France
| | - René Laugier
- Gastroenterology and Endoscopy Unit, La Timone University Hospital, Marseilles, France
| | - Diane Lorenzo
- Endoscopy Unit, Beaujon Hospital, University Hospitals of Paris (AP-HP) and University of Paris, Clichy, France
| | - Paul Rivallin
- Endoscopy Unit, Beaujon Hospital, University Hospitals of Paris (AP-HP) and University of Paris, Clichy, France
| | - Sarah Leblanc
- Digestive Endoscopy Unit, Jean Mermoz Clinic, Lyon, France
| | - Karl Barange
- Gastroenterology and Endoscopy Unit, Toulouse University Hospital, Toulouse, France
| | - Fabien Fumex
- Digestive Endoscopy Unit, Jean Mermoz Clinic, Lyon, France
| | - Arthur Laquière
- Gastroenterology and Endoscopy Unit, Saint Joseph Hospital, Marseilles, France
| | | | - Bruno Vedrenne
- Gastroenterology and Endoscopy Unit, Mulhouse and Southern Alsace Regional Hospital, Mulhouse, France
| | - Sophie Grabar
- Department of Biostatistics and Epidemiology, Cochin-Hôtel Dieu, University Hospitals of Paris (AP-HP), Paris, France
| | - Frederic Prat
- Endoscopy Unit, Beaujon Hospital, University Hospitals of Paris (AP-HP) and University of Paris, Clichy, France
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11
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Kim SY, Moon SH, Cho YA, Lee SM, Kim JH. [Portal Biliopathy Misdiagnosed as Hilar Cholangiocarcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:38-42. [PMID: 35879062 DOI: 10.4166/kjg.2022.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 06/15/2023]
Abstract
Portal biliopathy refers to the changes in the bile duct caused by portal vein thrombosis or obstruction. It is assumed to be caused by cavernous transformation due to the development of the venous system surrounding the bile duct, but the exact pathology is still unknown. Biliary morphologic abnormalities of portal biliopathy are discovered incidentally on radiographic images, but it is sometimes difficult to differentiate them from cholangiocarcinoma. Given the poor prognosis of cholangiocarcinoma, a surgical approach can be considered when the diagnosis is uncertain. Herein, we report a case of portal biliopathy with bile ductal wall thickening, which was diagnosed after surgical resection was performed due to the presumed diagnosis of cholangiocarcinoma.
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Affiliation(s)
- Sung-Yeun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Yoon Ah Cho
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Sang Min Lee
- Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jong-Hyeok Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
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12
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Arechederra M, Rullán M, Amat I, Oyon D, Zabalza L, Elizalde M, Latasa MU, Mercado MR, Ruiz-Clavijo D, Saldaña C, Fernández-Urién I, Carrascosa J, Jusué V, Guerrero-Setas D, Zazpe C, González-Borja I, Sangro B, Herranz JM, Purroy A, Gil I, Nelson LJ, Vila JJ, Krawczyk M, Zieniewicz K, Patkowski W, Milkiewicz P, Cubero FJ, Alkorta-Aranburu G, G Fernandez-Barrena M, Urman JM, Berasain C, Avila MA. Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures. Gut 2022; 71:1141-1151. [PMID: 34285068 PMCID: PMC9120390 DOI: 10.1136/gutjnl-2021-325178] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 07/08/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). DESIGN A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. RESULTS An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. CONCLUSION Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.
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Affiliation(s)
- Maria Arechederra
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain,Navarra Institute for Health Research, IdiSNA, Pamplona, Spain
| | - María Rullán
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Irene Amat
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Pathology, Navarra University Hospital Complex, Pamplona, Spain
| | - Daniel Oyon
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Lucia Zabalza
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Maria Elizalde
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain
| | - M Ujue Latasa
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain,Navarra Institute for Health Research, IdiSNA, Pamplona, Spain
| | - Maria R Mercado
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Pathology, Navarra University Hospital Complex, Pamplona, Spain
| | - David Ruiz-Clavijo
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Cristina Saldaña
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Ignacio Fernández-Urién
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Juan Carrascosa
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Vanesa Jusué
- Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - David Guerrero-Setas
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Molecular Pathology of Cancer Group, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Pamplona, Spain
| | - Cruz Zazpe
- Department of General Surgery, Navarra University Hospital Complex, Pamplona, Spain
| | | | - Bruno Sangro
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Liver Unit, Dept. of Internal Medicine, Clinica Universitaria de Navarra, Pamplona, Spain,CIBEREHD, Madrid, Spain
| | - Jose M Herranz
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain,CIBEREHD, Madrid, Spain
| | - Ana Purroy
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Biobank Unit, Navarrabiomed, Pamplona, Spain
| | - Isabel Gil
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Biobank Unit, Navarrabiomed, Pamplona, Spain
| | - Leonard J Nelson
- Institute for Bioengineering, University of Edinburgh, Edinburgh, UK
| | - Juan J Vila
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany,Liver and Internal Medicine Unit, Medical University of Warsaw, Warszawa, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Waldemar Patkowski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland,Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Francisco Javier Cubero
- CIBEREHD, Madrid, Spain,Department of Immunology, Ophtalmology and ENT, School of Medicine, Complutense University of Madrid, Madrid, Spain
| | | | - Maite G Fernandez-Barrena
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain,Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,CIBEREHD, Madrid, Spain
| | - Jesus M Urman
- Navarra Institute for Health Research, IdiSNA, Pamplona, Spain,Department of Gastroenterology and Hepatology, Navarra University Hospital Complex, Pamplona, Spain
| | - Carmen Berasain
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain .,Navarra Institute for Health Research, IdiSNA, Pamplona, Spain.,CIBEREHD, Madrid, Spain
| | - Matias A Avila
- Hepatology Program, CIMA, University of Navarra, Pamplona, Spain .,Navarra Institute for Health Research, IdiSNA, Pamplona, Spain.,CIBEREHD, Madrid, Spain
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13
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Baroud S, Sahakian AJ, Sawas T, Storm AC, Martin JA, Abu Dayyeh BK, Topazian MD, Levy MJ, Roberts LR, Gores GJ, Petersen BT, Chandrasekhara V. Impact of trimodality sampling on detection of malignant biliary strictures compared with patients with primary sclerosing cholangitis. Gastrointest Endosc 2022; 95:884-892. [PMID: 34871554 DOI: 10.1016/j.gie.2021.11.029] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 11/12/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Malignant biliary strictures can be difficult to diagnose, with up to 20% considered indeterminate after initial tissue sampling. This study aimed to determine the performance characteristics of transpapillary biopsy sampling (TPB) and fluorescence in situ hybridization (FISH) in isolation or in combination with standard brush cytology (BC) in patients who received trimodality sampling for biliary strictures. METHODS This single-center retrospective cohort study included patients with biliary strictures undergoing ERCP with trimodality sampling between September 2014 and April 2019. Performance characteristics for each diagnostic test alone and in combination were calculated. RESULTS Two hundred four patients underwent trimodality biliary sampling, including 104 (51.0%) with malignancy. The diagnostic sensitivity for malignancy with BC (17.3%) significantly improved with dual modality (BC+FISH, 58.7%; BC+TPB, 40.4%) or trimodality sampling (68.3%; P < .001 for all comparisons). Trimodality sampling improved diagnostic sensitivity for malignancy compared with BC+FISH (P = .002) and BC+TPB (P < .001). There was no statistically significant difference in the sensitivity of trimodality sampling in detecting cholangiocarcinoma (79.7%) compared with pancreatic cancer (62.5%; P = .1). Among 57 patients with primary sclerosing cholangitis (PSC), the sensitivity of detecting biliary malignancy (n = 20) was 20% for BC and significantly improved with the addition of FISH (80%; P < .001) but not with TPB (35.0%; P = .25). Trimodality sampling did not further improve diagnostic sensitivity (85%) over BC+FISH (80%) for malignancy in the setting of PSC (P = 1). CONCLUSIONS Trimodality sampling improves the diagnostic sensitivity for the detection of malignant biliary strictures with no significant difference in sensitivity for cholangiocarcinoma compared with pancreatic cancer. However, in patients with PSC, trimodality sampling was not superior to BC+FISH.
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Affiliation(s)
- Serge Baroud
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Alexander J Sahakian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Tarek Sawas
- Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA
| | - Andrew C Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - John A Martin
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Barham K Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark D Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael J Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Bret T Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Vinay Chandrasekhara
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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14
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Wu B, Liu YJ, Rogers J, Liu YZ, Rabinovitch PS, Small T, Swanson PE, Yeh MM. Role of DNA Flow Cytometry in the Diagnosis of Malignancy in Bile Duct Biopsies Using Paraffin-Embedded Tissue. Am J Clin Pathol 2022; 157:417-425. [PMID: 34542607 DOI: 10.1093/ajcp/aqab130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES Histopathologic evaluation of bile biopsies for biliary strictures is frequently challenging and is affected by interobserver disagreement. Reliable ancillary tests that can help differentiate benign from malignant are not available. This study aimed to evaluate whether DNA content abnormalities detected by flow cytometry on formalin-fixed, paraffin-embedded (FFPE) tissue can help differentiate benign/reactive, dysplastic from malignant cell populations in bile duct biopsies. METHODS We performed DNA flow cytometry on 30 FFPE bile duct biopsies in 5 well-defined diagnostic categories: (1) negative for dysplasia (NED), (2) low-grade dysplasia (LGD), (3) high-grade dysplasia (HGD), (4) carcinoma (CA), and (5) indefinite for dysplasia (IND). RESULTS Abnormal DNA content was detected in 0 NED, 5 LGD (62.5%), 2 HGD (33.3%), 3 CA (60%), and 4 IND (80%) samples. As a diagnostic marker, the estimated sensitivity, specificity, positive predictive value, and negative predictive value were 63%, 100%, 100%, and 50%, respectively, for diagnosing HGD or CA. CONCLUSIONS DNA flow cytometry analysis is a useful ancillary test for the interpretation of bile duct biopsies. DNA content abnormalities, when correlated with histologic findings, will not only help confirm the morphologic impression but also identify patients who are at a higher risk of developing malignancy.
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Affiliation(s)
- Bicong Wu
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
| | - Yong-Jun Liu
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jessica Rogers
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
| | - Yao-Zhong Liu
- Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | | | - Thomas Small
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
| | - Paul E Swanson
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
- Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Matthew M Yeh
- Departments of Laboratory Medicine and Pathology, Seattle, WA, USA
- Medicine, University of Washington School of Medicine, Seattle, WA, USA
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15
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Stassen PMC, Goodchild G, de Jonge PJF, Erler NS, Anderloni A, Cennamo V, Church NI, Fernandez-Urien Sainz I, Huggett MT, James MW, Joshi D, Kylänpää L, Laleman W, Nayar MK, Oppong KW, Poley JW, Potts JR, Repici A, Udd M, Vila JJ, Wong T, Bruno MJ, Webster GJM. Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures. Gastrointest Endosc 2021; 94:1059-1068. [PMID: 34216597 DOI: 10.1016/j.gie.2021.06.027] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/22/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.
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Affiliation(s)
- Pauline M C Stassen
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - George Goodchild
- Department of Gastroenterology, University College London Hospitals, London, UK
| | - Pieter Jan F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nicole S Erler
- Department of Biostatistics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Andrea Anderloni
- Digestive Endoscopy Unit, Humanitas Clinical and Research Center, Milan, Italy
| | - Vincenzo Cennamo
- Gastroenterology and Interventional Endoscopy Unit, Local Health Authority of Bologna, Bologna, Italy
| | - Nicholas I Church
- Department of Gastroenterology and Hepatology, Lothian University Hospitals NHS Trust, Edinburgh, UK
| | | | - Matthew T Huggett
- Department of Gastroenterology, St James's University Hospital, Leeds, UK
| | - Martin W James
- Nottingham Digestive Disease Centre (NDDC) and NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University and Nottingham University Hospitals NHS Trust, Queens Medical Centre, Nottingham, UK
| | - Deepak Joshi
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Leena Kylänpää
- Department of Gastroenterological surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Wim Laleman
- Department of Gastroenterology and Hepatology, Section of Liver and Biliopancreatic disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Manu K Nayar
- HPB Unit Newcastle upon Tyne Hospitals, and Translational and Clinical Research Institute Newcastle University, Newcastle, UK
| | - Kofi W Oppong
- HPB Unit Newcastle upon Tyne Hospitals, and Translational and Clinical Research Institute Newcastle University, Newcastle, UK
| | - Jan-Werner Poley
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | - Alessandro Repici
- Digestive Endoscopy Unit, Humanitas Clinical and Research Center, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Marianne Udd
- Department of Gastroenterological surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Juan J Vila
- Department of Gastroenterology and Hepatology, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - Terence Wong
- Department of Gastroenterology and Hepatology, Guys and St Thomas' Hospital, London, UK
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - George J M Webster
- Department of Gastroenterology, University College London Hospitals, London, UK; Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
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16
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Ney A, Garcia-Sampedro A, Goodchild G, Acedo P, Fusai G, Pereira SP. Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum. Front Oncol 2021; 11:699401. [PMID: 34660269 PMCID: PMC8515053 DOI: 10.3389/fonc.2021.699401] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 09/15/2021] [Indexed: 12/12/2022] Open
Abstract
Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.
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Affiliation(s)
- Alexander Ney
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Andres Garcia-Sampedro
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - George Goodchild
- St. Bartholomew's hospital, Barts Health NHS Trust, London, United Kingdom
| | - Pilar Acedo
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Giuseppe Fusai
- Division of Surgery and Interventional Science - University College London, London, United Kingdom
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
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17
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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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18
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Jang SI, Nahm JH, Kwon NH, Jeong S, Lee TH, Cho JH, Kwon CI, Kim DU, Kim JM, Cho HD, Lee HS, Kim S, Lee DK. Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study. Gastrointest Endosc 2021; 94:733-741.e4. [PMID: 33965384 DOI: 10.1016/j.gie.2021.04.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/27/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).
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Affiliation(s)
- Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji Hae Nahm
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Nam Hoon Kwon
- Medicinal Bioconvergence Research Center, Institute for Artificial Intelligence and Biomedical Research, College of Pharmacy, Yonsei University, Incheon, Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea
| | - Tae Hoon Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, South Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Chang-Il Kwon
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | - Dong Uk Kim
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University School of Medicine, Pusan, South Korea
| | - Joon Mee Kim
- Department of Pathology, Inha University School of Medicine, Incheon, South Korea
| | - Hyun Deuk Cho
- Department of Pathology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, South Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sunghoon Kim
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Institute for Artificial Intelligence and Biomedical Research, College of Pharmacy & College of Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
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19
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Huynh R, Owers C, Pinto C, Nguyen TM, Kwok T. Endoscopic Evaluation of Biliary Strictures: Current and Emerging Techniques. Clin Endosc 2021; 54:825-832. [PMID: 34038998 PMCID: PMC8652159 DOI: 10.5946/ce.2021.048] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 02/17/2021] [Indexed: 11/25/2022] Open
Abstract
The diagnosis of biliary strictures in clinical practice can be challenging. Discriminating between benign and malignant biliary strictures is important to prevent the morbidity and mortality associated with incorrect diagnoses. Missing a malignant biliary stricture may delay surgery, resulting in poor prognostic outcomes. Conversely, it has been demonstrated that approximately 20% of patients who undergo surgery for suspected biliary malignancies have a benign etiology on histopathology. Traditional tissue sampling using endoscopic retrograde cholangiography does not always produce a definitive diagnosis, with a considerable proportion of cases remaining as indeterminate biliary strictures. Recent advances in endoscopic techniques have the potential to improve the diagnostic and prognostic accuracy of biliary strictures.
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Affiliation(s)
- Roy Huynh
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Corinne Owers
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Christopher Pinto
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Thuy-My Nguyen
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - Titus Kwok
- Department of Upper Gastrointestinal Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia
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20
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Rompianesi G, Di Martino M, Gordon-Weeks A, Montalti R, Troisi R. Liquid biopsy in cholangiocarcinoma: Current status and future perspectives. World J Gastrointest Oncol 2021; 13:332-350. [PMID: 34040697 PMCID: PMC8131901 DOI: 10.4251/wjgo.v13.i5.332] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.
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Affiliation(s)
- Gianluca Rompianesi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Marcello Di Martino
- Hepato-Bilio-Pancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Alex Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Roberto Montalti
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Roberto Troisi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
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21
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Acher AW, Weber SM, Pawlik TM. Liver transplantation for perihilar cholangiocarcinoma: patient selection and outcomes. Expert Rev Gastroenterol Hepatol 2021; 15:555-566. [PMID: 33577361 DOI: 10.1080/17474124.2021.1890584] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Introduction: Peri-hilar cholangiocarcinoma is an aggressive bile duct cancer. Long-term survival is possible with margin-negative surgery. Historically, unresectable disease was approached with non-curative treatment options. In recent decades, an innovative approach of neoadjuvant chemoradiation and liver transplantation has demonstrated long-term survival for highly selected patients.Areas covered: This is a critical analysis of studies published to date on neoadjuvant chemoradiation and liver transplantation for selected patients with peri-hilar cholangiocarcinoma. A PubMed literature search was conducted for years 1970-2020 with the following search criteria: ['hilar' OR 'peri-hilar' AND 'cholangiocarcinoma'] AND ['treatment' OR 'transplantation' OR 'survival' OR 'outcome']; 'neoadjuvant chemoradiation' AND 'unresectable cholangiocarcinoma'. All peer-reviewed original research studies were selected for review.Expert opinion: Neoadjuvant chemoradiation and liver transplantation for patients with early stage unresectable peri-hilar cholangiocarcinoma can achieve long-term survival in highly selected patients who survive to transplantation without disease progression. There are observed differences in survival for patients with PSC-associated versus de novo cholangiocarcinoma and transplanted versus resected patients; however, these differences are not contextualized by established tumor and patient factors that influence recurrence and survival. Therefore, these results must be interpreted within the limitations of the study designs upon which they are based.
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Affiliation(s)
- Alexandra W Acher
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Sharon M Weber
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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22
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Kamp EJCA, Dinjens WNM, Doukas M, Bruno MJ, de Jonge PJF, Peppelenbosch MP, de Vries AC. Optimal tissue sampling during ERCP and emerging molecular techniques for the differentiation of benign and malignant biliary strictures. Therap Adv Gastroenterol 2021; 14:17562848211002023. [PMID: 33948111 PMCID: PMC8053835 DOI: 10.1177/17562848211002023] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 02/15/2021] [Indexed: 02/04/2023] Open
Abstract
Patients with cholangiocarcinoma have poor survival since the majority of patients are diagnosed at a stage precluding surgical resection, due to locally irresectable tumors and/or metastases. Optimization of diagnostic strategies, with a principal role for tissue diagnosis, is essential to detect cancers at an earlier stage amenable to curative treatment. Current barriers for a tissue diagnosis include both insufficient tissue sampling and a difficult cyto- or histopathological assessment. During endoscopic retrograde cholangiopancreatography, optimal brush sampling includes obtaining more than one brush within an individual patient to increase its diagnostic value. Currently, no significant increase of the diagnostic accuracy for the new cytology brush devices aiming to enhance the cellularity of brushings versus standard biliary brush devices has been demonstrated. Peroral cholangioscopy with bile duct biopsies appears to be a valuable tool in the diagnostic work-up of indeterminate biliary strictures, and may overcome current technical difficulties of fluoroscopic-guided biopsies. Over the past years, molecular techniques to detect chromosomal instability, mutations and methylation profiling of tumors have revolutionized, and implementation of these techniques on biliary tissue during diagnostic work-up of biliary strictures may be awaited in the near future. Fluorescence in situ hybridization has already been implemented in routine diagnostic evaluation of biliary strictures in several centers. Next-generation sequencing is promising for standard diagnostic care in biliary strictures, and recent studies have shown adequate detection of prevalent genomic alterations in KRAS, TP53, CDKN2A, SMAD4, PIK3CA, and GNAS on biliary brush material. Detection of DNA methylation of tumor suppressor genes and microRNAs may evolve over the coming years to a valuable diagnostic tool for cholangiocarcinoma. This review summarizes optimal strategies for biliary tissue sampling during endoscopic retrograde cholangiopancreatography and focuses on the evolving molecular techniques on biliary tissue to improve the differentiation of benign and malignant biliary strictures.
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Affiliation(s)
- Eline J. C. A. Kamp
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Winand N. M. Dinjens
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Pieter Jan F. de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, Room Na-609, Rotterdam, 3015 GD, The Netherlands
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23
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Raine T, Thomas JP, Brais R, Godfrey E, Carroll NR, Metz AJ. Test performance and predictors of accuracy of endoscopic ultrasound-guided fine-needle aspiration for diagnosing biliary strictures or masses. Endosc Int Open 2020; 8:E1537-E1544. [PMID: 33140008 PMCID: PMC7577792 DOI: 10.1055/a-1231-4948] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022] Open
Abstract
Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has emerged as an important method for obtaining a preoperative tissue diagnosis for suspected cholangiocarcinoma. However, doubts remain about test sensitivity. This study assessed the value and limitations of EUS-FNA in clinical practice. Patients and methods Patients undergoing EUS-FNA for biliary strictures/masses at a UK tertiary referral center from 2005 to 2014 were prospectively enrolled. Data on EUS-FNA findings, histology, and endoscopy and patient outcomes were collected to evaluate test performance and identify factors predictive of an inaccurate diagnostic result. Results Ninety-seven patients underwent a total of 112 EUS-FNA procedures. Overall test sensitivity for an initial EUS-FNA for suspected cholangiocarcinoma was 75 % (95 % CI 64 %-84 %), with specificity 100 % (95 % CI 85 %-100 %) and negative predictive value 0.62 (95 % CI 0.47-0.75). Hilar lesions, the presence of a biliary stent, and a diagnosis of PSC were significantly independently associated with an inaccurate result. For the most difficult cases, repeat sampling and use of the Papanicolaou cytopathology grading scale led to an increase in test sensitivity from 17 % to 100 % ( P = 0.015) with no loss of specificity. Conclusions EUS-FNA was found to be a useful method for obtaining a preoperative tissue diagnosis for patients with suspected cholangiocarcinoma. This study identified markers that can reduce test accuracy and measures that can improve test performance of EUS-FNA.
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Affiliation(s)
- Tim Raine
- Division of Gastroenterology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK
| | - John P. Thomas
- Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK
| | - Rebecca Brais
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Edmund Godfrey
- Department of Endoscopy, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nicholas R. Carroll
- Department of Endoscopy, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Andrew J. Metz
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, Australia
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24
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Liu YJ, Rogers J, Liu YZ, Gui X, Jalikis F, Koch L, Swanson PE, Truong CD, Yeh MM. Interobserver agreement in pathologic evaluation of bile duct biopsies. Hum Pathol 2020; 107:29-38. [PMID: 33129823 DOI: 10.1016/j.humpath.2020.10.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 10/07/2020] [Accepted: 10/12/2020] [Indexed: 12/20/2022]
Abstract
Intraductal biopsy is commonly used for preoperative evaluation of the etiology of biliary strictures. Interpretation of intraductal biopsies is frequently challenging. The diagnosis often suffers from interobserver disagreement, which has not been studied in the literature. We sought to assess interobserver concordance in the interpretation of intraductal biopsies. Eighty-five biopsies were retrieved, falling into five diagnostic categories: negative for dysplasia (NED), indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and carcinoma (CA). Eight gastrointestinal pathologists blindly reviewed all the slides. Agreement among pathologists was analyzed using Fleiss κ and weighted concordance coefficient S∗. A face-to-face consensus/training session was held to discuss the classification criteria, followed by a second round review. The overall interobserver agreement was fair in the first round review (κ = 0.39; S∗ = 0.56) and improved to moderate in the second round review (κ = 0.48; S∗ = 0.69). The agreement before and after consensus meeting was substantial to nearly perfect for CA (κ = 0.65, S∗ = 0.83; and κ = 0.80, S∗ = 0.91), fair for HGD (κ = 0.28, S∗ = 0.69; and κ = 0.40, S∗ = 0.63), and moderate for NED (κ = 0.47, S∗ = 0.50; and κ = 0.47, S∗ = 0.53). Agreement improved from fair to moderate for LGD (κ = 0.36, S∗ = 0.61; and κ = 0.49, S∗ = 0.71) and slight to fair for IND (κ = 0.16, S∗ = 0.51; and κ = 0.33, S∗ = 0.50). Compared with Hollande's fixed specimens, the agreement was higher in almost all diagnostic categories in formalin-fixed biopsies. Overall, interobserver concordance was improved after a consensus/training session. Interobserver reproducibility was high at the end of the diagnostic spectrum (CA) but fair to moderate for other diagnostic categories.
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Affiliation(s)
- Yong-Jun Liu
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, WI, 53705, USA
| | - Jessica Rogers
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Yao-Zhong Liu
- Department of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, LA, 70112, USA
| | - Xianyong Gui
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Florencia Jalikis
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Lisa Koch
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Paul E Swanson
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Camtu D Truong
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA
| | - Matthew M Yeh
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98195, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA.
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25
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Harbhajanka A, Michael CW, Janaki N, Gokozan HN, Wasman J, Bomeisl P, Yoest J, Sadri N. Tiny but mighty: use of next generation sequencing on discarded cytocentrifuged bile duct brushing specimens to increase sensitivity of cytological diagnosis. Mod Pathol 2020; 33:2019-2025. [PMID: 32457409 DOI: 10.1038/s41379-020-0577-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 05/15/2020] [Accepted: 05/15/2020] [Indexed: 12/12/2022]
Abstract
Bile duct brushing (BDB) is used to evaluate pancreatobiliary lesions as it widely samples lesions with a low complication rate. Cytological evaluation of BDB is a specific but insensitive test. There is limited literature on the use of post-cytocentrifuged (PCC) samples, which are usually discarded, for next-generation sequencing (NGS) as an adjunct to cytological diagnosis of BDB. In this study we investigate whether molecular analysis by NGS of PCC specimens improves the sensitivity of diagnosis. PCC samples from 100 consecutive BDB specimens spanning 93 unique patients were retained. DNA was extracted and mutational analysis was performed agnostic of morphologic or clinical findings. Each BDB specimen was characterized as negative, atypical or positive based on morphological analysis by trained cytopathologists. Performance characteristics for mutational profiling and morphological analysis were calculated on the basis of clinicopathologic follow-up. There was sufficient clinicopathologic follow-up to classify 94 of 100 cases as either malignant (n = 43) or benign (n = 51). Based on morphologic analysis of cytology, these 94 cases were classified as either benign (n = 55), atypical (n = 18), or as at least suspicious or positive for malignancy (n = 21). Morphologic analysis of cytology showed a sensitivity of 49% and a specificity of 100% if atypical cases were considered negative. NGS revealed oncogenic alterations in 40/43 (93%) of malignant cases based on clinicopathologic follow-up. The most common alterations were in KRAS and TP53, observed in 77% and 49% of malignant cases respectively. No alterations were observed in the 51 benign cases classified based on clinicopathologic follow-up. Supplementing cytomorphologic analysis with molecular profiling of PCC by targeted NGS analysis increased the sensitivity to 93% and maintained specificity at 100%. This study provides evidence for the utility of NGS molecular profiling of PCC specimens to increase the sensitivity of BDB cytology samples, although studies with larger cohorts are needed to verify these findings.
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Affiliation(s)
- Aparna Harbhajanka
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Claire W Michael
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Nafiseh Janaki
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School Boston, Boston, MA, USA
| | - Hamza N Gokozan
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jay Wasman
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Philip Bomeisl
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jennifer Yoest
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Navid Sadri
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
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Jang SI, Kwon NH, Lim BJ, Nahm JH, Park JS, Kang CM, Park SR, Lee Sd SY, Kang BS, Kim S, Lee DK. New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer. Gastrointest Endosc 2020; 92:310-319.e6. [PMID: 31874158 DOI: 10.1016/j.gie.2019.12.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 12/10/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Identifying malignant biliary strictures using endobiliary brushing cytology specimens is important for treatment decision-making and prognosis prediction. The sensitivity of brushing cytology specimens based on Papanicolaou (Pap) staining is low, which hampers accurate diagnosis of indeterminate strictures. Here, we assessed the diagnostic value of immunohistochemical (IHC) and immunofluorescence (IF) staining for methionyl-tRNA synthetase 1 (MARS1). METHODS Endobiliary brushing cytology specimens were obtained during ERCP from 80 patients with an extrahepatic biliary stricture. Pap and MARS1 IF staining were performed on liquid-based cytology slides derived from these specimens. Sections of bile duct adenocarcinoma and normal bile duct tissue were obtained from 45 patients who underwent surgery for malignant biliary stricture, and MARS1 levels were evaluated by IHC staining. RESULTS MARS1 IF staining was applied to brushing cytology specimens, and the results showed strong signals in malignant biliary structures but not in the negative for malignancy specimens. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 70.4%, 96.2%, 97.4%, 56.8%, and 78.8%, respectively, for conventional Pap staining and 98.1%, 96.1%, 98.1%, 96.2%, and 97.5%, respectively, for MARS1 IF (P < .0001). When IHC staining was used, MARS1 was detected in 45 bile duct adenocarcinoma sections but not in 15 normal bile duct sections. Moreover, MARS1 mRNA and protein levels were significantly higher in bile duct adenocarcinoma sections according to polymerase chain reaction and Western blot, respectively. CONCLUSIONS The high sensitivity and accuracy of MARS1 IF staining enabled detection of malignancy in patients with indeterminate biliary stricture. Further prospective studies are needed to validate our findings. (Clinical trial registration number: KCT 0003285.).
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Affiliation(s)
- Sung Ill Jang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Nam Hoon Kwon
- Medicinal Bioconvergence Research Center, Seoul National University, Suwon, Gyeonggi-do, Korea
| | - Beom Jin Lim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Hae Nahm
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Seong Park
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Gangnam Severance Hospital and Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - So Ra Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Su Yun Lee Sd
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Sik Kang
- School of Life Science and Biotechnology, Kyungpook National University, Daegu, Korea
| | - Sunghoon Kim
- Medicinal Bioconvergence Research Center, Seoul National University, Suwon, Gyeonggi-do, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Gyeonggi-do, Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Jang S, Stevens T, Kou L, Vargo JJ, Parsi MA. Efficacy of digital single-operator cholangioscopy and factors affecting its accuracy in the evaluation of indeterminate biliary stricture. Gastrointest Endosc 2020; 91:385-393.e1. [PMID: 31541625 DOI: 10.1016/j.gie.2019.09.015] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 09/08/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Indeterminate biliary stricture remains a significant diagnostic challenge. The current method of ERCP with bile duct brush cytology has substantial room for improvement. We aimed to determine the efficacy of a digital single-operator cholangioscopy (DSOC) in evaluation of indeterminate biliary stricture. METHODS An observational cohort study was conducted among the patients who underwent DSOC for the indication of indeterminate biliary stricture at a tertiary academic medical center. The outcomes of interests were the accuracy of DSOC in visual interpretation and bile duct sample and identification of any factor(s) that could influence its effectiveness. RESULTS One hundred five patients were included. The overall accuracy of DSOC in visual interpretation was 89.5%, whereas the accuracy of bile duct sample was 83.2%. The sensitivities of visual impression and bile duct sample were 89.1% and 69.8% and their specificities were 90% and 97.9%, respectively. The degree of endoscopists' experience with fewer than 25 cases and the severity of hyperbilirubinemia negatively impacted the accuracy of DSOC. Among 55 patients with definitive diagnosis of malignant stricture, the sensitivity of combined intraductal forceps biopsy sampling and brush cytology was 80.6%, whereas the sensitivity of brush cytology alone was 47.1%. CONCLUSIONS DSOC augments ERCP in evaluating indeterminate biliary stricture. The acquisition of intraductal forceps biopsy samples should be a requisite in evaluation of indeterminate biliary stricture with DSOC. Discovery of modifiable factors such as the degree of endoscopists' expertise and the severity of hyperbilirubinemia, which can influence the accuracy of DSOC, warrants further studies on patient preprocedure optimization and an endoscopic training program that will cultivate procedural competency.
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Affiliation(s)
- Sunguk Jang
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Tyler Stevens
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lei Kou
- Department of Quantitative Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - John J Vargo
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Mansour A Parsi
- Department of Gastroenterology and Hepatology, Tulane University, New Orleans, Louisiana, USA
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Singhi AD, Nikiforova MN, Chennat J, Papachristou GI, Khalid A, Rabinovitz M, Das R, Sarkaria S, Ayasso MS, Wald AI, Monaco SE, Nalesnik M, Ohori NP, Geller D, Tsung A, Zureikat AH, Zeh H, Marsh JW, Hogg M, Lee K, Bartlett DL, Pingpank JF, Humar A, Bahary N, Dasyam AK, Brand R, Fasanella KE, McGrath K, Slivka A. Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. Gut 2020; 69:52-61. [PMID: 30971436 PMCID: PMC6943248 DOI: 10.1136/gutjnl-2018-317817] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 03/25/2019] [Accepted: 03/27/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.
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Affiliation(s)
- Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Marina N Nikiforova
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Jennifer Chennat
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Asif Khalid
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Rohit Das
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Savreet Sarkaria
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - M Samir Ayasso
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Abigail I Wald
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Sara E Monaco
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - Michael Nalesnik
- Department of Pathology, Division of Transplant Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - N Paul Ohori
- Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA
| | - David Geller
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Allan Tsung
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Herbert Zeh
- Department of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas, USA
| | - J Wallis Marsh
- Department of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA
| | - Melissa Hogg
- Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA
| | - Kenneth Lee
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - David L Bartlett
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - James F Pingpank
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Abhinav Humar
- Department of Transplant, Thomas E Starzl Transplant Instiute University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Division of Hematology and Oncology, UPMC Cancer Centers, Pittsburgh, Pennsylvania, USA
| | - Anil K Dasyam
- Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Randall Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth E Fasanella
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kevin McGrath
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Peroral cholangioscopy with cholangioscopy-directed biopsies in the diagnosis of biliary malignancies: a systemic review and meta-analysis. Eur J Gastroenterol Hepatol 2019; 31:935-940. [PMID: 30896553 DOI: 10.1097/meg.0000000000001402] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Accurate diagnosis is essential in the appropriate management of biliary strictures. Our aim is to evaluate the efficacy of cholangioscopy-directed biopsies in differentiating biliary intraductal malignancies from benign lesions. MATERIALS AND METHODS Articles were searched in Medline, PubMed, and Ovid journals. Pooling was performed by both fixed-effects and random-effects models. Only studies from which a 2×2 table could be constructed for true-positive, false-negative, false-positive, and true-negative values were included. RESULTS Initial search identified 2110 reference articles for peroral cholangioscopy; of these, 160 relevant articles were selected and reviewed. Data were extracted from 15 studies (N=539) that fulfilled the inclusion criteria. Pooled sensitivity of cholangioscopy-directed biopsies in diagnosing malignancy was 71.9% [95% confidence interval (CI): 66.1-77.1] and pooled specificity was 99.1% (95% CI: 96.9-99.9). The positive likelihood ratio of cholangioscopy-directed biopsies was 18.1 (95% CI: 9.1-35.8), whereas the negative likelihood ratio was 0.3 (95% CI: 0.2-0.4). The pooled diagnostic odds ratio was 71.6 (95% CI: 32.8-156.4). All the pooled estimates calculated by fixed-effects and random-effect models were similar. Summary receiver operating characteristic curves showed an area under the curve of 0.98. The χ heterogeneity for all the pooled accuracy estimates was 5.62 (P=0.96). CONCLUSION Peroral cholangioscopy with cholangioscopy-directed biopsies has a high specificity in differentiating intraductal malignancies from benign lesions. Cholangioscopy-directed biopsies should be strongly considered for biliary stricture evaluation.
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Prat F, Leblanc S, Foissac F, Ponchon T, Laugier R, Bichard P, Maire F, Coumaros D, Charachon A, Vedrenne B, Boytchev I, Chaussade S, Kaddour N, Laquière A, Gaujoux S. Impact of peroral cholangioscopy on the management of indeterminate biliary conditions: a multicentre prospective trial. Frontline Gastroenterol 2019; 10:236-243. [PMID: 31281624 PMCID: PMC6583565 DOI: 10.1136/flgastro-2018-100985] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 10/10/2018] [Accepted: 10/18/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Single-operator cholangioscopy (SOC) can help diagnose biliopancreatic conditions. The impact of SOC on patient outcome has never been specifically addressed. PATIENTS AND METHODS Consecutive patients bearing indeterminate biliary strictures (IDBS), or primary sclerosing cholangitis (PSC) with suspected cholangiocarcinoma, were included. Patients with IDBS had at least one previous inconclusive endoscopic retrograde cholangio pancreatography (ERCP) + cytology. Primary endpoint was the difference in adequacy of management planned before and after SOC with regard to final diagnosis obtained after surgery or 24 months follow-up. DESIGN Prospective open-label multicentre trial. RESULTS 61 patients were included (IDBS: 48; PSC: 13); 70.5% had a benign lesion (IDBS 66.7%, PSC 84.6%). The management adequacy rate was significantly higher after SOC than before SOC overall (p<10-5), in IDBS (p<0.001) and PSC (p<0.05) patients. SOC induced changes in the management of the majority of patients in all groups (60.3%). The overall sensitivity of combined visual impression and biopsy ranged from 52% to 63.6% depending on investigator or independent expert rating (κ 0.92-0.96), whereas specificity, positive and negative predictive values of SOC were, respectively, 100%, 100% and 83.6%. Patient management observed at the end of follow-up was consistent with that anticipated after SOC in 88.5% overall. CONCLUSION Despite a moderate sensitivity for the diagnosis of malignancy, SOC has a dramatic impact on the management of patients with IDBS and PSC with suspected carcinoma. Cholangioscopy might be implemented in the workup of selected patients with challenging diagnosis, when a significant impact on outcome (essentially resection vs conservative management) is to be expected.
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Affiliation(s)
- Frederic Prat
- Department of Gastroenterology, Assistance Publique Hopitaux de Paris, Paris-Descartes University, Paris, France
| | - Sarah Leblanc
- Department of Gastroenterology, Assistance Publique Hopitaux de Paris, Paris-Descartes University, Paris, France
| | | | | | - René Laugier
- Gastroenterology, Assistance Publique Hopitaux de Marseille, Marseille, France
| | - Philippe Bichard
- Digestive Endoscopy Unit, Centre Hospitalier Universitaire de Grenoble, Grenoble, France,Service de Gastro-entérologie et Hépatologie, Hopitaux Universitaires de Geneve, Geneva, Switzerland
| | | | | | | | - Bruno Vedrenne
- Groupe Hospitalier de la Region de Mulhouse et Sud Alsace, Mulhouse, France
| | | | | | | | - Arthur Laquière
- Gastroenterology and Endoscopy Unit, Hopital st joseph, Marseille, France
| | - Sèbastien Gaujoux
- Department of Surgery, Assistance Publique - Hopitaux de Paris, Paris, France
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31
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Goyal A, Sharaiha RZ, Alperstein SA, Siddiqui MT. Cytologic diagnosis of adenocarcinoma on bile duct brushings in the presence of stent associated changes: A retrospective analysis. Diagn Cytopathol 2018; 46:826-832. [DOI: 10.1002/dc.24052] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 06/22/2018] [Accepted: 07/17/2018] [Indexed: 12/16/2022]
Affiliation(s)
- Abha Goyal
- Department of Pathology and Laboratory Medicine; Weill Cornell Medicine - New York Presbyterian Hospital; New York New York
| | - Reem Z. Sharaiha
- Department of Pathology and Laboratory Medicine; Weill Cornell Medicine - New York Presbyterian Hospital; New York New York
| | - Susan A. Alperstein
- Department of Pathology and Laboratory Medicine; Weill Cornell Medicine - New York Presbyterian Hospital; New York New York
| | - Momin T. Siddiqui
- Department of Pathology and Laboratory Medicine; Weill Cornell Medicine - New York Presbyterian Hospital; New York New York
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Lee HJ, Cho KB. Diagnosis of Malignant Biliary Stricture: More is Better. Clin Endosc 2018; 51:115-117. [PMID: 29618174 PMCID: PMC5903087 DOI: 10.5946/ce.2018.035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/09/2018] [Accepted: 03/10/2018] [Indexed: 12/27/2022] Open
Affiliation(s)
- Hyun Jik Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kwang Bum Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
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Xie C, Aloreidi K, Patel B, Ridgway T, Thambi-Pillai T, Timmerman G, Khan A, Atiq M. Indeterminate biliary strictures: a simplified approach. Expert Rev Gastroenterol Hepatol 2018; 12:189-199. [PMID: 29034764 DOI: 10.1080/17474124.2018.1391090] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pre-operative evaluation of biliary strictures remains challenging. The dilemma that exists is how to balance the risk of failing to detect malignancy and the potential morbidity caused by unnecessary surgery in patients with benign etiologies. With emerging novel diagnostic modalities, this study aims to assess the efficacy of diagnostic techniques and facilitate a clinical approach to indeterminate biliary strictures. Areas covered: Conventional imaging modalities are crucial in identifying the location of a stricture and are helpful for choosing further diagnostic modalities. Utilization of endoscopic techniques, including endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), is key in establishing a diagnosis. The emergence of novel diagnostic modalities, such as fluorescence in-situ hybridization (FISH), peroral cholangioscopy (POC), intraductal endoscopic ultrasound (IDUS) and confocal laser endomicroscopy (CLE), enhance the diagnostic yield in the evaluation of indeterminate biliary strictures. Expert commentary: More reliable and validated visual criteria for differentiating malignancy from benign biliary conditions, utilizing advanced imaging modalities such as POC and CLE, need to be established. It is of significance to further evaluate these novel diagnostic modalities through ongoing trials and to develop a diagnostic algorithm that reconciles cost-effectiveness with diagnostic accuracy.
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Affiliation(s)
- Chencheng Xie
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Khalil Aloreidi
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Bhavesh Patel
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Timothy Ridgway
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Thavam Thambi-Pillai
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Gary Timmerman
- a Internal Medicine , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
| | - Adeel Khan
- c Surgery , Washington University in St. Louis , St. Louis , MO , USA
| | - Muslim Atiq
- b Surgery , University of South Dakota Sanford School of Medicine , Sioux Falls , SD , USA
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Berretta M, Cavaliere C, Alessandrini L, Stanzione B, Facchini G, Balestreri L, Perin T, Canzonieri V. Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications. Oncotarget 2017; 8:14192-14220. [PMID: 28077782 PMCID: PMC5355172 DOI: 10.18632/oncotarget.13929] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 10/28/2016] [Indexed: 12/12/2022] Open
Abstract
HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.
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Affiliation(s)
| | - Carla Cavaliere
- Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto Taranto, Italy
| | - Lara Alessandrini
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
| | - Brigida Stanzione
- Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy
| | - Gaetano Facchini
- Department of Medical Oncology, National Cancer Institute, "G. Pascale" Foundation, Naples, Italy
| | - Luca Balestreri
- Department of Radiology, National Cancer Institute, Aviano (PN), Italy
| | - Tiziana Perin
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
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Yamabe A, Irisawa A, Shibukawa G, Sato A, Fujisawa M, Arakawa N, Yoshida Y, Igarashi R, Maki T, Yamamoto S, Ikeda T, Abe Y, Hoshi K. Inflammatory Bile Duct Obstruction during the Healing Stage of Severe Acute Pancreatitis. Intern Med 2017; 56:1037-1040. [PMID: 28458308 PMCID: PMC5478563 DOI: 10.2169/internalmedicine.56.7859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The patient was a 62-year-old woman with a history of severe acute pancreatitis complicated by walled-off necrosis (WON), who developed obstructive jaundice during the recovery phase from WON. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) revealed the complete obstruction of the distal bile duct, and endoscopic ultrasonography (EUS) revealed thickening of the duct wall, with a uniform distribution, and a relatively well-preserved layered structure. A cytopathological examination using ERCP showed no malignancy. The underlying etiology of this case may have been the formation of a cicatricial stricture during the resolution of WON, in addition to fibrosis caused by the spreading of inflammation from pancreatitis.
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Affiliation(s)
- Akane Yamabe
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Atsushi Irisawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Goro Shibukawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Ai Sato
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Mariko Fujisawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Noriyuki Arakawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Yoshitsugu Yoshida
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Ryo Igarashi
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Takumi Maki
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Shogo Yamamoto
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Tsunehiko Ikeda
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Yoko Abe
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
| | - Koki Hoshi
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Japan
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Park YK, Choi JE, Jung WY, Song SK, Lee JI, Chung CW. Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: a case report with literature review. World J Surg Oncol 2016; 14:167. [PMID: 27343073 PMCID: PMC4919877 DOI: 10.1186/s12957-016-0928-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 06/22/2016] [Indexed: 02/07/2023] Open
Abstract
Background Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin’s lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature. Case presentation An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence. Conclusions In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin’s lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.
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Affiliation(s)
- Yong Keun Park
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea
| | - Jee Eun Choi
- Catholic Kwandong University College of Medicine, Incheon, South Korea
| | - Woon Yong Jung
- Department of Pathology, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea
| | - Sung Kyu Song
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea
| | - Jong In Lee
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea
| | - Chul-Woon Chung
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Incheon, South Korea.
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Onda S, Ogura T, Kurisu Y, Masuda D, Sano T, Takagi W, Fukunishi S, Higuchi K. EUS-guided FNA for biliary disease as first-line modality to obtain histological evidence. Therap Adv Gastroenterol 2016; 9:302-12. [PMID: 27134660 PMCID: PMC4830098 DOI: 10.1177/1756283x15625584] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Few reports have described endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) for biliary lesions. In addition, adverse events were not completely examined in previous reports, due to the inclusion of cases in which biliary stents had already been placed. The present study aimed to investigate the diagnostic yield and adverse events of EUS-FNA for biliary lesions as the first-line diagnostic modality for consecutive prospectively registered patients. METHODS Inclusion criteria were as follows: (1) patients with suspected cholangiocarcinoma (CCA) based on computed tomography or other imaging modalities; (2) patients who had not previously undergone endoscopic retrograde cholangiopancreatography or EUS-FNA; (3) absence of surgically altered anatomy, such as Roux-en-Y anastomosis or duodenal obstruction caused by tumor invasion, through which an endoscope could not pass; and (4) provision of written informed consent to all procedures associated with the study. RESULTS A total of 47 consecutive patients with suspected CCA were registered to this study. Sensitivity and accuracy were 89% and 87%, respectively. On multivariate analysis, puncture site was the only factor associated with reduced diagnostic yield (hazard ration, 6.879; 95% confidence interval, 1.172-40.374; P = 0.033). Remarkably, no adverse events such as bleeding or bile leakage were associated with EUS-FNA in any of the 47 patients. CONCLUSIONS Our results suggest that EUS-FNA can be safely performed for biliary disease without biliary stenting. Furthermore, this procedure may warrant use as the first-line diagnostic method, although our results need to be validated in future prospective studies.
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Affiliation(s)
- Saori Onda
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | | | | | - Daisuke Masuda
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Tatsushi Sano
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Wataru Takagi
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Kazuhide Higuchi
- Second Department of Internal Medicine, Osaka Medical College, Japan
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Brijbassie A, Yeaton P. Approach to the patient with a biliary stricture. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2016. [DOI: 10.1016/j.tgie.2016.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Mar WA, Shon AM, Lu Y, Yu JH, Berggruen SM, Guzman G, Ray CE, Miller F. Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation. Abdom Radiol (NY) 2016; 41:553-67. [PMID: 26847022 DOI: 10.1007/s00261-015-0583-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cholangiocarcinoma, a tumor of biliary epithelium, is increasing in incidence. The imaging appearance, behavior, and treatment of cholangiocarcinoma differ according to its location and morphology. Cholangiocarcinoma is usually classified as intrahepatic, perihilar, or distal. The three morphologies are mass-forming, periductal sclerosing, and intraductal growing. As surgical resection is the only cure, prompt diagnosis and accurate staging is crucial. In staging, vascular involvement, longitudinal spread, and lymphadenopathy are important to assess. The role of liver transplantation for unresectable peripheral cholangiocarcinoma will be discussed. Locoregional therapy can extend survival for those with unresectable intrahepatic tumors. The main risk factors predisposing to cholangiocarcinoma are parasitic infections, primary sclerosing cholangitis, choledochal cysts, and viral hepatitis. Several inflammatory conditions can mimic cholangiocarcinoma, including IgG4 disease, sclerosing cholangitis, Mirizzi's syndrome, and recurrent pyogenic cholangitis. The role of PET in diagnosis and staging will also be discussed. Radiologists play a crucial role in diagnosis, staging, and treatment of this disease.
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Affiliation(s)
- Winnie A Mar
- Department of Radiology, University of Illinois at Chicago, 1740 W Taylor St Rm 2483, MC 931, Chicago, IL, 60612, USA.
| | - Andrew M Shon
- Department of Radiology, University of Illinois at Chicago, 1740 W Taylor St Rm 2483, MC 931, Chicago, IL, 60612, USA
| | - Yang Lu
- Department of Radiology, University of Illinois at Chicago, 1740 W Taylor St Rm 2483, MC 931, Chicago, IL, 60612, USA
| | - Jonathan H Yu
- Department of Radiology, University of Illinois at Chicago, 1740 W Taylor St Rm 2483, MC 931, Chicago, IL, 60612, USA
| | - Senta M Berggruen
- Department of Radiology, Northwestern University, NMH/Arkes Family Pavilion Suite 800, 676 N Saint Clair, Chicago, IL, 60611, USA
| | - Grace Guzman
- Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Suite 130 CSN, MC 847, Chicago, IL, 60612, USA
| | - Charles E Ray
- Department of Radiology, University of Illinois at Chicago, 1740 W Taylor St Rm 2483, MC 931, Chicago, IL, 60612, USA
| | - Frank Miller
- Department of Radiology, Northwestern University, NMH/Arkes Family Pavilion Suite 800, 676 N Saint Clair, Chicago, IL, 60611, USA
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Abstract
Biliary strictures frequently present a diagnostic challenge during pre-operative evaluation to determine their benign or malignant nature. A variety of benign conditions, such as primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis, frequently mimic malignancies. In addition, PSC and other chronic biliary diseases increase the risk of cholangiocarcinoma and so require ongoing vigilance. Although traditional methods of evaluation including imaging, detection of circulating tumour markers, and sampling by endoscopic ultrasound and endoscopic retrograde cholangiopancreatography have a high specificity, they suffer from low sensitivity. Currently, up to 20% of biliary strictures remain indeterminate after pre-operative evaluation and necessitate surgical intervention for a definitive diagnosis. The discovery of novel biomarkers, new imaging modalities and advanced endoscopic techniques suggests that a multimodality approach might lead to better diagnostic accuracy.
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Furnée EJB, Spoto C, de Graaf MJ, Smakman N. Enterobius vermicularis infection of the liver in a patient with colorectal carcinoma with suspected liver metastasis. BMJ Case Rep 2015; 2015:bcr-2015-212271. [PMID: 26546623 DOI: 10.1136/bcr-2015-212271] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 68-year-old man diagnosed with cT3N2 adenocarcinoma of the rectum presented with a synchronous solitary liver metastasis on CT scan. Neoadjuvant chemoradiotherapy was started to downstage the primary tumour. Resection of the rectal tumour followed 3 months after the last radiotherapy session and primary resection of the isolated liver lesion was performed in the intervening period. Histopathological assessment of the liver lesion, however, showed no malignancy, but did reveal a necrotic infection due to Enterobius vermicularis. This parasite is frequently found in the intestines, but only rarely infects the liver. The patient was subsequently treated with the anthelmintic drug mebendazole 100 mg once a week for 2 weeks. Histopathological assessment of the rectal specimen showed complete regression after neoadjuvant chemoradiotherapy without evidence of remaining E. vermicularis, suggesting pinworm eradication. The patient recovered promptly after both surgical procedures.
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Affiliation(s)
- Edgar J B Furnée
- Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands
| | - Clothaire Spoto
- Department of Pathology, Diakonessenhuis, Utrecht, The Netherlands
| | - Melanie J de Graaf
- Department of Clinical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Clinical Microbiology, Diakonessenhuis Utrecht, Utrecht, The Netherlands
| | - Niels Smakman
- Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands
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Abstract
The most common malignant causes of biliary strictures are pancreatic cancer and cholangiocarcinoma. Differentiating between malignant and benign causes of biliary strictures has remained a clinical challenge. Endoscopic retrograde cholangiopancreatography (ERCP) remains the mainstay and first-line method of tissue diagnosis but has a poor diagnostic yield. This article reviews the causes of biliary strictures, the initial clinical evaluation of biliary obstruction, the diagnostic yield of ERCP-based sampling methods, the role of newer tools in the armamentarium for evaluating strictures, and ways to address the ongoing challenge of stricture evaluation in patients with primary sclerosing cholangitis.
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Affiliation(s)
- Ming-ming Xu
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA
| | - Amrita Sethi
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA.
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Abstract
Biliary strictures present a diagnostic challenge, especially when no etiology can be ascertained after laboratory evaluation, abdominal imaging and endoscopic retrograde cholangiopancreatography (ERCP) sampling. These strictures were traditionally classified as indeterminate strictures, although with advances in endoscopic techniques and better understanding of hepato-biliary pathology, more are being correctly diagnosed. The implications of missing a malignancy in patients with biliary strictures—and hence delaying surgery—are grave but a significant number of patients (up to 20%) undergoing surgery for suspected biliary malignancy can have benign pathology. The diagnostic approach to these patients involves detailed history and physical examination and depends on the presence or absence of jaundice, level of obstruction, and presence or absence of a mass lesion. While abdominal imaging helps to find the level of obstruction and provides a ‘road map' for further endoscopic investigations, tissue diagnosis is usually needed to make decisions on management. Initially ERCP was the only modality to investigate these strictures but now, with the development of endoscopic ultrasound with fine needle aspiration and the availability of newer techniques such as intraductal ultrasound, single-operator cholangioscopy and confocal laser endomicroscopy, the diagnostic approach to biliary strictures has changed significantly. In this review, we will focus on the decision-making process for patients with biliary strictures and discuss the key decision points that should dictate further diagnostic investigations at each step.
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Affiliation(s)
- Ajaypal Singh
- Center for Endoscopic Research and Therapeutics, Division of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USA and Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine. St. Louis, MO, USA
| | - Andres Gelrud
- Center for Endoscopic Research and Therapeutics, Division of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USA and Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine. St. Louis, MO, USA
| | - Banke Agarwal
- Center for Endoscopic Research and Therapeutics, Division of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USA and Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine. St. Louis, MO, USA
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Schüle S, Altendorf-Hofmann A, Dittmar Y, Rauchfuß F, Settmacher U. [Incidence of non-metastatic liver lesions in tumor patients: consequences for chemotherapy and local ablative procedures]. Chirurg 2014; 85:806-811. [PMID: 24449083 DOI: 10.1007/s00104-013-2660-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Even in patients with a history of solid malignant tumors, especially of gastrointestinal origin, newly diagnosed solid liver lesions do not necessarily correspond to metastases of the respective primary tumor. A reliable diagnosis can only be made by definitive histological examination. MATERIAL AND METHODS Data of all patients who underwent liver resection under the preoperative diagnosis of liver metastases between 1997 and 2011 and for whom liver specimens were examined histologically, were extracted from the prospectively maintained cancer registry. RESULTS An unexpected histological result occurred in 47 out of 770 patients (6.1 %). Primary tumors in these patients included renal cell (n=12), colorectal (n=11), breast (n=8), gastric (n=4), pancreatic (n=3), skin (n=3) and other cancers (n=6). Liver lesions were diagnosed synchronously in 15 cases or metachronously after a median of 17 months following primary therapy in 32 patients. Histology revealed a benign tumor in 38 cases (81 %) as well as 6 cases of HCC, 2 cases of CCC and in 1 case metastasis of a previously unknown colorectal cancer in a patient with known esophageal carcinoma. Suspicion of metastatic disease was based on four different imaging modalities in two cases and on three different imaging modalities in nine cases. Either computed tomography (CT) or magnetic resonance imaging (MRI) was combined with ultrasound in another 23 patients and with positron emission tomography (PET) CT in 6 more cases. In two patients CT plus MRI and CT only, respectively, was performed. In the remaining three patients, suspicion of metastases occurred intraoperatively after macroscopic examination of the liver. Preoperative percutaneous biopsy was attempted in four patients with indeterminate results. CONCLUSION Even with modern diagnostics the risk of treating a benign or other form of malignant tumor with neoadjuvant or palliative chemotherapy persists. The same holds true for local ablative procedures. Prior to local ablation or definitive palliative chemotherapy histological confirmation of metastases should be attempted.
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Affiliation(s)
- S Schüle
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Deutschland,
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Baraniskin A, Nöpel-Dünnebacke S, Schumacher B, Gerges C, Bracht T, Sitek B, Meyer HE, Gerken G, Dechene A, Schlaak JF, Schroers R, Pox C, Schmiegel W, Hahn SA. Analysis of U2 small nuclear RNA fragments in the bile differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders. Dig Dis Sci 2014; 59:1436-41. [PMID: 24482036 DOI: 10.1007/s10620-014-3034-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 01/08/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVES Up to now the diagnosis of early stage cholangiocarcinoma (CC) has remained difficult, with low sensitivities reported for current diagnostic methods. Based on recent promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic and colorectal adenocarcinoma, we studied the utility of RNU2-1f as a diagnostic marker of CC in bile fluid. METHODS Bile fluid was collected from patients with CC (n = 12), controls (patients with choledocholithiasis) (n = 11) and with primary sclerosing cholangitis (PSC; n = 11). RNU2-1f levels were measured by real-time polymerase chain reaction normalized to cel-54. RESULTS Measurement of RNU2-1f levels in bile fluids enabled the differentiation of patients with CC from controls in all cases. Furthermore, RNU2-1f levels in bile fluids of patients with CC were significantly higher than in patients with PSC, resulting in a receiver-operating characteristic curve area of 0.856, with sensitivity of 67 % and specificity of 91 %. CONCLUSIONS Our data suggest that the measurement of RNU2-1 fragments detected in the bile fluid can be used as a diagnostic marker for CC and should be included in future prospective diagnostic studies for this disease entity.
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Affiliation(s)
- Alexander Baraniskin
- Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany,
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Strongin A, Singh H, Eloubeidi MA, Siddiqui AA. Role of endoscopic ultrasonography in the evaluation of extrahepatic cholangiocarcinoma. Endosc Ultrasound 2014; 2:71-6. [PMID: 24949368 PMCID: PMC4062251 DOI: 10.4103/2303-9027.117690] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Accepted: 02/28/2013] [Indexed: 01/04/2023] Open
Abstract
Cholangiocarcinoma is a malignancy that arises from biliary epithelium and is associated with a poor prognosis. Accurate preopera-tive diagnosis and staging of cholangiocarcinoma continues to remain difficult. Endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly performed procedure for cholangiocarcinoma and can provide a tissue diagnosis through brush cytology of the bile duct. However, the sensitivity of biliary brush cytology to diagnose cholangiocarcinoma may be as low as 30%. Endoscopic ultrasound (EUS) is a diagnostic modality which may overcome the limitations of other imaging and biopsy techniques in this setting. EUS can complement the role of ERCP and provide a tissue diagnosis through fine needle aspiration (FNA) and staging through ultrasound imaging. There is currently a paucity of data about the exact role of EUS for the diagnosis of cholan-giocarcinoma in patients with indeterminate extrahepatic biliary strictures. Although multiple studies have shown that EUS is more accurate than ERCP and radiologic imaging for identifying a biliary mass and diagnosing cholangiocarcinoma, the sensitivities are variable. More importantly, the incidence of false negative results is not negligible, though the specificity is close to 100%. There is also controversy regarding the role of EUS-FNA, since even though this may increase diagnosis, it can also lead to tumor seeding.
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Affiliation(s)
- Anna Strongin
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Harkirat Singh
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Mohamad A Eloubeidi
- Division of Gastroenterology, American University of Beirut, Beirut, Lebanon
| | - Ali A Siddiqui
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
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Strongin A, Singh H, Eloubeidi MA, Siddiqui AA. Role of endoscopic ultrasonography in the evaluation of extrahepatic cholangiocarcinoma. Endosc Ultrasound 2014. [PMID: 24949368 DOI: 10.7178/eus.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Cholangiocarcinoma is a malignancy that arises from biliary epithelium and is associated with a poor prognosis. Accurate preopera-tive diagnosis and staging of cholangiocarcinoma continues to remain difficult. Endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly performed procedure for cholangiocarcinoma and can provide a tissue diagnosis through brush cytology of the bile duct. However, the sensitivity of biliary brush cytology to diagnose cholangiocarcinoma may be as low as 30%. Endoscopic ultrasound (EUS) is a diagnostic modality which may overcome the limitations of other imaging and biopsy techniques in this setting. EUS can complement the role of ERCP and provide a tissue diagnosis through fine needle aspiration (FNA) and staging through ultrasound imaging. There is currently a paucity of data about the exact role of EUS for the diagnosis of cholan-giocarcinoma in patients with indeterminate extrahepatic biliary strictures. Although multiple studies have shown that EUS is more accurate than ERCP and radiologic imaging for identifying a biliary mass and diagnosing cholangiocarcinoma, the sensitivities are variable. More importantly, the incidence of false negative results is not negligible, though the specificity is close to 100%. There is also controversy regarding the role of EUS-FNA, since even though this may increase diagnosis, it can also lead to tumor seeding.
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Affiliation(s)
- Anna Strongin
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Harkirat Singh
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Mohamad A Eloubeidi
- Division of Gastroenterology, American University of Beirut, Beirut, Lebanon
| | - Ali A Siddiqui
- Division of Gastroenterology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
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Untereiner V, Sockalingum GD, Garnotel R, Gobinet C, Ramaholimihaso F, Ehrhard F, Diebold MD, Thiéfin G. Bile analysis using high-throughput FTIR spectroscopy for the diagnosis of malignant biliary strictures: a pilot study in 57 patients. JOURNAL OF BIOPHOTONICS 2014; 7:241-253. [PMID: 24677747 DOI: 10.1002/jbio.201300166] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 02/28/2014] [Accepted: 03/04/2014] [Indexed: 06/03/2023]
Abstract
This study aimed at determining whether FTIR spectroscopy is able to distinguish bile samples from patients with and without malignant biliary strictures. Bile samples were collected in 19 patients with malignant biliary strictures and 38 with benign biliary diseases during endoscopic procedures. FTIR spectra were acquired on dried drops of whole bile, aqueous and organic phases obtained after lipid extraction. Data were analyzed by principal component analysis and by the support vector machine classification using a leave-n-out cross validation procedure. This was applied to the whole set of spectra and the mean and median spectra of each patient. By leaving one patient out, the classifier allowed discriminating patients with and without malignant biliary strictures with a sensitivity between 82% and 95% and a specificity between 85% and 100%. Using a randomized leave-n -out cross-validation with n = 2, 5 and 10 patients, the sensitivity decreased slightly by about 5 to 10% while the specificity remained stable, suggesting the robustness of the classifier. FTIR spectroscopy combined with chemometrics therefore shows potential to differentiate bile from patients with and without malignant biliary strictures. Although promising, the results of this pilot study cannot be generalized and needs to be confirmed in a larger population.
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Affiliation(s)
- Valérie Untereiner
- Université de Reims Champagne-Ardenne, MéDIAN-Biophotonique et Technologies pour la Santé, UFR de Pharmacie, 51 rue Cognacq-Jay, 51096 REIMS cedex, France; CNRS UMR7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France
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Sugita R. Magnetic resonance evaluations of biliary malignancy and condition at high-risk for biliary malignancy: Current status. World J Hepatol 2013; 5:654-665. [PMID: 24432183 PMCID: PMC3888665 DOI: 10.4254/wjh.v5.i12.654] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/26/2013] [Accepted: 12/11/2013] [Indexed: 02/06/2023] Open
Abstract
Tumors of the biliary tree are relatively rare; but their incidence is rising worldwide. There are several known risk factors for bile duct cancers, and these are seem to be associated with chronic inflammation of the biliary epithelium. Herein, 2 risk factors have been discussed, primary sclerosing cholangitis and reflux of pancreatic juice into the bile duct, as seen in such as an abnormal union of the pancreatic-biliary junction because magnetic resonance imaging (MRI) is used widely and effectively in the diagnosis of these diseases. When biliary disease is suspected, MRI can often help differentiate between benignity and malignancy, stage tumors, select surgical candidates and guide surgical planning. MRI has many advantages over other modalities. Therefore, MRI is a reliable noninvasive imaging tool for diagnosis and pre-surgical evaluation of bile duct tumors. Nowadays remarkable technical advances in magnetic resonance technology have expanded the clinical applications of MRI in case of biliary diseases. In this article, it is also discussed how recent developments in MRI contributes to the diagnosis of the bile duct cancer and the evaluation of patients with risk factors affecting bile duct cancer.
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The Preoperative Assessment of Hepatic Tumours: Evaluation of UK Regional Multidisciplinary Team Performance. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2013; 2013:861681. [PMID: 24062601 PMCID: PMC3766576 DOI: 10.1155/2013/861681] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 07/18/2013] [Accepted: 07/20/2013] [Indexed: 02/06/2023]
Abstract
Introduction. In the UK, patients where liver resection is contemplated are discussed at hepatobiliary multidisciplinary team (MDT) meetings. The aim was to assess MDT performance by identification of patients where radiological and pathological diagnoses differed. Materials and Methods. A retrospective review of a prospectively maintained database of all cases undergoing liver resection from March 2006 to January 2012 was performed. The presumed diagnosis as a result of radiological investigation and MDT discussion is recorded at the time of surgery. Imaging was reviewed by specialist gastrointestinal radiologists, and resultswereagreedonby consensus. Results. Four hundred and thirty-eight patients were studied. There was a significant increase in the use of preoperative imaging modalities (P ≤ 0.01) but no change in the rate of discrepant diagnosis over time. Forty-two individuals were identified whose final histological diagnosis was different to that following MDT discussion (9.6%). These included 30% of patients diagnosed preoperatively with hepatocellular carcinoma and 25% with cholangiocarcinoma of a major duct. Discussion. MDT assessment of patients preoperatively is accurate in terms of diagnosis. The highest rate of discrepancies occurred in patients with focal lesions without chronic liver disease or primary cancer, where hepatocellular carcinoma was overdiagnosed and peripheral cholangiocarcinoma underdiagnosed, where particular care should be taken. Additional care should be taken in these groups and preoperative multimodality imaging considered.
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