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1
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Cadamuro M, Al-Taee A, Gonda TA. Advanced endoscopy meets molecular diagnosis of cholangiocarcinoma. J Hepatol 2023; 78:1063-1072. [PMID: 36740048 DOI: 10.1016/j.jhep.2023.01.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/22/2022] [Accepted: 01/18/2023] [Indexed: 02/07/2023]
Abstract
Cholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. We present our diagnostic and theranostic approach to the initial evaluation of cholangiocarcinomas, focusing on extrahepatic cholangiocarcinoma. This involves a multipronged strategy incorporating advanced imaging, endoscopic methods, multiple approaches to tissue sampling, and molecular markers. We also provide an algorithm for the sequential use of these tools.
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Affiliation(s)
| | - Ahmad Al-Taee
- Carle Illinois College of Medicine, University of Illinois Urbaba-Champaign, Champaign County, IL, USA
| | - Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University, New York, NY, USA.
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2
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Abstract
Biliary strictures that remain unclassified after cross-sectional imaging and endoscopic retrograde cholangiopancreatography-based tissue sampling are defined as indeterminate biliary strictures (IDBS). A substantial proportion of biliary strictures fall into this category due to low sensitivity of brush cytology and intraductal biopsy. Over last few decades, several modalities have emerged for the evaluation of IDBS. Of these, cholangioscopy and endosonography are the frontrunners and have cemented their place for the evaluation of IDBS. Both of these modalities are widely available, and therefore, biliary strictures that remain uncharacterized after their utilization represent IDBS in the current era.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology & AIG Hospitals, Mind Space Road, Gachibowli, Hyderabad 500 032 India
| | - D Nageshwar Reddy
- Asian Institute of Gastroenterology & AIG Hospitals, Mind Space Road, Gachibowli, Hyderabad 500 032 India.
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3
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Kim DH, Krishna SG, Coronel E, Kröner PT, Wolfsen HC, Wallace MB, Corral JE. Confocal Laser Endomicroscopy in the Diagnosis of Biliary and Pancreatic Disorders: A Systematic Analysis. Clin Endosc 2022; 55:197-207. [PMID: 34839621 PMCID: PMC8995979 DOI: 10.5946/ce.2021.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/15/2021] [Accepted: 05/10/2021] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND/AIMS Endoscopic visualization of the microscopic anatomy can facilitate the real-time diagnosis of pancreatobiliary disorders and provide guidance for treatment. This study aimed to review the technique, image classification, and diagnostic performance of confocal laser endomicroscopy (CLE). METHODS We conducted a systematic review of CLE in pancreatic and biliary ducts of humans, and have provided a narrative of the technique, image classification, diagnostic performance, ongoing research, and limitations. RESULTS Probe-based CLE differentiates malignant from benign biliary strictures (sensitivity, ≥89%; specificity, ≥61%). Needlebased CLE differentiates mucinous from non-mucinous pancreatic cysts (sensitivity, 59%; specificity, ≥94%) and identifies dysplasia. Pancreatitis may develop in 2-7% of pancreatic cyst cases. Needle-based CLE has potential applications in adenocarcinoma, neuroendocrine tumors, and pancreatitis (chronic or autoimmune). Costs, catheter lifespan, endoscopist training, and interobserver variability are challenges for routine utilization. CONCLUSION CLE reveals microscopic pancreatobiliary system anatomy with adequate specificity and sensitivity. Reducing costs and simplifying image interpretation will promote utilization by advanced endoscopists.
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Affiliation(s)
- Do Han Kim
- Universidad Francisco Marroquin, School of Medicine, Guatemala City, Guatemala
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Emmanuel Coronel
- Division of Gastroenterology and Hepatology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Paul T. Kröner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Herbert C. Wolfsen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael B. Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Juan E. Corral
- Division of Gastroenterology and Hepatology, Presbyterian Health Services, Albuquerque, New Mexico, USA
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4
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Abstract
Indeterminate biliary strictures are defined as a narrowing of the bile duct that cannot be differentiated as malignant or benign after performing cross-sectional imaging and an ERCP. Identifying the etiology of a bile duct stricture is the single most important step in determining whether a complex and potentially morbid surgical resection is warranted. Due to this diagnostic and therapeutic dilemma, new technologies, laboratory tests, and procedures are emerging to solve this problem.
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5
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Han S, Kahaleh M, Sharaiha RZ, Tarnasky PR, Kedia P, Slivka A, Chennat JS, Joshi V, Sejpal DV, Sethi A, Shah RJ. Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial. Gastrointest Endosc 2021; 94:569-576.e1. [PMID: 33798541 DOI: 10.1016/j.gie.2021.03.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/21/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures. METHODS This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer. RESULTS Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9). CONCLUSIONS In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michel Kahaleh
- Division of Gastroenterology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA
| | - Reem Z Sharaiha
- Division of Gastroenterology, Weill Cornell Medical Center, New York, New York, USA
| | - Paul R Tarnasky
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Prashant Kedia
- Division of Gastroenterology, Dallas Methodist Medical Center, Dallas, Texas, USA
| | - Adam Slivka
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer S Chennat
- Division of Gastroenterology and Hepatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Virendra Joshi
- Division of Gastroenterology, Louisiana State University Health Center, New Orleans, Louisiana, USA
| | - Divyesh V Sejpal
- Division of Gastroenterology, Northwell Health, Manhasset, New York, USA
| | - Amrita Sethi
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | - Raj J Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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6
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Benson M, Pfau P. Probe-based confocal laser endoscopy and primary sclerosing cholangitis: Is seeing actually believing? Gastrointest Endosc 2021; 94:577-579. [PMID: 34412828 DOI: 10.1016/j.gie.2021.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Mark Benson
- Section of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Patrick Pfau
- Section of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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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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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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Thomaidis T, Kallimanis G, May G, Zhou P, Sivanathan V, Mosko J, Triantafillidis JK, Teshima C, Moehler M. Advances in the endoscopic management of malignant biliary obstruction. Ann Gastroenterol 2020; 33:338-347. [PMID: 32624653 PMCID: PMC7315700 DOI: 10.20524/aog.2020.0497] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022] Open
Abstract
Biliary obstruction is common in pancreatobiliary malignancies and has a negative impact on the patient's quality of life, postoperative complications, and survival rates. Particularly in the last decade, there has been enormous progress regarding the diagnostic and therapeutic options in patients with malignant biliary obstruction. Endoscopy has given a new insight in this direction and novel techniques have been developed for the better characterization and treatment of malignant strictures. We herein summarize the available data on the different endoscopic techniques, and clarify their role in the diagnosis and treatment of malignant biliary obstructive disease. Finally, we propose an algorithm that can facilitate management decisions in these patients.
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Affiliation(s)
- Thomas Thomaidis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - George Kallimanis
- 2 Gastroenterology Clinic, Hygeia Hospital, Athens, Greece (Thomas Thomaidis, George Kallimanis)
| | - Gary May
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Pinghong Zhou
- Interventional endoscopy, Zhongshan Hospital, Fudan University, Shanghai, China (Pinghong Zhou)
| | - Visvakanth Sivanathan
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
| | - Jeff Mosko
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | | | - Christopher Teshima
- Division of Therapeutic Endoscopy, St. Michael’s Hospital, University of Toronto, Toronto, Canada (Gary May, Jeff Mosko, Christopher Teshima)
| | - Markus Moehler
- Johannes Gutenberg University, Mainz, Germany (Thomas Thomaidis, Visvakanth Sivanathan, Markus Moehler)
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10
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Nakai Y, Isayama H, Wang H, Rerknimitr R, Khor C, Yasuda I, Kogure H, Moon JH, Lau J, Lakhtakia S, Ratanachu‐ek T, Seo DW, Lee DK, Makmun D, Dy F, Liao W, Draganov PV, Almadi M, Irisawa A, Katanuma A, Kitano M, Ryozawa S, Fujisawa T, Wallace MB, Itoi T, Devereaux B. International consensus statements for endoscopic management of distal biliary stricture. J Gastroenterol Hepatol 2020; 35:967-979. [PMID: 31802537 PMCID: PMC7318125 DOI: 10.1111/jgh.14955] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 12/01/2019] [Accepted: 12/02/2019] [Indexed: 02/05/2023]
Abstract
Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico-biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato-biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS.
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Affiliation(s)
- Yousuke Nakai
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
- Department of Endoscopy and Endoscopic Surgery, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
- Department of Gastroenterology, Graduate School of MedicineJuntendo UniversityTokyoJapan
| | - Hsiu‐Po Wang
- Department of Internal Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of MedicineChulalongkorn UniversityBangkokThailand
| | - Christopher Khor
- Department of Gastroenterology and HepatologySingapore General Hospital and Duke‐NUS Medical SchoolSingaporeSingapore
| | - Ichiro Yasuda
- Third Department of Internal Medicine, Graduate School of MedicineUniversity of ToyamaToyamaJapan
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Jong Ho Moon
- Digestive Disease Center and Research Institute, Department of Internal MedicineSoonChunHyang University School of MedicineBucheon/SeoulSouth Korea
| | - James Lau
- Department of Surgery, Endoscopic Center, Prince of Wales HospitalThe Chinese University of Hong KongHong Kong, China
| | | | | | - Dong Wan Seo
- Department of Internal MedicineUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulSouth Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Gangnam Severance HospitalYonsei University College of MedicineSeoulSouth Korea
| | - Dadang Makmun
- Division of Gastroenterology, Department of Internal Medicine, Faculty of MedicineUniversitas Indonesia/Cipto Mangunkusumo National General HospitalJakartaIndonesia
| | - Frederick Dy
- Section of Gastroenterology, Department of Internal Medicine, Faculty of Medicine and SurgeryUniversity of Santo Tomas HospitalManilaPhilippines
| | - Wei‐Chih Liao
- Department of Internal Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan
| | - Peter V Draganov
- Department of MedicineUniversity of FloridaGainesvilleFloridaUSA
| | - Majid Almadi
- Division of Gastroenterology, King Khalid University HospitalKing Saud UniversityRiyadhSaudi Arabia
| | - Atsushi Irisawa
- Department of GastroenterologyDokkyo Medical UniversityTochigiJapan
| | - Akio Katanuma
- Center for GastroenterologyTeine‐Keijinkai HospitalSapporoJapan
| | - Masayuki Kitano
- Second Department of Internal MedicineWakayama Medical UniversityWakayamaJapan
| | - Shomei Ryozawa
- Department of GastroenterologySaitama Medical University International Medical CenterSaitamaJapan
| | - Toshio Fujisawa
- Department of Gastroenterology, Graduate School of MedicineJuntendo UniversityTokyoJapan
| | | | - Takao Itoi
- Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyoJapan
| | - Benedict Devereaux
- University of QueenslandRoyal Brisbane and Women's HospitalBrisbaneQueenslandAustralia
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11
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Liu TC, VanBuskirk K, Ali SA, Kelly MP, Holtz LR, Yilmaz OH, Sadiq K, Iqbal N, Amadi B, Syed S, Ahmed T, Moore S, Ndao IM, Isaacs MH, Pfeifer JD, Atlas H, Tarr PI, Denno DM, Moskaluk CA. A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth. PLoS Negl Trop Dis 2020; 14:e0007975. [PMID: 31929525 PMCID: PMC6980693 DOI: 10.1371/journal.pntd.0007975] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 01/24/2020] [Accepted: 12/06/2019] [Indexed: 02/06/2023] Open
Abstract
Background A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. Methods Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. Results Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet’s AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort. Conclusions We propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world. The study of EED has been limited by the lack of a rigorously tested, reproducible histology index that can provide insight to the pathogenesis of this entity. In this study we report the first duodenal histology index that was developed using an unbiased approach, with excellent inter-observer reproducibility, for the study of EED. The EED histology index readily identified histologic features that are common or unique to cohorts of distinct geographic locations. Incorporating the histology index into future clinical studies will provide useful insight into the pathogenesis and for intervention strategy development.
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Affiliation(s)
- Ta-Chiang Liu
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Kelley VanBuskirk
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Syed A. Ali
- Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - M. Paul Kelly
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
- Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom
| | - Lori R. Holtz
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Omer H. Yilmaz
- The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, Department of Pathology, Massachusetts General Hospital, Boston, MA, United States of America
| | - Kamran Sadiq
- Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Najeeha Iqbal
- Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Beatrice Amadi
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Sana Syed
- Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan
- Department of Pediatrics, University of Virginia, Charlottesville, VA, United States of America
| | - Tahmeed Ahmed
- Nutrition and Clinical Services Division (NCSD), International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- James P. Grant School of Public Health, BRAC University, Dhaka, Bangladesh
| | - Sean Moore
- Department of Pediatrics, University of Virginia, Charlottesville, VA, United States of America
| | - I. Malick Ndao
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Michael H. Isaacs
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America
| | - John D. Pfeifer
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Hannah Atlas
- Departments of Pediatrics and Global Health, University of Washington, Seattle, WA, United States of America
| | - Phillip I. Tarr
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States of America
| | - Donna M. Denno
- Departments of Pediatrics and Global Health, University of Washington, Seattle, WA, United States of America
| | - Christopher A. Moskaluk
- Department of Pathology, University of Virginia, Charlottesville, VA, United States of America
- * E-mail:
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12
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Dubow M, Tatman PD, Shah RJ. Individual probe based confocal laser endomicroscopy criteria in the analysis of indeterminate biliary strictures. Scand J Gastroenterol 2019; 53:1358-1363. [PMID: 30394137 DOI: 10.1080/00365521.2018.1512151] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Evaluation of indeterminate biliary strictures remains challenging due to limited sensitivity of endoscopic tissue sampling. Biliary probe-based confocal laser endomicroscopy (pCLE) has shown promise to detect and exclude neoplasia. However, knowledge of whether individual inflammatory criteria are more prevalent in neoplasia compared to benign strictures is limited. The objective of this work is to improve diagnosis of neoplastic and inflammatory conditions using pCLE. MATERIALS AND METHODS The charts of all patients who underwent pCLE at a single referral center between 2009 and 2015 were reviewed. ERCP reports were reviewed for eleven Miami and Paris criteria. Primary outcome was the identification of neoplasia by histopathology (defined as high-grade dysplasia and/or adenocarcinoma). To model predictors of neoplasia, we fit a binary regression model incorporating data from pCLE operating criteria, pCLE impression, and PSC status. RESULTS 97 patients were identified. In the 27 patients with neoplasia, there was increasing number of Miami malignant criteria (Pearson r = 0.512, p < .001) while inflammatory criteria were less prevalent. 10% (5/51, p < .001) of patients with benign pCLE impression developed neoplasia, while 48% (22/46, p < .001) with suspicious pCLE impressions developed neoplasia. The binary regression model to predict neoplasia had a sensitivity of 83.3%, specificity of 92.5%, and overall accuracy 89.7%. CONCLUSIONS Presence of malignant criteria and absence of certain inflammatory criteria are more prevalent in patients with neoplasia. Our model, which weights individual imaging components, shows impressive sensitivity and specificity over prior prognostic efforts. Prospective studies will be required to evaluate this model.
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Affiliation(s)
- Michael Dubow
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA
| | - Philip D Tatman
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA.,b Medical Scientist Training Program , University of Colorado , Aurora , CO , USA
| | - Raj J Shah
- a Department of Medicine, Division of Gastroenterology , University of Colorado , Aurora , CO , USA
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13
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Abstract
Benign and malignant biliary strictures are common indications for endoscopic retrograde cholangiopancreatography. Diagnosis involves high-quality cross-sectional imaging and cholangiography with various endoscopic sampling techniques. Treatment options include placement of plastic biliary stents and self-expanding metal stents, which differ in patency duration and cost effectiveness. Whether the etiology is benign or malignant, a multidisciplinary strategy should be implemented. This article will discuss general principles of biliary stenting in both benign and malignant conditions.
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Affiliation(s)
- Jason G Bill
- Washington University School of Medicine in St. Louis, 660 South Euclid Avenue, Campus Box 8124, St Louis, MO 63110, USA
| | - Daniel K Mullady
- Interventional Endoscopy, Washington University School of Medicine in St. Louis, 660 South Euclid Avenue, Campus Box 8124, St Louis, MO 63110, USA.
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14
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Novikov A, Kowalski TE, Loren DE. Practical Management of Indeterminate Biliary Strictures. Gastrointest Endosc Clin N Am 2019; 29:205-214. [PMID: 30846149 DOI: 10.1016/j.giec.2018.12.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Indeterminate biliary strictures pose a diagnostic and therapeutic challenge. Although underlying malignancy is a primary concern, biliary strictures may result from benign processes. An accurate diagnosis is paramount to define the treatment strategy and minimize morbidity. The limitations of traditional endoscopic retrograde cholangiopancreatography-based tissue acquisition with cytology brushings are well-documented. Endoscopic retrograde cholangiopancreatography is generally unable to determine a stricture's etiology. Complementary advanced endoscopic imaging and multimodal tissue acquisition have evolved. Careful consideration of the clinical presentation, location of the stricture, and interpretation of imaging constitute the most optimal approach for diagnosis and management.
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Affiliation(s)
- Aleksey Novikov
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA
| | - Thomas E Kowalski
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA
| | - David E Loren
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, 132 South 10th Street, 585 Main Building, Philadelphia, PA 19107, USA.
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15
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Sun B, Moon JH, Cai Q, Rerknimitr R, Ma S, Lakhtakia S, Ryozawa S, Kutsumi H, Yasuda I, Shiomi H, Li X, Li W, Zhang X, Itoi T, Wang HP, Qian D, Wong Lau JY, Yang Z, Ji M, Hu B. Review article: Asia-Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures. Aliment Pharmacol Ther 2018; 48:138-151. [PMID: 29876948 DOI: 10.1111/apt.14811] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Revised: 03/23/2018] [Accepted: 04/26/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pre-operative tissue diagnosis for suspected malignant biliary strictures remains challenging. AIM To develop evidence-based consensus statements on endoscopic tissue acquisition for biliary strictures. METHODS The initial draft of statements was prepared following a systematic literature review. A committee of 20 experts from Asia-Pacific region then reviewed, discussed, and modified the statements. Two rounds of independent voting were conducted to reach a final version. Consensus was considered to be achieved when 80% or more of voting members voted "agree completely" or "agree with some reservation." RESULTS Eleven statements achieved consensus. The choice of tissue sampling modalities for biliary strictures depends on the clinical setting, the location of lesion, and availability of expertise. Detailed radiological and endoscopic evaluation is useful to guide the selection of appropriate tissue acquisition technique. Standard intraductal biliary brushing and/or forceps biopsy is the first option when endoscopic biliary drainage is required with an overall (range) sensitivity and specificity of 45% (26%-72%) and 99% (98%-100%), and 48% (15%-100%) and 99% (97%-100%), respectively, in diagnosing malignant biliary strictures. Probe-based confocal laser endomicroscopy and fluorescence in situ hybridisation using 4 fluorescent-labelled probes targeting chromosomes 3, 7, 17 and 9p21 locus may be added to improve the diagnostic yield. Cholangioscopy-guided biopsy and EUS-guided tissue acquisition can be considered after prior negative conventional tissue sampling with an overall (range) sensitivity and specificity of 60% (38%-88%) and 98% (83%-100%), and 80% (46%-100%) and 97% (92%-100%), respectively, in diagnosing malignant biliary strictures. CONCLUSION These consensus statements provide evidence-based recommendations for endoscopic tissue acquisition of biliary strictures.
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16
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Rizvi S, Eaton J, Yang JD, Chandrasekhara V, Gores GJ. Emerging Technologies for the Diagnosis of Perihilar Cholangiocarcinoma. Semin Liver Dis 2018; 38:160-169. [PMID: 29871021 PMCID: PMC6463495 DOI: 10.1055/s-0038-1655775] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Such technologies include enhanced visualization of the biliary tree by cholangioscopy, intraductal ultrasound, and confocal laser endomicroscopy. Conventional cytology can be aided by employing complementary and advanced cytologic techniques such as fluorescent in situ hybridization (FISH), and this technique should be widely adapted. Interrogation of bile and serum by examining extracellular vesicle number and cargo, and exploiting next-generation sequencing and proteomic technologies, is also being explored. Examination of circulating cell-free deoxyribonucleic acid (cfDNA) for differentially methylated regions is a promising test which is being rigorously validated. The special expertise required for these analyses has to date hampered their validation and adaptation. Herein, we will review these emerging technologies to inform the reader of the progress made and encourage further studies, as well as adaptation of validated approaches.
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Affiliation(s)
- Sumera Rizvi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John Eaton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ju Dong Yang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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17
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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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18
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Reid MD, Lewis MM, Willingham FF, Adsay NV. The Evolving Role of Pathology in New Developments, Classification, Terminology, and Diagnosis of Pancreatobiliary Neoplasms. Arch Pathol Lab Med 2017; 141:366-380. [PMID: 28055239 DOI: 10.5858/arpa.2016-0262-sa] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Pancreatobiliary tract lesions are increasingly being discovered because of more sensitive imaging modalities. Magnetic resonance imaging has identified incidental pancreatic cysts in 13.5% of patients of progressively increasing age. Pancreatobiliary tissue is more accessible through endoscopic ultrasound and magnetic resonance imaging-guided biopsy procedures, and is now an integral part of pathologists' routine practice. Accordingly, several new tumor categories have been recently recognized, including intraductal tubulopapillary neoplasm, a new addition to tumoral intraepithelial neoplasms. Other entities have been reclassified, including the recent transition to 2-tiered grading of preinvasive neoplasms, as well as new perspectives on the distinctive biologic behavior of oncocytic intraductal papillary mucinous neoplasms (IPMNs) compared with other IPMN subtypes. This has led to proposals for revised staging of virtually every segment of the pancreatobiliary tree, with theranostic markers becoming an integral part of workup. Ki-67 is now an integral part of the classification of neuroendocrine tumors, with new definitions of "high-grade neuroendocrine carcinoma." Although bile duct brushings have opened new avenues for diagnosis, their sensitivity remains low and often requires concomitant fluorescent in situ hybridization to better define ambiguous cases. Various molecular pathways have been elucidated for pancreatic cysts, including KRAS for ductal neoplasia, GNAS for intestinal IPMNs, RNF3 for mucinous cysts, and VHL for serous cystic neoplasms, all key players in diagnostic workup. Integration of these updates into our understanding of pancreatobiliary disease requires active engagement of pathologists for appropriate specimen triage, judicious interpretation of results, and incorporation into reporting and staging. They also provide exciting opportunities for targeted therapy.
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Affiliation(s)
| | | | | | - N Volkan Adsay
- From the Departments of Pathology (Drs Reid, Lewis, and Adsay) and Digestive Diseases (Dr Willingham), Emory University School of Medicine, Atlanta, Georgia
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19
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Dawwas MF, Oppong KW, Webster GJ. Endoscopic assessment and management of biliary strictures. Frontline Gastroenterol 2016; 7:170-175. [PMID: 28839854 PMCID: PMC5369516 DOI: 10.1136/flgastro-2015-100570] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 05/20/2015] [Indexed: 02/04/2023] Open
Affiliation(s)
- M F Dawwas
- Division of Digestive Diseases and Nutrition, Department of Medicine, University of Kentucky Medical Center, Lexington, Kentucky, USA,Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne, UK
| | - K W Oppong
- Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne, UK
| | - G J Webster
- Department of Gastroenterology, University College Hospital, London, UK
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20
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Is Seeing Really Believing? Probe-based Confocal Laser Endomicroscopy in the Evaluation of Pancreaticobiliary Disease. J Clin Gastroenterol 2016; 50:359-65. [PMID: 26927493 DOI: 10.1097/mcg.0000000000000505] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Confocal laser endomicroscopy for real-time diagnosis during endoscopic procedures has now been in the mainstream clinical arena for a decade. Indeterminate biliary strictures and pancreatic cysts remain 2 difficult diagnostic challenges for the gastroenterologist, and the role this technology will play in the approach to these problems is still evolving. There is now a body of literature to guide the endoscopist in the use of this imaging tool, including how it may be useful in excluding biliary malignancy, and how miniaturization has allowed for endoscopic ultrasound-guided application of the probe within cysts. Interobserver variability remains a weakness of the system. Tips for use of this tool and interpretation of the imaging data it provides are discussed.
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21
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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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22
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Abstract
The evaluation of pancreatic lesions, from solid pancreatic masses to pancreatic cysts, remains a clinical challenge. Although cross-sectional imaging remains the cornerstone of the initial evaluation of an indeterminate pancreatic lesion, advances in imaging with the advent of endoscopic ultrasound scan, elastography, contrast-enhanced endoscopic ultrasound scan, and probe-based confocal laser endomicroscopy have allowed us to visualize the pancreas in even higher resolution and diagnose premalignant and malignant lesions of the pancreas with improved accuracy. This report reviews the range of imaging tools currently available to evaluate pancreatic lesions, from solid tumors to pancreatic cysts.
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Affiliation(s)
- Ming-ming Xu
- Division of Digestive and Liver Disease, Columbia University Medical Center, 622 West 168th Street, New York, NY 10032, USA
| | - Amrita Sethi
- Division of Digestive and Liver Disease, Columbia University Medical Center, 622 West 168th Street, New York, NY 10032, USA.
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23
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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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24
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Tabibian JH, Visrodia KH, Levy MJ, Gostout CJ. Advanced endoscopic imaging of indeterminate biliary strictures. World J Gastrointest Endosc 2015; 7:1268-1278. [PMID: 26675379 PMCID: PMC4673389 DOI: 10.4253/wjge.v7.i18.1268] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 08/05/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs.
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25
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Almadi MA, Neumann H. Probe based confocal laser endomicroscopy of the pancreatobiliary system. World J Gastroenterol 2015; 21:12696-708. [PMID: 26640347 PMCID: PMC4658625 DOI: 10.3748/wjg.v21.i44.12696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 07/08/2015] [Accepted: 09/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To review applications of confocal laser endomicroscopy (CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to pCLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and cross-referencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies. RESULTS In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of (98% vs 45%) and has a negative predictive value (97% vs 69%), but decreased the specificity (67% vs 100%) and the positive predictive value (71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of pCLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation. CONCLUSION The role of pCLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.
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26
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Moore C, Mehta V, Ma X, Chaudhery S, Shi R, Moore-Medlin T, Lian T, Nathan CAO. Interobserver agreement of confocal laser endomicroscopy for detection of head and neck neoplasia. Laryngoscope 2015; 126:632-7. [DOI: 10.1002/lary.25646] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2015] [Indexed: 01/17/2023]
Affiliation(s)
- Charles Moore
- Louisiana State University Health Shreveport School of Medicine; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Vikas Mehta
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Xiaohui Ma
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Shabnum Chaudhery
- Louisiana State University Health Shreveport School of Medicine; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Department of Pathology; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Runhua Shi
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Tara Moore-Medlin
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Timothy Lian
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Cherie-Ann O. Nathan
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
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27
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Abstract
Benign biliary strictures are a common indication for endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has evolved over the last 2 decades as the current standard of care. The most common etiologies of strictures encountered are following surgery and those related to chronic pancreatitis. High-quality cross-sectional imaging provides a road map for endoscopic management. Currently, sequential placement of multiple plastic biliary stents represents the preferred approach. There is an increasing role for the treatment of these strictures using covered metal stents, but due to conflicting reports of efficacies as well as cost and complications, this approach should only be entertained following careful consideration. Optimal management of strictures is best achieved using a team approach with the surgeon and interventional radiologist playing an important role.
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28
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29
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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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30
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Talreja JP, Turner BG, Gress FG, Ho S, Sarkaria S, Paddu N, Natov N, Bharmal S, Gaidhane M, Sethi A, Kahaleh M. Pre- and post-training session evaluation for interobserver agreement and diagnostic accuracy of probe-based confocal laser endomicroscopy for biliary strictures. Dig Endosc 2014; 26:577-80. [PMID: 24344750 DOI: 10.1111/den.12214] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Accepted: 11/08/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Current diagnostic modalities for indeterminate biliary strictures offer low accuracy. Probe-based confocal laser endomicroscopy (pCLE) permits microscopic assessment of mucosal structures by obtaining real-time high-resolution images of the mucosal layers of the gastrointestinal tract. Previously, an interobserver study demonstrated poor to fair agreement even among experienced confocal endomicroscopy operators. Our objective was to assess interobserver agreement and diagnostic accuracy upon completion of a pCLE training session. METHODS Forty de-identified pCLE video clips of indeterminate biliary strictures were sent to five endoscopists at four tertiary care centers for scoring. Observers subsequently attended a teaching session by an expert pCLE user that included 20 training clips and rescored the same pCLE video clips, which were randomized and renumbered. RESULTS Pre-training interobserver agreement for all observers was 'fair' (Κ: 0.31, P-value: <0.0001) and diagnostic accuracy was 72% (55-80%). Post-training interobserver agreement for all observers was 'substantial' (Κ: 0.74, P-value: <0.0001) and diagnostic accuracy was 89% (80-95%). Using a paired t-test, we observed an increase of 17% (95% CI 7.6-26.4) in post-training diagnostic accuracy (t = 5.01, df = 4, P-value 0.007). CONCLUSIONS Interobserver agreement and diagnostic accuracy improved after observers underwent training by an expert pCLE user with a specific sequence set. Users should participate in such training programs to maximize diagnostic accuracy of pCLE evaluation.
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Affiliation(s)
- Jayant P Talreja
- Department of Gastroenterology, University of Virginia, Charlottesville, USA
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31
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Abstract
Performing real-time microscopy has been a vision of endoscopists since the very early phases of gastrointestinal endoscopy. Confocal endomicroscopy, an adaption of confocal laser scanning microscopy, and endocytoscopy, an adaption of white-light microscopy, have been introduced into the endoscopic armamentarium in the past decade. Both techniques yield on-site histological information. Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract, and also the hepatobiliary-pancreatic system, during endoscopy. Such microscopic information has been successfully used in expert hands to minimize sampling error by 'smart', microscopically targeted biopsies and to guide endoscopic interventions. However, endomicroscopy is also unique in its ability to dynamically visualize cellular processes in their native environment free of artefacts. This ability enables fundamental insights into mechanisms of human diseases in clinical and translational science.
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32
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Abstract
Differentiating between malignant and benign bile duct strictures is often challenging. Endoscopic retrograde cholangiopancreatography with brush cytology and/or endobiliary forceps biopsy is routinely performed. Advanced cytologic methods such as fluorescence in situ hybridization or digital image analysis increases the sensitivity of cytology. Endoscopic ultrasonography enables detailed examination of tissues surrounding the bile duct stricture and offers the advantage of fine-needle aspiration. Intraductal ultrasonography enables detailed evaluation of bile duct wall layers, and cholangioscopy offers direct visualization of the bile duct lesions. Novel techniques of probe-based confocal laser endomicroscopy and optical coherence tomography have introduced the era of in vivo histology.
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Affiliation(s)
- Won Jae Yoon
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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Peter S, Bang JY, Mönkemuller K, Varardarajulu S, Wilcox CM. Endomicroscopy of the pancreaticobiliary system. DIAGNOSTIC AND THERAPEUTIC ENDOSCOPY 2013; 2013:310105. [PMID: 23476111 PMCID: PMC3586466 DOI: 10.1155/2013/310105] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 01/02/2013] [Indexed: 02/07/2023]
Abstract
It is often difficult to accurately differentiate between benign and malignant pancreaticobiliary strictures, and some are interpreted as indeterminate despite ERCP, EUS, or radiological imaging techniques, thereby making it difficult for the clinician to make appropriate management decisions. Probe-based confocal laser endomicroscopy (pCLE) is an innovative imaging tool integrating real-time in vivo imaging of these difficult-to-interpret strictures in the pancreaticobiliary system during endoscopy. Recent studies of endomicroscopy have shown a promising role with improved accuracy in distinguishing these lesions, thus paving the way for future research addressing improving precise interpretation, training, and long long-term impact.
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Affiliation(s)
| | | | | | | | - C. Mel Wilcox
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL 35294-0012, USA
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Kalaitzakis E. Establishing a diagnosis in indeterminate pancreaticobiliary strictures: is confocal laser endomicroscopy the answer? Dig Dis Sci 2012; 57:3052-4. [PMID: 22996791 DOI: 10.1007/s10620-012-2389-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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