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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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Nardone OM, Iacucci M. Image-Enhanced Endoscopy in the Surveillance of Colitis-Associated Neoplasia. Gastrointest Endosc Clin N Am 2022; 32:845-862. [PMID: 36202520 DOI: 10.1016/j.giec.2022.05.012] [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] [Indexed: 02/04/2023]
Abstract
Advances in endoscopic technology have allowed for improved detection and management of dysplasia. These developments have also raised the question of the optimal methods for surveillance. Promising data showed that virtual chromoendoscopy (VCE) is comparable to dye-based chromoendoscopy (DCE). However, the usefulness of DCE and VCE in the surveillance of longstanding inflammatory bowel disease colitis when compared with high-definition white-light endoscopy has been recently questioned. Confocal laser endomicroscopy is a highly innovative endoscopic procedure but is still far from the routine adoption for surveillance. Thus, a personalized approach should guide the most appropriate surveillance strategy.
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Affiliation(s)
- Olga Maria Nardone
- Institute of Immunology and Immunotherapy, Heritage Building for Research and Development, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TT, United Kingdom.
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, Heritage Building for Research and Development, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TT, United Kingdom.
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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Mi J, Han X, Wang R, Ma R, Zhao D. Diagnostic accuracy of probe-based confocal laser endomicroscopy and tissue sampling by endoscopic retrograde cholangiopancreatography in indeterminate biliary strictures: a meta‑analysis. Sci Rep 2022; 12:7257. [PMID: 35508585 PMCID: PMC9068817 DOI: 10.1038/s41598-022-11385-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 04/22/2022] [Indexed: 11/18/2022] Open
Abstract
Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84-0.91); specificity 0.79 (95% CI 0.74-0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76-38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49-0.59); specificity 0.96 (95% CI 0.94-0.98); and DOR 11.31 (95% CI 3.90-32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts.
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Affiliation(s)
- Junjie Mi
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China.
| | - Xiaofang Han
- Reproductive Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Rong Wang
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
| | - Ruijun Ma
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
| | - Danyu Zhao
- Digestive Endoscopy Center, Shanxi Provincial People's Hospital, No. 29, Shuang ta si Street, Taiyuan, China
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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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Tejaswi S, Loehfelm TW, Olson KA. Cholangioscopy in primary sclerosing cholangitis: a case series of benign features. VideoGIE 2021; 6:431-437. [PMID: 34527845 PMCID: PMC8430051 DOI: 10.1016/j.vgie.2021.05.008] [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] [Indexed: 12/04/2022] Open
Abstract
Background and Aims Cholangioscopy is useful in establishing a visual diagnosis of cholangiocarcinoma (CCA), but this is harder to achieve in primary sclerosing cholangitis (PSC) because of the stricture-forming nature of the disease. Furthermore, it can be harder to differentiate malignant from benign features of the underlying inflammation. This case series demonstrates the varied features of nonmalignant inflammatory findings in PSC. Methods A single experienced endoscopist performed cholangioscopy for PSC cases referred for ERCP. Results Cholangioscopy in these 5 cases without CCA demonstrated the features of acute and chronic inflammation, acute inflammatory mass, dominant stricture, acute cholangitis in a duct with features of chronic inflammation with a large pigmented stone, and fibrostenotic disease. Cholangioscopic maneuvers such as advancement across strictures after balloon dilation, targeted mucosal biopsy, and electrohydraulic lithotripsy (EHL) of impacted stones are demonstrated. The relevant radiographic and histopathologic features of the disease accompany each case description. Regarding long-term prognosis, 1 case of acute inflammatory mass and a case of worsening liver function required a liver transplant evaluation, whereas the other 3 cases remain stable. Conclusions Cholangioscopic features of benign disease in PSC are varied. Knowledge of these features is essential in differentiating between benign and malignant findings. These features, combined with biopsy and cytology evaluation, can help in tailoring management in patients with benign PSC.
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Key Words
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- CBD, common bile duct
- CCA, cholangiocarcinoma
- CHD, common hepatic duct
- EHL, electrohydraulic lithotripsy
- FISH, fluorescent in situ hybridization
- LFTs, liver function tests
- MRI, magnetic resonance imaging
- PSC, primary sclerosing cholangitis
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Affiliation(s)
- Sooraj Tejaswi
- Division of Gastroenterology & Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Thomas W Loehfelm
- Department of Radiology, University of California Davis School of Medicine, Sacramento, California
| | - Kristin A Olson
- Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, California
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7
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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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Han S, Tatman P, Mehrotra S, Wani S, Attwell AR, Edmundowicz SA, Brauer BC, Wagh MS, Hammad HT, Shah RJ. Combination of ERCP-Based Modalities Increases Diagnostic Yield for Biliary Strictures. Dig Dis Sci 2021; 66:1276-1284. [PMID: 32430658 DOI: 10.1007/s10620-020-06335-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 05/08/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Biliary stricture evaluation with brush cytology and intraductal forceps biopsy carries a low sensitivity, but the combination of newer modalities may improve sensitivity. AIM To determine whether the addition of advanced modalities increases diagnostic yield of ERCP-based sampling. METHODS This single-center retrospective study evaluates patients with biliary strictures sampled using brush cytology. Operating characteristics were calculated for individual and combinations of modalities including cholangioscopy, fluoroscopy- and cholangioscopy-directed intraductal biopsy, fluorescence in situ hybridization (FISH), and confocal laser endomicroscopy. Analyses under Standard Criteria (SC) included malignant results as "positive" and Expanded Criteria (EC) included "suspicious" and "high-grade dysplasia" results as "positive." RESULTS A total of 614 patients were included, and 354 (57.8%) received brush cytology alone, which had a sensitivity of 38.5% (SC) to 40.3% (EC) and a specificity of 97.8% (EC) to 99.3% (SC). Combining brush cytology with fluoroscopy-guided biopsy (n = 259, 42.2%) had a sensitivity of 62.5% (SC) to 67.9% (EC) and specificity of 90.2% (EC) to 96.7% (SC). Adding FISH to brush cytology had a sensitivity of 84.2% (SC) to 87.5% (EC) and specificity of 54.1% (SC and EC), while cholangioscopy visualization addition resulted in a sensitivity of 80.4% (SC) to 92.2% (EC) and specificity of 67.3% (EC) to 89.1% (SC). There were no significant differences in sensitivity and specificity using SC and EC. CONCLUSIONS Brush cytology has a low sensitivity, but the addition of other modalities increases sensitivity. There was no difference in specificity between the SC and the EC, supporting the inclusion of "suspicious" impressions with malignant results at our center.
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Affiliation(s)
- Samuel Han
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Philip Tatman
- Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sanjana Mehrotra
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Augustin R Attwell
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Steven A Edmundowicz
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Brian C Brauer
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Mihir S Wagh
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Hazem T Hammad
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA
| | - Raj J Shah
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, Mail Stop F735, 1635 Aurora Ct, Rm. AIP 2.031, Aurora, CO, 80045, USA.
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9
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Abstract
Background and Aims Prompt and accurate differentiation of benign and malignant strictures in primary sclerosing cholangitis (PSC) is crucial. ERCP with brush cytology, the most common modality to achieve this, is hindered by a low diagnostic yield. Cholangioscopy can overcome this limitation by establishing a visual diagnosis based on the characteristic morphologic features of cholangiocarcinoma (CCA) and can aid in targeted biopsies of suspicious lesions. However, its role in PSC remains unclear. This case series demonstrates the performance of the latest generation of single-operator cholangioscope for this indication. Methods A single experienced endoscopist performed cholangioscopy for PSC cases referred for ERCP. Results Cholangioscopies of patients 1 to 3 demonstrate the features of extrahepatic duct dominant strictures (DS) and the cholangioscopic maneuvers undertaken in these cases, including advancement across the DS after balloon dilation, biopsy of the DS, and electrohydraulic lithotripsy of impacted stones. Cholangioscopies of patients 4 to 6 demonstrate the varied features of CCA ranging from focal stricture with tumor vessels, papillary frond-like projections, and features of an intraductal papillary biliary neoplasm. Also shown are the radiographic and histopathologic features of the disease. Conclusions Cholangioscopy allowed us to identify morphologic features of both malignancy and benign disease in PSC in the setting of extrahepatic duct strictures, and we were able to obtain adequate targeted tissue samples for histopathologic confirmation.
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SAGES TAVAC safety and efficacy analysis confocal laser endomicroscopy. Surg Endosc 2020; 35:2091-2103. [PMID: 32405892 DOI: 10.1007/s00464-020-07607-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/28/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Confocal laser endomicroscopy (CLE) is a novel endoscopic adjunct that allows real-time in vivo histological examination of mucosal surfaces. By using intravenous or topical fluorescent agents, CLE highlights certain mucosal elements that facilitate an optical biopsy in real time. CLE technology has been used in different organ systems including the gastrointestinal tract. There has been numerous studies evaluating this technology in gastrointestinal endoscopy, our aim was to evaluate the safety, value, and efficacy of this technology in the gastrointestinal tract. METHODS The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Technology and Value Assessment Committee (TAVAC) performed a PubMed/Medline database search of clinical studies involving CLE in May of 2018. The literature search used combinations of the keywords: confocal laser endomicroscopy, pCLE, Cellvizio, in vivo microscopy, optical histology, advanced endoscopic imaging, and optical diagnosis. Bibliographies of key references were searched for relevant studies not covered by the PubMed search. Case reports and small case series were excluded. The manufacturer's website was also used to identify key references. The United States Food and Drug Administration (U.S. FDA) Manufacturer And User facility and Device Experience (MAUDE) database was searched for reports regarding the device malfunction or injuries. RESULTS The technology offers an excellent safety profile with rare adverse events related to the use of fluorescent agents. It has been shown to increase the detection of dysplastic Barrett's esophagus, gastric intraepithelial neoplasia/early gastric cancer, and dysplasia associated with inflammatory bowel disease when compared to standard screening protocols. It also aids in the differentiation and classification of colorectal polyps, indeterminate biliary strictures, and pancreatic cystic lesions. CONCLUSIONS CLE has an excellent safety profile. CLE can increase the diagnostic accuracy in a number of gastrointestinal pathologies.
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11
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Cholangioscopy Biopsies Improve Detection of Cholangiocarcinoma When Combined with Cytology and FISH, but Not in Patients with PSC. Dig Dis Sci 2020; 65:1471-1478. [PMID: 31571103 DOI: 10.1007/s10620-019-05866-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 09/26/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Single-operator cholangioscopy (SOC) has been suggested to be a cost-effective strategy for the detection of cholangiocarcinoma (CCA). The aim of this study is to compare the performance characteristics of SOC-guided biopsies and transpapillary biopsies with standard sampling techniques for the detection of CCA. METHODS A retrospective cohort study of patients undergoing SOC between 1/2007 and 10/2018 at a single academic center was performed. Demographic, procedural, and outcomes data were recorded and analyzed using STATA 14.0. Sensitivity comparison between diagnostic tests was performed using exact McNemar test exclusively among patients with CCA. Two-sided p value < 0.05 was considered statistically significant. RESULTS Ninety-two patients were included; 36 (39.1%) with primary sclerosing cholangitis (PSC), 41 (44.6%) with CCA, and median follow-up was 15.1 months. In the overall cohort, brush cytology demonstrated a sensitivity of 44.7% and increased with the addition of FISH (56.8%; p = 0.12), FISH with SOC-guided biopsy (71.4%; p = 0.03), and FISH with transpapillary biopsy (64.5%; p = 0.01). However, in patients with PSC, there was no significant improvement in sensitivity with the addition of SOC-guided biopsy or transpapillary biopsy in addition to FISH when compared to brush cytology. There was no difference in the rates of overall adverse events (14% vs. 23.2%; p = 0.27) or infection (3% vs. 4%; p = 0.83) in patients with and without PSC. CONCLUSIONS SOC-guided and transpapillary biopsies improve sensitivity for the detection of cholangiocarcinoma in combination with other ERCP-based techniques compared to brush cytology alone. However, while safe, these modalities do not significantly improve the sensitivity for the detection of malignancy in PSC patients.
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12
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Buchner AM. Confocal Laser Endomicroscopy in the Evaluation of Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:1302-1312. [PMID: 30877772 DOI: 10.1093/ibd/izz021] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, can be effectively monitored with the use of endoscopy. The additional application of small field imaging technology such as confocal laser endomicroscopy CLE during ongoing endoscopic evaluation has led to real-time visualization of mucosal abnormalities and thus in vivo histology. The endomicroscopy (CLE) can improve IBD endoscopic evaluation by identifying seemingly normal-appearing mucosa, assessing the function of the intestinal barrier of the epithelium and vascular permeability, and by characterizing any mucosal lesions, including dysplastic lesions. CLE used during conventional endoscopy could especially facilitate the evaluation of mucosal healing in IBD. In addition, future developments in molecular imaging in IBD may optimize therapeutic approaches by identifying mucosal targets for therapy and determining the reasons for lack of response to specific therapy or subsequent loss of the response.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology at University of Pennsylvania, Philadelphia, Pennsylvania
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13
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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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Marya NB, Tabibian JH. Role of endoscopy in the management of primary sclerosing cholangitis. World J Gastrointest Endosc 2019; 11:84-94. [PMID: 30788027 PMCID: PMC6379747 DOI: 10.4253/wjge.v11.i2.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/15/2019] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent risk for biliary tract and other complications, and the paucity of effective pharmacotherapies, endoscopy plays a major role in the care of many patients with this disorder. In this review, we discuss the endoscopic management of PSC, including established and evolving approaches to the diagnosis and treatment of its benign as well as malignant sequelae. Owing to the rarity of PSC and dearth of high-quality evidence, we propose pragmatic approaches based on both currently available data and expert opinion.
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Affiliation(s)
- Neil Bharat Marya
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Gastroenterology Fellowship Training Program, Los Angeles, CA 90095, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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15
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Ayoub F, Yang D, Draganov PV. Cholangioscopy in the digital era. Transl Gastroenterol Hepatol 2018; 3:82. [PMID: 30505969 DOI: 10.21037/tgh.2018.10.08] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 10/19/2018] [Indexed: 12/16/2022] Open
Abstract
Cholangioscopy allows direct visualization and subsequent therapeutic maneuvers of the biliary ductal system. With advances in endoscopic and imaging technology, cholangioscopy has become an important modality for the diagnosis of indeterminate biliary strictures and an essential therapeutic tool for difficult to remove biliary stones. Enhanced imaging and operability of the latest generation cholangioscopes have further expanded their clinical applications to include ductal tumor ablation, gallbladder drainage, access to difficult to reach branches of the biliary tree, and biliary foreign body manipulation. In this review, we discuss the technical evolution of cholangioscopy into the digital era and review the clinical evidence supporting its use in the diagnosis and therapy of biliary tract disease.
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Affiliation(s)
- Fares Ayoub
- Department of Medicine, Hepatology and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA
| | - Dennis Yang
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA
| | - Peter V Draganov
- Division of Gastroenterology, Hepatology and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA
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Tabibian JH, Baron TH. Endoscopic management of primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol 2018; 12:693-703. [PMID: 29883229 DOI: 10.1080/17474124.2018.1483719] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 05/30/2018] [Indexed: 12/14/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a rare but clinically important cholestatic liver disease. Histopathologically and cholangiographically, PSC is characterized by intra- and/or extra-hepatic bile duct inflammation and fibro-obliteration, which ultimately leads to biliary cirrhosis and related sequelae, including development of hepatobiliary and colorectal carcinomata. PSC can be diagnosed at essentially any age and carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent association with both neoplastic and non-neoplastic biliary tract complications, and the lack of effective pharmacotherapies, alimentary and biliary tract endoscopy plays a major role in the care of patients with PSC. Areas covered: Here, we provide a narrative review on endoscopic management of PSC, including established and evolving applications to the diagnosis and treatment of both its benign and malignant complications. Expert commentary: Due to the rarity of PSC and the considerable patient-years required to rigorously study major endpoints, there remains a paucity of high-quality evidence regarding its management. As the advanced endoscopic repertoire expands, so has the interest in developing best practices in PSC, which we discuss herein.
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Affiliation(s)
- James H Tabibian
- a Division of Gastroenterology, Department of Medicine , Olive View-UCLA Medical Center , Sylmar , CA , USA
| | - Todd H Baron
- b Division of Gastroenterology and Hepatology , University of North Carolina at Chapel Hill , Chapel Hill , NC , USA
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17
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Taghavi SA, Eshraghian A, Niknam R, Sivandzadeh GR, Bagheri Lankarani K. Diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol 2018; 12:575-584. [PMID: 29781738 DOI: 10.1080/17474124.2018.1473761] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 05/02/2018] [Indexed: 02/06/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the hepatobiliary system characterized by chronic inflammation, progressive fibrosis, stricture formation and destruction of extrahepatic and intrahepatic bile ducts. Areas covered: The increased incidence of cholangiocarcinoma (CCA) in PSC has been well documented and can be explained by the continuous inflammation in the biliary tree leading to an enhanced dysplasia-carcinoma sequence. Although PSC patients may progress to liver cirrhosis; CCA most commonly occurs between the ages of 30 and 45 years when cirrhosis has not yet developed. Therefore, CCA in patients with PSC occurs earlier than in patients without PSC. Expert commentary: Despite improvement in diagnostic methods and devices, the dilemma of diagnosing CCA in patients with PSC has not been solved yet and needs further investigation.
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Affiliation(s)
- Seyed Alireza Taghavi
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Ahad Eshraghian
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Ramin Niknam
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Gholam Reza Sivandzadeh
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
| | - Kamran Bagheri Lankarani
- a Gastroenterohepatology Research Center , Shiraz University of Medical Sciences , Shiraz , Iran
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18
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Gao YD, Qu YW, Liu HF. Comparison of diagnostic efficacy between CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures: a meta-analysis. Scand J Gastroenterol 2018. [PMID: 29543078 DOI: 10.1080/00365521.2018.1448435] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The accurate diagnosis of undetermined pancreaticobiliary strictures remains challenging. Current ERCP-guided tissue sampling methods are of low sensitivity. Confocal laser endomicroscopy (CLE) is a new procedure and allows real optical biopsies that may improve the diagnosis of undetermined pancreaticobiliary strictures. The aim of this meta-analysis was to determine the diagnostic yield of CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures. METHOD Pubmed, Embase, and the Cochrane Library database were reviewed for relevant studies. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CIs) were calculated using the random-effects meta-analysis model. The summary receiver-operating characteristic (SROC) curve was constructed, and the area under the receiver operating characteristic curve (AUC) was calculated. RESULTS Twelve studies involving 591 patients were enrolled in our analysis. The overall sensitivity and the specificity estimate of CLE for discriminating benign and malignant pancreaticobiliary strictures were 87% (95%CI, 83-91%) and 76% (95%CI, 70-81%), respectively. The AUC to assess the diagnostic efficacy was 0.8705. For tissue sampling, the overall sensitivity and the specificity estimate were 64% (95%CI, 57-70%) and 94% (95%CI, 90-97%), respectively. The AUC to assess the diagnostic efficacy was 0.8040. A combination of both methods increased the sensitivity (93%; 95%CI, 88-96%) with a specificity of 82% (95%CI, 74-89%). The AUC to assess the diagnostic efficacy was 0.9377. There was no publication bias by Deeks' Funnel Plot with p = .936. CONCLUSIONS Compared with tissue sampling, CLE may increase the sensitivity for the diagnosis of malignant pancreaticobiliary strictures. A combination of both can effectively diagnose malignant pancreaticobiliary strictures.
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Affiliation(s)
- Ya-Dong Gao
- a The Clinical College of the General Hospital of Chinese People's Armed Police Forces, Anhui Medical University , Hefei , China
| | - Ya-Wei Qu
- b Department of Gastroenterology , General Hospital of Chinese People's Armed Police Force , Beijing , China
| | - Hai-Feng Liu
- a The Clinical College of the General Hospital of Chinese People's Armed Police Forces, Anhui Medical University , Hefei , China
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Abstract
Primary sclerosing cholangitis (PSC) remains a rare but potentially devastating chronic, cholestatic liver disease. PSC causes obstruction of intra- and/or extra-hepatic bile ducts by inflammation and fibrosis, leading to biliary obstruction, cirrhosis and portal hypertension with all associated sequelae. The most dreaded consequence of PSC is cholangiocarcinoma, occurring in 10-20% of patients with PSC, and with population-based estimates of a 398-fold increased risk of cholangiocarcinoma in patients with PSC compared to the general population. We use the 4-D approach to endoscopic evaluation and management of PSC based on currently available evidence. After laboratory testing with liver chemistries and high-quality cross-sectional imaging with MRCP, the first D is Dominant stricture diagnosis and evaluation. Second, Dilation of strictures found during ERCP is performed using balloon dilation to as many segments as possible. Third, Dysplasia and cholangiocarcinoma diagnosis is performed by separated brushings for conventional cytology and fluorescence in situ hybridization (FISH), and consideration for direct cholangioscopy with SpyGlass™. Fourt and finally, Dosing of antibiotics is critical to prevent peri-procedural cholangitis. The aim of this review article is to explore endoscopic tools and techniques for the diagnosis and management of PSC and provide a practical approach for clinicians.
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Affiliation(s)
- Jodie A Barkin
- University of Miami, Leonard M. Miller School of Medicine, Department of Medicine, Division of Gastroenterology. Miami, Florida, USA
| | - Cynthia Levy
- University of Miami, Leonard M. Miller School of Medicine, Department of Medicine, Division of Hepatology. Miami, Florida, USA
| | - Enrico O Souto
- University of Miami, Leonard M. Miller School of Medicine, Department of Medicine, Division of Gastroenterology. Miami, Florida, USA
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20
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Papafragkakis C, Lee J. Comprehensive management of cholangiocarcinoma: Part I. Diagnosis. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2017. [DOI: 10.18528/gii1500341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Charilaos Papafragkakis
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey Lee
- epartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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21
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Björnsson ES. Primary sclerosing cholangitis: best practices for diagnosis. Expert Opin Orphan Drugs 2017. [DOI: 10.1080/21678707.2017.1358163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Einar S. Björnsson
- Department of Internal Medicine, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Division of Gastroenterology and Hepatology, The National University Hospital of Iceland
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22
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Asia-Pacific consensus guidelines for endoscopic management of benign biliary strictures. Gastrointest Endosc 2017; 86:44-58. [PMID: 28283322 DOI: 10.1016/j.gie.2017.02.031] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 02/23/2017] [Indexed: 12/11/2022]
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23
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Tatman PD, Osbun J, Yakkioui Y, Kaur S, Parada C, Busald T, Born D, Ahmad O, Zhang J, Ferreira M. Kinase Activity in Recurring Primary Skull Base Chordomas and Chondrosarcomas: Identification of Novel Pathways of Oncogenesis and Potential Drug Targets. World Neurosurg 2017. [PMID: 28647652 DOI: 10.1016/j.wneu.2017.06.106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Chordomas and chondrosarcomas can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within 5 years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the U.S. Food and Drug Administration for chordomas or chondrosarcomas. High propensity for recurrence and lack of definitive adjuvant therapy necessitate additional basic science research to identify molecular anomalies associated with recurrent disease. METHODS We pooled tumor lysates from patients based on clinical criteria into 4 groups: primary chordomas, primary chordomas that recurred, primary chondrosarcomas, and primary chondrosarcomas that recurred. We used a peptide labeling method, isobaric tags for relative and absolute quantitation, to uniquely identify each tumor group. Phosphorylated peptides were identified and quantified via mass spectroscopy to determine and predict active kinases. RESULTS Six groups of phosphorylated peptides were associated with primary tumors that later recurred. Specific kinases associated with primary chordomas that recurred were FES and FER. Specific kinases associated with primary chondrosarcomas that recurred were FES, FER, SRC family kinases, PKC, ROCK, and mitogen-activated protein kinase signaling (JNK, ERK1, p38). CONCLUSIONS These data provide clinicians with a means to screen skull base chordomas and chondrosarcomas to help identify tumors with a propensity to recur. Many of these kinases can be efficaciously inhibited by Food and Drug Administration-approved drugs that have not yet been used in clinical trials for treatment of skull base chordomas or chondrosarcomas. Validation of kinases identified in this study may advance treatment options for patients with these tumors.
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Affiliation(s)
- Philip D Tatman
- Medical Scientist Training Program, University of Colorado, Aurora, Colorado, USA; Department of Neurological Surgery, University of Washington, Seattle, Washington, USA
| | - Joshua Osbun
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA; Department of Neurological Surgery, Emory, Atlanta, Georgia, USA
| | - Youssef Yakkioui
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA; Department of Neurological Surgery, Maastricht University, Maastricht, The Netherlands
| | - Sumanpret Kaur
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA
| | - Carolina Parada
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA
| | - Tina Busald
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA
| | - Donald Born
- Department of Neuropathology, Stanford, California, USA
| | - Owais Ahmad
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA
| | - Jing Zhang
- Department of Neuropathology, University of Washington, Seattle, Washington, USA
| | - Manuel Ferreira
- Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.
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24
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Risk of cholangiocarcinoma in patients with primary sclerosing cholangitis: diagnosis and surveillance. Curr Opin Gastroenterol 2017; 33:78-84. [PMID: 28146445 DOI: 10.1097/mog.0000000000000335] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and extrahepatic malignancy. Particularly the risk of cholangiocarcinoma (CCA) is greatly increased. To provide potentially curative treatments for affected patients an early diagnosis of CCA is crucial. We here review the current advances with respect to CCA diagnosis and surveillance and discuss a rational approach on how to perform surveillance of CCA in PSC patients. RECENT FINDINGS Given the shortcomings of the current modalities for the surveillance and diagnosis of CCA in PSC, recent studies have focused on novel biomarkers for CCA. These include serum biomarkers (e.g., circulating angiopoeitin-2, cytokeratin-19 fragments, and antiglycoprotein 2 IgA autoantibodies, microRNA) as well as proteomics obtained from urine and/or bile. Novel approaches that may enhance the diagnostic value of brush cytology in future include the optimization of fluorescence in situ hybridization probes and the assessment of genetic aberrations. In addition, studies on advanced techniques (e.g., single-operator cholangioscopy and probe-based confocal laser endomicroscopy) have shown promising results with respect to CCA detection. SUMMARY Despite recent advances in the diagnosis of CCA in PSC, the detection of early-stage CCA remains difficult. A better understanding of CCA pathogenesis and large prospective studies on novel biomarkers and techniques are required to timely diagnose CCA in the future.
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25
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Njei B, McCarty TR, Varadarajulu S, Navaneethan U. Systematic review with meta-analysis: endoscopic retrograde cholangiopancreatography-based modalities for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Aliment Pharmacol Ther 2016; 44:1139-1151. [PMID: 27696456 DOI: 10.1111/apt.13817] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 05/18/2016] [Accepted: 09/13/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND The accuracy of current endoscopic modalities for diagnosing cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM To evaluate the comparative effectiveness of endoscopic retrograde cholangiopancreatography (ERCP)-based modalities, independently or in combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced biliary strictures. METHODS Searches of PubMed, EMBASE, Web of Science and the Cochrane Library databases were performed through December 2015. Measured outcomes included sensitivity and specificity of all diagnostic modalities independently or in combination. A bivariate model was used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). A logistic regression model was used to impute the incremental performance of combining two diagnostic tests. RESULTS Twenty-one studies met inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4 on single-operator cholangioscopy with targeted biopsies. Single-operator cholangioscopy with targeted biopsies was the most accurate diagnostic modality at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single-operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341). CONCLUSIONS Single-operator cholangioscopy with targeted biopsies appears to be the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in primary sclerosing cholangitis. However, future large, well-designed comparative diagnostic studies are warranted to validate these findings.
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Affiliation(s)
- B Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.,Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - T R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - S Varadarajulu
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
| | - U Navaneethan
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
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26
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Liu Y, Lu Y, Sun B, Zhang WM, Zhang ZZ, He YP, Yang XJ. Probe-based confocal laser endomicroscopy for the diagnosis of undetermined biliary stenoses: A meta-analysis. Clin Res Hepatol Gastroenterol 2016; 40:666-673. [PMID: 27350572 DOI: 10.1016/j.clinre.2016.05.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 04/14/2016] [Accepted: 05/10/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Presently, both the accuracy and sensitivity for distinguishing biliary stenosis from benign to malignant are low. In recent articles, the probe-based confocal laser endomicroscopy (pCLE) showed a better sensitivity than traditional methods in diagnosing malignant biliary stenosis. Here, we conducted a meta-analysis to summarise the published literature. METHODS A systematic search for literature was conducted in the Medline, Embase and Cochrane Library databases published until November 2015. Further publications were found in the reference lists of the relevant articles. A quality assessment and data extraction were performed by two reviewers independently. A meta-analysis was performed to evaluate the diagnostic efficiency of a pCLE for discriminating benign and malignant biliary stenoses. RESULTS Eight studies involving 280 patients were included in the analysis. Significant heterogeneity in specificity was observed among the studies (Cochran's Q test=15.89, degrees of freedom [df]=7, P=0.0261 and I2=55.9%), while the heterogeneity in sensitivity was not obvious (Cochran's Q test=7.99, df=7, P=0.3334 and I2=12.4%). The area under the summary receiver operating characteristic (SROC) curve was 0.8968. The meta-regression and subgroup analysis indicated that the outlier was the source of heterogeneity. When analysed in the random-effects model, the pooled sensitivity, specificity, positive likelihood ratio (LR) and negative LR were 0.90 (0.84-0.94), 0.75 (0.66-0.83), 3.17 (2.18-4.61) and 0.17 (0.11-0.26), respectively. No significant publication bias was found in our research. CONCLUSION A pCLE is a valuable method for the differential diagnosis between malignant and benign biliary stenoses. However, a preferable diagnostic standard should be explored and improvements in specificity are required.
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Affiliation(s)
- Yuan Liu
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yi Lu
- Digestive Endoscopy Center, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, 197,Ruijin Er Road, Shanghai 200025, China
| | - Bo Sun
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Wen-Ming Zhang
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Zhao-Zhen Zhang
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yi-Ping He
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xiu-Jiang Yang
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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27
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Buchner AM, Wallace MB. Endomicroscopy and Molecular Tools to Evaluate Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2016; 26:657-68. [PMID: 27633594 DOI: 10.1016/j.giec.2016.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Endoscopy is an essential tool for effective care of patients with inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis. The newest endoscopic small-field imaging technologies with confocal endomicroscopy have allowed real-time imaging of gastrointestinal mucosal during ongoing endoscopic evaluation and in vivo histology. Thus, endomicroscopy has a potential to further enhance the endoscopic evaluation of IBD. Advances in molecular in vivo imaging in IBD may be used not only to better understand the pathophysiology of IBD but also to guide optimized therapy and thus to allow a personalized, new approach to the IBD management.
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Affiliation(s)
- Anna M Buchner
- Division of Gastroenterology, University of Pennsylvania, 3400 Civic Center PCAM 7 South, Philadelphia, PA 19104, USA
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
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28
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Risk and Surveillance of Cancers in Primary Biliary Tract Disease. Gastroenterol Res Pract 2016; 2016:3432640. [PMID: 27413366 PMCID: PMC4930812 DOI: 10.1155/2016/3432640] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 04/14/2016] [Accepted: 05/18/2016] [Indexed: 12/20/2022] Open
Abstract
Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases.
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29
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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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30
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Fugazza A, Gaiani F, Carra MC, Brunetti F, Lévy M, Sobhani I, Azoulay D, Catena F, de'Angelis GL, de'Angelis N. Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:4638683. [PMID: 26989684 PMCID: PMC4773527 DOI: 10.1155/2016/4638683] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 12/31/2015] [Indexed: 12/15/2022]
Abstract
Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.
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Affiliation(s)
- Alessandro Fugazza
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Federica Gaiani
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | | | - Francesco Brunetti
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Michaël Lévy
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Iradj Sobhani
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
| | - Daniel Azoulay
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Fausto Catena
- Emergency Surgery Department, University of Parma, 43100 Parma, Italy
| | - Gian Luigi de'Angelis
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Nicola de'Angelis
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
- Department of Advanced Biomedical Sciences, University Federico II of Naples, 80138 Naples, Italy
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Ma HB, Cai LJ, Fan YH. Progress of research and clinical application of probe-based confocal laser endomicroscopy. Shijie Huaren Xiaohua Zazhi 2016; 24:89-96. [DOI: 10.11569/wcjd.v24.i1.89] [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] [Indexed: 02/07/2023] Open
Abstract
Probe based confocal laser endomicroscopy (pCLE) is a new endoscopic diagnostic method which integrates micro-imaging technology into endoscopy and can identify the morphological structure of particular tissue surface, so that the ongoing procedure of endoscopy can make the histopathological diagnosis. pCLE has the "optical biopsy" function, avoids shortcomings in physical biopsies such as being time-consuming, cumbersome, and prone to sampling error, and thus improves the diagnostic accuracy and efficiency. The field of research of pCLE as a new endoscopic imaging technology has been expanded from the digestive cavity structure to the respiratory system and urinary system. This article reviews the progress of research and clinical application of pCLE.
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Probe-Based Confocal Endomicroscopy in Primary Sclerosing Cholangitis: Not All Inflammatory Strictures Are the Same. Dig Dis Sci 2016; 61:283-6. [PMID: 26233552 DOI: 10.1007/s10620-015-3827-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 07/23/2015] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND STUDY AIMS Primary sclerosing cholangitis (PSC) frequently causes inflammatory strictures (IS). The Paris Classification (PC) for probe-based confocal laser endomicroscopy (pCLE) identifies four descriptive criteria of IS. We aim to compare the pCLE findings of IS in PSC and non-PSC patients. PATIENTS AND METHODS This is a single-center, retrospective review of all histologically proven IS evaluated with pCLE with at least 6 months of follow-up. All pCLE images were reviewed for each criteria of the PC: (1) vascular congestion, (2) dark granular pattern, (3) increased inter-glandular space, and (4) thickened reticular structures (TRS). The clinical status (PSC vs. non-PSC) was blinded to the reviewer. Univariate, multivariate, and stepwise logistic regression analyses were conducted. The primary outcome was the number of PC criteria present in PSC versus non-PSC. RESULTS A total of 35 patients (13 PSC, 22 non-PSC) were included (mean age 59.1 years, 25.7 % male). Each of the PC criteria was present more frequently in non-PSC patients. The presence of TRS was significantly different (95 vs. 62 %, p = 0.01). All patients had at least two criteria present, but non-PSC patients had a significantly higher frequency of three criteria (95 vs. 38 %, p < 0.001) and four criteria (55 vs. 23 %, respectively, one-tailed p = 0.03) present. CONCLUSION In patients with IS, the individual and combined components of the PC are present in higher frequency in non-PSC patients. The presence of TRS is 13 times more likely to predict non-PSC etiologies. Refined pCLE criteria may be required to evaluate IS in patients with PSC. CLINICAL TRIAL REGISTRATION NUMBER NCT02166086.
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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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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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Kozarek RA. Single-operator cholangioscopes in the diagnosis of cholangiocarcinoma: seeing is believing. Is belief enough to allow treatment? Gastrointest Endosc 2015; 82:615-617. [PMID: 26385271 DOI: 10.1016/j.gie.2015.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 06/09/2015] [Indexed: 01/03/2023]
Affiliation(s)
- Richard A Kozarek
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
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Tharian B, George NE, Tham TCK. What is the current role of endoscopy in primary sclerosing cholangitis? World J Gastrointest Endosc 2015; 7:920-7. [PMID: 26265986 PMCID: PMC4530326 DOI: 10.4253/wjge.v7.i10.920] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Revised: 03/21/2015] [Accepted: 07/11/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopy has important roles in the management of primary sclerosing cholangitis (PSC), ranging from narrowing down the differential diagnoses, screening for complications, determining prognosis and therapy. While the need for a diagnostic endoscopic retrograde cholangiopancreatography (ERCP) may be obviated by a positive magnetic resonance cholangiopancreatography (MRCP), a negative MRCP does not exclude PSC and may therefore necessitate an ERCP, which is traditionally regarded as the gold standard. In this editorial we have not covered the endoscopic management of inflammatory bowel disease in the context of PSC nor of endoscopic surveillance and treatment of portal hypertension complicating PSC.
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Modha K, Navaneethan U. Diagnosis and management of primary sclerosing cholangitis-perspectives from a therapeutic endoscopist. World J Hepatol 2015; 7:799-805. [PMID: 25914780 PMCID: PMC4404385 DOI: 10.4254/wjh.v7.i5.799] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 01/04/2015] [Accepted: 01/20/2015] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver condition characterized by inflammation, fibrosis, and destruction of the intra- and extrahepatic bile ducts. The therapeutic endoscopist plays a key role in the diagnosis and management of PSC. In patients presenting with a cholestatic profile, endoscopic retrograde cholangiopancreatography (ERCP) is warranted for a definite diagnosis of PSC. Dominant strictures of the bile duct occur in 36%-57% of PSC patients. Endoscopic balloon dilatation with or without stenting have been employed in the management of dominant strictures. In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization forms the initial diagnostic step in the investigation of patients with dominant biliary strictures. Our review aims to summarize the current evidence supporting the role of a therapeutic endoscopist in the management of PSC patients.
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Nanda A, Brown JM, Berger SH, Lewis MM, Barr Fritcher EG, Gores GJ, Keilin SA, Woods KE, Cai Q, Willingham FF. Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma. Therap Adv Gastroenterol 2015; 8:56-65. [PMID: 25729431 PMCID: PMC4314305 DOI: 10.1177/1756283x14564674] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. METHODS In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. RESULTS Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. CONCLUSIONS A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.
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Affiliation(s)
- Arjun Nanda
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Jason M. Brown
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Stephen H. Berger
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Melinda M. Lewis
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Emily G. Barr Fritcher
- Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Steven A. Keilin
- Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Kevin E. Woods
- Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
| | - Qiang Cai
- Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, USA
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Evaluation of pCLE in the bile duct: final results of EMID study : pCLE: impact in the management of bile duct strictures. Surg Endosc 2014; 29:2661-8. [PMID: 25492449 DOI: 10.1007/s00464-014-3986-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 11/04/2014] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Pre-operative histology of bile duct stenosis is associated with low accuracy. Probe confocal laser endomicroscopy (pCLE) enables optical biopsy or in vivo histology. The definitive results of the EMID study are presented here, comparing optical biopsies with definitive histology. AIMS AND METHODS Sixty one patients with a biliary stricture without any previous histology were included (July 2007-May 2012). An endoscopic ultrasound (EUS) had to be conducted before the ERCP procedure. pCLE was done using CholangioFlex during the ERCP procedure. Results were compared to those of definitive histology obtained by biopsy or surgery in case of malignant lesions, and by surgery or 1-year follow-up in case of benign lesions. RESULTS Six patients were excluded because no definitive histology was available. There were 41 malignant lesions and 14 benign lesions. Sensitivity, specificity, PPV, NPV, and accuracy with combination of pCLE with endobiliary and EUS biopsies were 100, 71, 91, 100, and 93%, respectively (with a significant increase of accuracy compared with endobiliary and EUS biopsies without pCLE, p = 0.03). 19 patients had a biliary stricture without individualized mass (6 malignant lesions, 13 benign lesions). Sensitivity, specificity, PPV, NPV, and accuracy for pCLE were 83, 77, 62, 91, and 79%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy for combination of pCLE with endobiliary and EUS biopsies were 100, 69, 60, 100, and 79%, respectively. CONCLUSION The addition of a pCLE procedure in the diagnostic histologic examination of a biliary stricture permits a significant increase in diagnostic reliability and allows for a VPN of 100%.
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Kalaitzakis E, Sturgess R, Kaltsidis H, Oppong K, Lekharaju V, Bergenzaun P, Vlavianos P, Sharma H, Westaby D, Webster GJ. Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis. Scand J Gastroenterol 2014; 49:1237-44. [PMID: 25007715 DOI: 10.3109/00365521.2014.936032] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) in patients with sclerosing cholangitis. METHODS All patients with sclerosing cholangitis who underwent SOC procedures due to suspicious biliary strictures, in one Swedish and four UK tertiary centers in 2008-2012, were retrospectively enrolled. For each SOC procedure in sclerosing cholangitis, another one attempted due to a single biliary stricture in the same center and calendar year was randomly selected as control. Patients were followed up until death or last clinic visit until November 2012. RESULTS Fifty-four SOC procedures were attempted in 52 sclerosing cholangitis patients (48 with primary sclerosing cholangitis, 4 with IgG4-related sclerosing cholangitis). Cannulation with the SOC system failed more frequently in sclerosing cholangitis (15% vs. 2% in controls; p = 0.015). The sensitivity, specificity, and accuracy of SOC (including tissue sampling) for cancer diagnosis were similar in sclerosing cholangitis and controls (50% vs. 55%, 100% vs. 97%, and 88% vs. 80%, respectively) with largely overlapping confidence intervals. Adverse events were more common in sclerosing cholangitis, due to an increased frequency of cholangitis (11% vs. 2% in controls; p = 0.051). CONCLUSIONS SOC is equally accurate in cancer diagnosis in sclerosing cholangitis and patients with single biliary strictures. However, cholangioscope insertion may be hampered by bile duct narrowing and post-SOC cholangitis is more common in sclerosing cholangitis.
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Shah RJ. Cholangiocarcionoma and primary sclerosing cholangitis: the answer lies within. Gastrointest Endosc 2014; 79:780-2. [PMID: 24721627 DOI: 10.1016/j.gie.2013.12.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Accepted: 12/25/2013] [Indexed: 01/28/2023]
Affiliation(s)
- Raj J Shah
- University of Colorado School of Medicine, Aurora, Colorado, USA
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Abstract
PURPOSE OF REVIEW Biliary complications account for relevant morbidity and mortality after liver transplantation. Advances have taken place in understanding their aetiology, in preventive operative techniques, imaging procedures, as well as interventional and endoscopic management. However, progress in living donation, donation after cardiac death as well as paediatric transplant procedures have changed the incidence and causes of biliary complications. This review summarizes recent progress in the field, particularly related to biliary strictures after liver transplantation. RECENT FINDINGS Significant findings in the period of interest for this review focussed on improvements of endoscopic treatment of postliver transplant biliary complications, including novel stenting devices, the routine analysis of bacterial and fungal flora, and the use of steroids to prevent postendoscopic retrograde cholangiopancreaticography pancreatitis. The importance of cytomegalovirus and hepatitis C in the aetiology of biliary complications was highlighted. Under certain circumstances, biliary complications after liver transplantation of organs secondary to donation after cardiac death may be reduced to a level known from liver transplantation after brain death. Further evidence was added to support the risk-adapted use of biliary drainage during liver transplantation. SUMMARY The ongoing research in the aetiology, prevention, and treatment of biliary strictures after liver transplantation highlights the significance of biliary complications for patient and graft outcome.
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Affiliation(s)
- Ryan Law
- From the Division of Gastroenterology and HepatologyMayo ClinicRochesterMN.
| | - Todd H. Baron
- From the Division of Gastroenterology and HepatologyMayo ClinicRochesterMN.
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Modha K, Navaneethan U. Advanced therapeutic endoscopist and inflammatory bowel disease: Dawn of a new role. World J Gastroenterol 2014; 20:3485-3494. [PMID: 24707131 PMCID: PMC3974515 DOI: 10.3748/wjg.v20.i13.3485] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 12/16/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Endoscopy plays a key role in the diagnosis and treatment of patients with inflammatory bowel disease (IBD). Colonoscopy has been traditionally used in the diagnosis of IBD and helps in determination of an important end point in patient management, “mucosal healing”. However, the involvement of an advanced endoscopist has expanded with innovations in therapeutic and newer imaging techniques. Endoscopists are increasingly being involved in the management of anastomotic and small bowel strictures in these patients. The advent of balloon enteroscopy has helped us access areas not deemed possible in the past for dilations. An advanced endoscopist also plays an integral part in managing ileal pouch-anal anastomosis complications including management of pouch strictures and sinuses. The use of rectal endoscopic ultrasound has been expanded for imaging of perianal fistulae in patients with Crohn’s disease and appears much more sensitive than magnetic resonance imaging and exam under anesthesia. Advanced endoscopists also play an integral part in detection of dysplasia by employing advanced imaging techniques. In fact the paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology with pancolonic chromoendoscopy becoming the main imaging modality for neoplasia surveillance in IBD patients in most institutions. Advanced endoscopists are also called upon to diagnose primary sclerosing cholangitis (PSC) and also offer options for endoscopic management of strictures through endoscopic retrograde cholangiopancreatography (ERCP). In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization which assesses the presence of chromosomal aneuploidy (abnormality in chromosome number) are established initial diagnostic techniques in the investigation of patients with biliary strictures. Thus advanced endoscopists play an integral part in the management of IBD patients and our article aims to summarize the current evidence which supports this role and calls for developing and training a new breed of interventionalists who specialize in the management of IBD patients and complications specific to those patients.
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Saadi M, Yu C, Othman MO. A Review of the Challenges Associated with the Diagnosis and Therapy of Primary Sclerosing Cholangitis. J Clin Transl Hepatol 2014; 2:45-52. [PMID: 26357617 PMCID: PMC4548359 DOI: 10.14218/jcth.2013.00021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/01/2014] [Accepted: 02/04/2014] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease that often leads to the development of cirrhosis. Complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, dominant biliary strictures, gallstones, and hepatobiliary malignancies, most commonly cholangiocarcinoma (CCA). Despite the presumed autoimmune etiology of PSC, a clear benefit from immunosuppressive agents has not yet been established, and their use is limited by their side effects. Endoscopy is required in evaluation of biliary strictures in PSC to rule out the possibility of CCA. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease. However, disease recurrence can be a source of morbidity and mortality as transplanted patients survive longer. Further studies are needed to develop an optimal therapeutic strategy for patients with PSC to decrease the incidence of complications of the disease, to decrease the need for transplantation, and to extend life expectancy.
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Affiliation(s)
- Mohammed Saadi
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
| | - Christine Yu
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
| | - Mohamed O Othman
- Department of Medicine, Division of Gastroenterology and Hepatology, Texas Tech University Health Science Center-Paul L. Foster School of Medicine, El Paso, TX, USA
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Abstract
The use of peroral endoscopy in the diagnosis of and therapy for biliary disorders has evolved immensely since the introduction of flexible fiberoptic endoscopes more than 50 years ago. Endoscopic retrograde cholangiopancreatography was introduced approximately a decade after flexible upper endoscopy and has evolved from a purely diagnostic procedure to almost exclusively a therapeutic procedure for managing biliary tract disorders. Endoscopic ultrasound, which continues to be a procedure of high diagnostic yield, is becoming a therapeutic modality for management of biliary diseases. This article discusses the diagnostic and therapeutic aspects of endoscopic retrograde cholangiopancreatography and endoscopic ultrasound for evaluation and treatment of biliary diseases.
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Nakai Y, Isayama H, Shinoura S, Iwashita T, Samarasena JB, Chang KJ, Koike K. Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases. Dig Endosc 2014; 26 Suppl 1:86-94. [PMID: 24033351 DOI: 10.1111/den.12152] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Accepted: 07/02/2013] [Indexed: 12/20/2022]
Abstract
Confocal laser endomicroscopy (CLE) is an emerging diagnostic procedure that enables in vivo pathological evaluation during ongoing endoscopy. There are two types of CLE: endoscope-based CLE (eCLE), which is integrated in the tip of the endoscope, and probe-based CLE (pCLE), which goes through the accessory channel of the endoscope. Clinical data of CLE have been reported mainly in gastrointestinal (GI) diseases including Barrett's esophagus, gastric neoplasms, and colon polyps, but, recently, a smaller pCLE, which goes through a catheter or a fine-needle aspiration needle, was developed and clinical data in the diagnosis of biliary stricture or pancreatic cysts have been increasingly reported. The future application of this novel technique expands beyond the pathological diagnosis to functional or molecular imaging. Despite these promising data, the generalizability of the procedure should be confirmed especially in Japan and other Asian countries, where the current diagnostic yield for GI luminal diseases is high. Given the high cost of CLE devices, cost-benefit analysis should also be considered.
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Affiliation(s)
- Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Palma GDD, Rispo A. Confocal laser endomicroscopy in inflammatory bowel diseases: dream or reality? World J Gastroenterol 2013; 19:5593-5597. [PMID: 24039350 PMCID: PMC3769894 DOI: 10.3748/wjg.v19.i34.5593] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Revised: 06/27/2013] [Accepted: 08/04/2013] [Indexed: 02/06/2023] Open
Abstract
Confocal laser endomicroscopy (CLE) is a newly introduced procedure that provide real-time, high-resolution imaging of the gastrointestinal mucosa during endoscopy, allowing the visualization of the pathology of the mucosal epithelium with its cellular and subcellular structures. Recently, the use of CLE was reported in the study of colonic mucosa in patients with inflammatory bowel diseases and in particular in patients affected by ulcerative colitis. CLE has the potential to have an important role in management of inflammatory bowel diseases (IBD) patients as it can be used to assess the grading of colitis and in detection of microscopic colitis in endoscopically silent segments. Moreover, CLE can be used in surveillance programs especially in high-risk patients. Finally, CLE has been effectively used in diagnosing a biliary dysplasia/neoplasia in patients with primary sclerosing cholangitis, a pathological condition frequently associated with IBD, with a coexisting bile duct stricture.
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