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Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, Myrelid P. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2024; 18:1556-1582. [PMID: 38878002 DOI: 10.1093/ecco-jcc/jjae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Abstract
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | | | | | - Maria Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Giuseppe S Sica
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | | | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gordon William Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | | | | | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - João Guedelha Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | | | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | - Pierre Ellu
- Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
| | - Alaa El-Hussuna
- OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King's College London, London, UK
| | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | | | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hannah Gordon
- Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Alpha-1 Antitrypsin Inhibits Tumorigenesis and Progression of Colitis-Associated Colon Cancer through Suppression of Inflammatory Neutrophil-Activated Serine Proteases and IGFBP-3 Proteolysis. Int J Mol Sci 2022; 23:ijms232213737. [PMID: 36430216 PMCID: PMC9698049 DOI: 10.3390/ijms232213737] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 10/31/2022] [Accepted: 11/04/2022] [Indexed: 11/11/2022] Open
Abstract
Colitis-associated colon cancer (CAC) accompanies the massive infiltration of neutrophils during tumorigenesis and progression of CAC. Depletion of neutrophils in circulation results in significant inhibition of tumor incidence in CAC. However, the underlying mechanisms are largely unclear. In this study, we provide evidence for the crucial involvement of inflammatory neutrophil-activated serine proteases (NSPs) on the dysregulation of the anti-inflammatory and antitumor IGFBP-3/IGFBP-3R signaling axis in CAC using a chronic AOM/DSS mouse model. We also provide preclinical evidence for α1-antitrypsin (AAT) as a preventive and as a therapeutic for CAC. AAT administration not only prevented colitis-associated tumorigenesis but also inhibited established CAC. AOM/DSS treatment results in the significant activation of NSPs, leading to CAC through increased pro-inflammatory cytokines and decreased anti-inflammatory and antitumor IGFBP-3. Collectively, these data suggest that the NSPs proteolyze IGFBP-3, whereas AAT inhibits chronic colonic inflammation-induced NSP activity and subsequently suppresses IGFBP-3 proteolysis. Therefore, the anti-inflammatory and antitumor functions of the IGFBP-3/IGFBP-3R axis are restored. AAT mimicking small peptides also showed their inhibitory effects on NSP-induced IGFBP-3 proteolysis. These results suggest that targeting the NSP-IGFBP-3/IGFBP-3R axis using NSP inhibitors such as AAT and the AAT mimics and IGFBP-3R agonists could lead to novel approaches for the prevention and treatment of CAC.
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Lerner DG, Mencin A, Novak I, Huang C, Ng K, Lirio RA, Khlevner J, Utterson EC, Harris BR, Pitman RT, Mir S, Gugig R, Walsh CM, Fishman D. Advances in Pediatric Diagnostic Endoscopy: A State-of-the-Art Review. JPGN REPORTS 2022; 3:e224. [PMID: 37168622 PMCID: PMC10158303 DOI: 10.1097/pg9.0000000000000224] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 04/20/2022] [Indexed: 05/13/2023]
Abstract
Pediatric endoscopy has revolutionized the way we diagnose and treat gastrointestinal disorders in children. Technological advances in computer processing and imaging continue to affect endoscopic equipment and advance diagnostic tools for pediatric endoscopy. Although commonly used by adult gastroenterologists, modalities, such as endomicroscopy, image-enhanced endoscopy, and impedance planimetry, are not routinely used in pediatric gastroenterology. This state-of-the-art review describes advances in diagnostic modalities, including image-enhanced endoscopy, confocal laser endomicroscopy, optical coherence tomography, endo functional luminal imaging probes, wireless motility/pH capsule, wireless colon capsule endoscopy, endoscopic ultrasound, and discusses the basic principles of each technology, including adult indications and pediatric applications, safety cost, and training data.
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Affiliation(s)
- Diana G. Lerner
- From the Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI
| | - Ali Mencin
- Division of Pediatric Gastroenterology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Inna Novak
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children’s Hospital at Montefiore, Bronx, NY
| | - Clifton Huang
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cook Children’s Medical Center, Fort Worth, TX
| | - Kenneth Ng
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Richard A. Lirio
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, UMASS Memorial Children’s Medical Center/UMASS Medical School, Worcester, MA
| | - Julie Khlevner
- Division of Pediatric Gastroenterology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Elizabeth C. Utterson
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO
| | - Brendan R. Harris
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO
| | - Ryan T. Pitman
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, MO
| | - Sabina Mir
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, UNC School of Medicine, Chapel Hill, NC
| | - Roberto Gugig
- Lucile Packard Children’s Hospital at Stanford, Palo Alto, CA
| | - Catharine M. Walsh
- Department of Paediatrics and the Wilson Centre, Division of Gastroenterology, Hepatology and Nutrition and the Research and Learning Institutes, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Doug Fishman
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX
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Efficacy and Safety of Endoscopic Submucosal Dissection for Dysplasia in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2022; 2022:9556161. [PMID: 35126511 PMCID: PMC8808217 DOI: 10.1155/2022/9556161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 11/11/2021] [Accepted: 11/12/2021] [Indexed: 02/07/2023] Open
Abstract
Background and Aims. Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer. Current guidelines recommend endoscopic resection if the lesion is visible with distinct margins and a complete resection can be achieved. However, submucosal fibrosis due to chronic inflammation may increase the procedural risk and reduce the complete resection rate. The aim of this study is to assess the efficacy and safety of endoscopic submucosal dissection (ESD) for dysplasia in UC patients. Materials and Methods. A systematic search of databases was performed until May 30, 2021. Studies that reported the resection rates and complication rates of ESD for dysplasia in UC patients were included. A random-effects model was used to generate conservative estimates of the prevalence of the outcome variables. All data analyses were performed using software Stata (version 15). Results. 8 studies were enrolled in the meta-analysis, with a total of 203 dysplastic lesions in 192 UC patients. The mean lesion size was 26.7 mm. About 83% of the lesions were located in the left-side colon, and 90% of the lesions were nonpolypoid, and about 71% of the lesions had submucosal fibrosis. The mean procedural time of ESD was 83 minutes. The en bloc resection rate, complete resection rate, and curative resection rate were 94%, 84%, and 81%, respectively, with a local recurrence rate of 5%. The pooled prevalence of bleeding and perforation were 8% and 6%, respectively. The rates of metachronous tumors and additional surgery after ESD were 6% and 10%, respectively. Conclusion. Despite some limitations, our study suggests that ESD is an effective and safe treatment for dysplasia in UC patients. However, randomized controlled multicenter studies with less heterogeneity and longer follow-up are needed to better assess the clinical outcomes of ESD in UC patients.
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Georgakopoulou E, Evangelou K, Gorgoulis VG. Premalignant lesions and cellular senescence. CELLULAR SENESCENCE IN DISEASE 2022:29-60. [DOI: 10.1016/b978-0-12-822514-1.00001-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Challenges in Crohn's Disease Management after Gastrointestinal Cancer Diagnosis. Cancers (Basel) 2021; 13:cancers13030574. [PMID: 33540674 PMCID: PMC7867285 DOI: 10.3390/cancers13030574] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/25/2021] [Accepted: 01/29/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Crohn’s disease (CD) is a chronic inflammatory bowel disease affecting both young and elderly patients, involving the entire gastrointestinal tract from the mouth to anus. The chronic transmural inflammation can lead to several complications, among which gastrointestinal cancers represent one of the most life-threatening, with a higher risk of onset as compared to the general population. Moreover, diagnostic and therapeutic strategies in this subset of patients still represent a significant challenge for physicians. Thus, the aim of this review is to provide a comprehensive overview of the current evidence for an adequate diagnostic pathway and medical and surgical management of CD patients after gastrointestinal cancer onset. Abstract Crohn’s disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.
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Manta R, Zullo A, Telesca DA, Castellani D, Germani U, Reggiani Bonetti L, Conigliaro R, Galloro G. Endoscopic Submucosal Dissection for Visible Dysplasia Treatment in Ulcerative Colitis Patients: Cases Series and Systematic Review of Literature. J Crohns Colitis 2021; 15:165-168. [PMID: 32710744 DOI: 10.1093/ecco-jcc/jjaa158] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Ulcerative colitis [UC] patients are at an increased risk of developing colorectal cancer due to chronic inflammation. Endoscopic submucosal dissection [ESD] allows removal of non-invasive neoplastic lesions in the colon, but few data are available on its efficacy in UC patients. METHODS Data from consecutive UC patients diagnosed with visible dysplastic lesions in the colon who underwent ESD were evaluated. The en bloc removal, R0 resection and complication rates were calculated. Local recurrence and metachronous lesions during follow-up were identified. A systematic review of the literature with pooled data analysis was performed. RESULTS A total of 53 UC patients [age: 65 years; range 30-74; M/F: 31/22] underwent ESD. The en bloc resection rate was 100%, and the R0 resection rate was 96.2%. Bleeding occurred in seven [13.2%] patients, and perforation in three [5.6%] cases, all treated at endoscopy. No recurrence was observed, but two metachronous lesions were detected. Data from six other studies [three Asian and three European] were available. By pooling data, en bloc resection was successful in 88.4% (95% confidence interval [CI] = 83.5-92) of 216 lesions and in 91.8% [95% CI = 87.3-94.8] of 208 patients. R0 resection was achieved in 169 ESDs, equivalent to a 78.2% [95% CI = 72.3-83.2] rate for lesions and 81.3% [95% CI = 75.4-86] rate for patients. No difference between European and Asian series was noted. CONCLUSIONS This pooled data analysis indicated that ESD is a suitable tool for safely and properly removing non-invasive neoplastic lesions on colonic mucosa of selected UC patients.
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Affiliation(s)
- Raffaele Manta
- Gastroenterology and Digestive Endoscopy Unit, General Hospital of Perugia, Italy
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | | | - Danilo Castellani
- Gastroenterology and Digestive Endoscopy Unit, General Hospital of Perugia, Italy
| | - Ugo Germani
- Gastroenterology and Digestive Endoscopy Unit, General Hospital of Perugia, Italy
| | - Luca Reggiani Bonetti
- Department of Diagnostic Medicine and Public Health, University of Modena and Reggio Emilia Section of Pathology, Modena, Italy
| | - Rita Conigliaro
- Gastroenterology and Digestive Endoscopy Unit, S. Agostino-Estense Hospital, Modena, Italy
| | - Giuseppe Galloro
- Surgical Digestive Endoscopy, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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Pathologist Experience and Concordance in the Diagnosis of Dysplasia in Long-standing Inflammatory Bowel Disease. Am J Surg Pathol 2020; 44:955-961. [PMID: 32235151 DOI: 10.1097/pas.0000000000001475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Surveillance colonoscopies focused to detect dysplasia are recommended to prevent colorectal cancer in patients with long-standing colonic inflammatory bowel disease (IBD). To date, histologic diagnosis and gradation of IBD-related dysplasia has been challenged by a high variability among pathologists. We aimed to analyze the observer characteristics that are correlated with concordance deviations in this diagnosis. Eight pathologists evaluated a set of 125 endoscopic biopsy samples with a representative distribution of nondysplastic and dysplastic lesions from long-standing IBD patients. Two rounds of diagnosis were carried out during a period of 18 months. The κ test was applied to analyze concordance. Pathologists were grouped on the basis of their experience. A subanalysis was performed by eliminating the highly prevalent nondysplastic samples, as well as an analysis after observers' grouping. Overall interobserver agreement was good (κ=0.73), with an even higher pairwise value (κ=0.86) as well as the intraobserver agreement values (best κ=0.85). After eliminating the highly prevalent nondysplastic samples, the interobserver agreement was still moderate to good (best overall κ=0.50; best paired κ=0.72). Notable differences were seen between the pathologists with a high-volume and low-volume practice (best overall κ=0.61 and 0.41, respectively). The agreement in the diagnosis of dysplasia in IBD endoscopic biopsies may have been undervalued over time. This is the first study evaluating pathologists' diagnostic robustness in this field. The results suggest that examining a large volume of samples is the key factor to increase the consistency in the diagnosis and gradation of IBD-related dysplasia.
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Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions. Cancers (Basel) 2020; 12:cancers12082018. [PMID: 32718028 PMCID: PMC7463640 DOI: 10.3390/cancers12082018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance.
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Villanacci V, Reggiani-Bonetti L, Caprioli F, Saragoni L, Salviato T, Mescoli C, Canavese G, Manenti S, Spada E, Baron L, Leoncini G, Cadei M, Battista S, Armuzzi A. Histopathology of inflammatory bowel disease - Position statement of the Pathologists of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC). Dig Liver Dis 2020; 52:262-267. [PMID: 31884010 DOI: 10.1016/j.dld.2019.11.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 10/27/2019] [Accepted: 11/08/2019] [Indexed: 12/11/2022]
Abstract
Diagnosis of the inflammatory bowel diseases ulcerative colitis (UC) and Crohn's disease (CD) relies mainly on the histopathological examination of endoscopic biopsies of the gastrointestinal tract. To facilitate the accurate diagnosis of these two conditions, this paper addresses key issues on the: (A) gastrointestinal biopsy procedure, (B) histomorphological characteristics of UC and CD, and (C) diagnosis of dysplasia. The 13 statements presented here represent the consensus of two groups of Italian pathologists (IG-IBD and GIPAD).
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Affiliation(s)
| | - Luca Reggiani-Bonetti
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, and Department of Pathophysiology, Department of Transplantation, University of Milan, Milan, Italy
| | - Luca Saragoni
- Department of Pathological Anatomy, AUSL Romagna, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Tiziana Salviato
- Department of Diagnostic, Clinic and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Claudia Mescoli
- Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova, Padua, Italy
| | - Gabriella Canavese
- Pathology Department, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy
| | | | | | - Luigi Baron
- Pathology Unit, St. Leonardo Hospital, Castellammare di Stabia, Naples, Italy
| | - Giuseppe Leoncini
- Pathology Unit, ASST del Garda, Desenzano del Garda (BS), Brescia, Italy
| | - Moris Cadei
- Institute of Pathology, ASST Spedali Civili, Brescia, Italy
| | - Serena Battista
- Institute of Pathology Azienda Ospedaliera Universitaria Integrata, Udine, Italy
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy
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Severo RF, do Amaral CC, Garcia TF, Ferrúa CP, Corrêa GP, Klug AB, da Silva KD, Bastos CR, Britto Correa M, Ghisleni GC, Uchoa Vasconcelos AC, Tarquinio SBC, Nedel F. The T102C polymorphism of 5HT2A receptor in oral epithelial dysplasia: A pilot case-control study. Arch Oral Biol 2020; 113:104688. [PMID: 32146149 DOI: 10.1016/j.archoralbio.2020.104688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 01/14/2020] [Accepted: 02/21/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVE investigate the T102C polymorphism of 5HT2A receptor in dysplasia in oral potentially malignant lesions and its association with smoking and alcohol habits. METHODS case-control study that included patients with oral potentially malignant lesions (OPML) histopathologically diagnosed with dysplasia and healthy controls, and within these group patients with and without smoking and alcohol consumption habits. Cell samples from the oral lesions were collected with the patients previously anesthetized using disposable cytological brushes. Deoxyribonucleic acid (DNA) extraction was performed and the T102C polymorphism (rs6313) was genotyped in a real-time polymerase chain reaction (PCR) allelic discrimination assays. RESULTS 110 individuals were included in this study (38 with dysplasia and 72 controls). The genotype (p = 0.016), allele (p = 0.020) and smoking habits (<0.001) distribution differed significantly between dysplasia and control group, where the CT and TT (C - cytosine/ T - thymine) genotype and the T allele showed a higher frequency in dysplasia (65.6, 18.8 and 84.4 %, respectively) than in controls (55.7, 4.9 and 60.7). Concerning smoking habits, the higher frequency was in the dysplasia group. The multivariate logistic regression analysis, associating variables of interest and the presence of dysplasia, showed that individuals with smoking habits present 7.58 increase risk to develop dysplasia than non-smokers; and individuals carrying the T allele for the T102C polymorphism have a 4.6 increased risk to develop oral dysplasia in OPML. CONCLUSIONS the T102C polymorphism is associated with oral dysplasia in OPML, however, failed to show association with smoking and alcohol habits in OPML dysplasia.
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Affiliation(s)
- Rafaely Ferreira Severo
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Cainá Corrêa do Amaral
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Tiago Fernandez Garcia
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Camila Perelló Ferrúa
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Geovanna Peter Corrêa
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Adriana Beiersdorff Klug
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Karine Duarte da Silva
- Graduate Program in Dentistry of the Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil
| | - Clarissa Ribeiro Bastos
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil
| | - Marcos Britto Correa
- Graduate Program in Dentistry of the Federal University of Pelotas, Pelotas, RS, 96010-610, Brazil
| | | | | | | | - Fernanda Nedel
- Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, 96010-901, Brazil.
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12
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Kotsafti A, D'Incà R, Scarpa M, Fassan M, Angriman I, Mescoli C, Bortoli N, Brun P, Bardini R, Rugge M, Savarino E, Zingone F, Castoro C, Castagliuolo I, Scarpa M. Weak Cytotoxic T Cells Activation Predicts Low-Grade Dysplasia Persistence in Ulcerative Colitis. Clin Transl Gastroenterol 2019; 10:e00061. [PMID: 31343468 PMCID: PMC6708661 DOI: 10.14309/ctg.0000000000000061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 05/16/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION In patients with ulcerative colitis (UC), dysplasia develops in 10%-20% of cases. The persistence of low-grade dysplasia (LGD) in UC in 2 consecutive observations is still an indication for restorative proctocolectomy. Our hypothesis is that in the case of weak cytotoxic activation, dysplasia persists. We aimed to identify possible immunological markers of LGD presence and persistence. METHODS We prospectively enrolled 112 UC patients who underwent screening colonoscopy (T0) who had biopsies taken from their sigmoid colon. Ninety of them had at least a second colonoscopy (T1) with biopsies taken in the sigmoid colon and 8 patients had dysplasia in both examinations suggesting a persistence of LGD in their colon. Immunohistochemistry and real time polymerase chain reaction for CD4, CD69, CD107, and CD8β messenger RNA (mRNA) expression and flow cytometry for epithelial cells expressing CD80 or HLA avidin-biotin complex were performed. Non-parametric statistics, receiver operating characteristic curves analysis, and logistic multiple regression analysis were used. RESULTS Thirteen patients had LGD diagnosed at T0. The mucosal mRNA expression of CD4, CD69, and CD8β was significantly lower than in patients without dysplasia (P = 0.033, P = 0.046 and P = 0.007, respectively). A second colonoscopy was performed in 90 patients after a median follow-up of 17 (12-25) months and 14 of the patients were diagnosed with LGD. In these patients, CD8β mRNA expression at T0 was significantly lower in patients without dysplasia (P = 0.004). A multivariate survival analysis in a model including CD8β mRNA levels and age >50 demonstrated that both items were independent predictors of dysplasia at follow-up (hazard ratio [HR] = 0.47 [95% confidence interval [CI]: 0.26-0.86], P = 0.014, and HR = 13.32 [95% CI: 1.72-102.92], P = 0.013). DISCUSSION These data suggest a low cytotoxic T cell activation in the colonic mucosa of UC patients who do not manage to clear dysplasia. Thus, low level of CD8β mRNA expression in non-dysplastic colonic mucosa might be considered in future studies about the decision making of management of LGD in UC.
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MESH Headings
- Adult
- Antigens, CD/metabolism
- Antigens, Differentiation, T-Lymphocyte/metabolism
- B7-1 Antigen/metabolism
- Biopsy
- CD4 Antigens/metabolism
- CD8 Antigens/metabolism
- Colitis, Ulcerative/diagnostic imaging
- Colitis, Ulcerative/pathology
- Colon, Sigmoid/pathology
- Colonoscopy/methods
- Female
- Humans
- Hyperplasia/classification
- Hyperplasia/pathology
- Immunohistochemistry/instrumentation
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/pathology
- Lectins, C-Type/metabolism
- Lysosomal-Associated Membrane Protein 1/metabolism
- Lysosomal-Associated Membrane Protein 2/metabolism
- Male
- Middle Aged
- Proctocolectomy, Restorative/standards
- Prospective Studies
- RNA, Messenger/metabolism
- Survival Analysis
- T-Lymphocytes, Cytotoxic/metabolism
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Affiliation(s)
- Andromachi Kotsafti
- Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
| | - Renata D'Incà
- Gastroenterology Unit, Azienda Ospedaliera di Padova, Padova, Italy
| | - Melania Scarpa
- Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
| | - Matteo Fassan
- Department of Medicine, University of Padova, Padova, Italy
| | - Imerio Angriman
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | - Nicolò Bortoli
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Paola Brun
- Department of Molecular Medicine, University of Padova, Padova, Italy
| | - Romeo Bardini
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medicine, University of Padova, Padova, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Carlo Castoro
- Upper GI Surgery Unit, Istituto Humanitas, Rozzano, Italy
| | | | - Marco Scarpa
- General Surgery Unit, Azienda Ospedaliera di Padova, Padova, Italy
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13
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Kim ES, Kim KO, Jang BI, Kim EY, Lee YJ, Lee HS, Jeon SW, Kim HJ, Kim SK. Comparison of 4-L Polyethylene Glycol and 2-L Polyethylene Glycol Plus Ascorbic Acid in Patients with Inactive Ulcerative Colitis. Dig Dis Sci 2017. [PMID: 28639128 DOI: 10.1007/s10620-017-4634-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although colonoscopy preparation may cause symptom flares in patients with ulcerative colitis (UC), little is known about the standard preparation regimen in this population. AIM We aimed to compare 4L polyethylene glycol (4L-PEG) with 2L polyethylene glycol plus ascorbic acid (2L-PEG-Asc) in quiescent UC patients. METHODS Patients with inactive UC undergoing colonoscopy for surveillance or checkup of mucosal healing were prospectively enrolled at 5 tertiary hospitals. They were randomly assigned to 4L-PEG and 2L-PEG-Asc groups. The Boston Bowel Preparation Scale (BBPS) was used for the preparation quality. Symptoms were assessed using the Simple Clinical Colitis Activity Index (SCCAI) before colonoscopy, at 1 and 4 weeks after the procedure. RESULTS Overall, 109 patients were included in the study (4L-PEG group 53, 2L-PEG-Asc group 56, the mean age at diagnosis 42.25 years, male 77). The quality of preparation was comparable between the groups (BBPS ≥ 6, 96.2 vs. 92.9%, p = 0.679). Although 26 patients (23.8%) had increased SCCAI scores within 4 weeks after colonoscopy, resulting in a medication dose-up or add-on in 3 patients (2.7%), the rise in scores was not different between the groups. No serious adverse events during preparation were observed in either group. However, the 2L-PEG-Asc group was more likely to be willing to repeat the preparation with the same agent than the 4L-PEG group (82.1 vs. 64.2%, respectively, p = 0.034). CONCLUSION PEG-based regimens with different volumes are equally effective and safe in inactive UC patients. 2L-PEG-Asc is more acceptable in this population as indicated by the willingness for further usage.
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Affiliation(s)
- Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea
| | - Kyeong Ok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Byung Ik Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Eun Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Yoo Jin Lee
- Division of Gastroenterology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyun Seok Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea
| | - Seong Woo Jeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea
| | - Hyun Jin Kim
- Division of Gastroenterology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Changwon, Korea
| | - Sung Kook Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea.
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14
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Saraggi D, Fassan M, Mescoli C, Scarpa M, Valeri N, Michielan A, D'Incá R, Rugge M. The molecular landscape of colitis-associated carcinogenesis. Dig Liver Dis 2017; 49:326-330. [PMID: 28089111 DOI: 10.1016/j.dld.2016.12.011] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 12/07/2016] [Accepted: 12/09/2016] [Indexed: 12/11/2022]
Abstract
In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapies.
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Affiliation(s)
- Deborah Saraggi
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Claudia Mescoli
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy
| | - Marco Scarpa
- Istituto Oncologico Veneto, IOV-IRCCS, Surgical Oncology Unit, Padua, Italy
| | - Nicola Valeri
- Department of Molecular Pathology, The Institute of Cancer Research, London, UK; Department of Medicine, The Royal Marsden NHS Trust, London, UK
| | - Andrea Michielan
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy
| | - Renata D'Incá
- Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
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15
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Santos SCDD, Barbosa LER. Crohn's disease: risk factor for colorectal cancer. JOURNAL OF COLOPROCTOLOGY 2017. [DOI: 10.1016/j.jcol.2016.06.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/11/2023]
Abstract
Abstract
Background Crohn's disease is an inflammatory disease that can reach any part of the gastrointestinal tract. This disease has been associated with an increased neoplastic risk, including colorectal carcinoma.
Objective The objective of this work is to describe the mechanisms present in two diseases, and that are responsible for the increased risk in Crohn's disease.
Methods A bibliographic research was conducted in PubMed database. In addition to the articles obtained with an inserted query in Pubmed, other references relevant to the topic in question were included.
Results Colorectal cancer risk varies according to the presence of certain factors, and an example of this is Crohn's disease. Chronic inflammation seems to be an important contribution to carcinogenesis, since it creates a microenvironment suitable for the onset and progression of the disease. There are molecular changes that are common to two conditions, thus justifying the fact of Crohn's disease being a risk factor for colorectal carcinoma. The disease control with an appropriate therapy and with surveillance are two ways to control this risk.
Conclusions A proinflammatory state is the cornerstone in the association between Crohn's disease and colorectal carcinoma. The implementation of surveillance strategies allowed a decrease in morbidity and mortality associated with this cancer.
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Affiliation(s)
| | - Laura Elisabete Ribeiro Barbosa
- Universidade do Porto, Faculdade de Medicina, Porto, Portugal
- Hospital de São João, Serviço de Cirurgia Geral, Porto, Portugal
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16
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Dlugosz A, Barakat AM, Björkström NK, Öst Å, Bergquist A. Diagnostic yield of endomicroscopy for dysplasia in primary sclerosing cholangitis associated inflammatory bowel disease: a feasibility study. Endosc Int Open 2016; 4:E901-11. [PMID: 27540581 PMCID: PMC4988862 DOI: 10.1055/s-0042-111203] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Accepted: 06/13/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD) is characterized by a high risk of colorectal dysplasia. Surveillance colonoscopies with random biopsies have doubtful power for dysplasia detection. Our aim was to prospectively investigate the feasibility and efficacy of pCLE in surveillance colonoscopies in patients with PSC-IBD. PATIENTS AND METHODS Sixty-nine patients with PSC-IBD underwent colonoscopy in 2 steps. On the way from rectum to cecum, the mucosa was inspected with high definition endoscopy (HDE) and random biopsies were taken according to the standard routine. On the way from cecum to rectum, fluorescein-enhanced pCLE and chromoendoscopy were performed. Regions where random biopsies had been taken, as well as visible lesions, were examined with pCLE and targeted biopsies were taken of lesions suspicious for dysplasia. Two investigators, blinded to histology and endoscopy results, analyzed all pCLE videos off-line. RESULTS Nineteen biopsies obtained in 13 patients (17 targeted biopsies, 2 random biopsies) revealed the presence of low-grade dysplasia. Thirteen lesions with dysplasia were endoscopically visible but by using pCLE-targeted biopsies, additional endoscopically invisible dysplasias in 4 biopsies obtained from 3 patients were detected. The sensitivity, specificity, and accuracy of pCLE in predicting dysplasia were respectively 89 % (95 % CI: 65 - 98), 96 % (95 % CI: 94 - 97), and 96 % (95 % CI: 94 - 97). pCLE showed a good performance for differentiating neoplastic from non-neoplastic mucosa with negative predictive value of 99 %. CONCLUSIONS pCLE in PSC-IBD surveillance is feasible and may be a good complement to HDE. Future research should aim at elucidating whether real-time pCLE is applicable in PSC-IBD surveillance.
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Affiliation(s)
- Aldona Dlugosz
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden,Corresponding author Aldona Dlugosz, MD, PhD Karolinska Institutet, Department of MedicineKarolinska University Hospital, HuddingeCenter for Digestive DiseasesSE-14186 StockholmSweden+46 8 585 823 43+46 8 585 823 35
| | - Ammar Mohkles Barakat
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Niklas K. Björkström
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden,Department of Medicine Huddinge and Center for Infectious Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Åke Öst
- Department of Pathology Huddinge, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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17
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Sinagra E, Tomasello G, Raimondo D, Sturm A, Giunta M, Messina M, Damiano G, Palumbo VD, Spinelli G, Rossi F, Facella T, Marasà S, Cottone M, Lo Monte AI. Advanced endoscopic imaging for surveillance for dysplasia and colorectal cancer in inflammatory bowel disease: could the pathologist be further helped? Saudi J Gastroenterol 2014; 20:26-38. [PMID: 24496155 PMCID: PMC3952417 DOI: 10.4103/1319-3767.126314] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 11/03/2013] [Indexed: 12/18/2022] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal cancer. The magnitude of that increased risk as well as how best to mitigate it remain a topic of ongoing investigation in the field. It is important to quantify the risk of colorectal cancer in association with IBD. The reported risk varies widely between studies. This is partly due to the different methodologies used in the studies. Because of the limitations of surveillance strategies based on the detection of dysplasia, advanced endoscopic imaging and techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated. Development of new biomarkers, predicting future occurrence of colonic neoplasia may lead to more biomarker-based surveillance. There are promising results that may lead to more efficient surveillance in IBD patients and more general acceptance of its use. A multidisciplinary approach, involving in particular endoscopists and pathologists, together with a centralized patient management, could help to optimize treatments and follow-up measures, both of which could help to reduce the IBD-associated cancer risk.
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Affiliation(s)
- Emanuele Sinagra
- PhD Course in Surgical Biotechnology and Regenerative Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
- Ospedale San Raffaele - Giglio, Gastroenterology and Endoscopy Unit, Cefalù, Italy
| | - Giovanni Tomasello
- DICHIRONS Department, School of Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
| | - Dario Raimondo
- Ospedale San Raffaele - Giglio, Gastroenterology and Endoscopy Unit, Cefalù, Italy
| | - Andreas Sturm
- Krankenhaus Waldfriede, Akademisches Lehrkrankenhaus DER Charite, Argentinische Allee 40, 14163 Berlin, Germany
| | - Marco Giunta
- Ospedali Riuniti Villa Sofia - Cervello, Unit of Gastroenterology, via Trabucco 180, 90146 Palermo, Italy
| | - Marco Messina
- Ospedale San Raffaele - Giglio, Unit of Oncology, Cefalù, Italy
| | - Giuseppe Damiano
- AOUP Paolo Giaccone, School of Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
| | - Vincenzo D. Palumbo
- AOUP Paolo Giaccone, School of Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
| | - Gabriele Spinelli
- AOUP Paolo Giaccone, School of Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
| | - Francesca Rossi
- Ospedale San Raffaele - Giglio, Gastroenterology and Endoscopy Unit, Cefalù, Italy
| | - Tiziana Facella
- Ospedale San Raffaele - Giglio, Gastroenterology and Endoscopy Unit, Cefalù, Italy
| | | | - Mario Cottone
- DIBIMIS Department, Ospedali Riuniti Villa Sofia - Cervello, Unit of Internal Medicine, via Trabucco 180, 90146 Palermo, Italy
| | - Attilio I. Lo Monte
- DICHIRONS Department, School of Medicine, University of Palermo, via Trabucco 180, 90146 Palermo, Italy
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18
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Liu J, Dlugosz A, Neumann H. Beyond white light endoscopy: The role of optical biopsy in inflammatory bowel disease. World J Gastroenterol 2013; 19:7544-7551. [PMID: 24282344 PMCID: PMC3837252 DOI: 10.3748/wjg.v19.i43.7544] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 10/08/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
In this review, we will discuss the use of two optical biopsy modalities in inflammatory bowel disease (IBD). The two techniques reviewed here are confocal laser endomicroscopy and endocytoscopy. We will describe the technical performance of the procedure, discuss the clinical indications for optical biopsy in IBD, and highlight active research areas with respect to the pathogenesis of IBD. Clinical indications for optical biopsies in IBD include assessment of mucosal inflammation, dysplasia detection and evaluation of cell shedding for disease relapse. Research application in the area of barrier dysfunction will also be discussed.
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19
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Fassan M, Baffa R, Kiss A. Advanced precancerous lesions within the GI tract: the molecular background. Best Pract Res Clin Gastroenterol 2013; 27:159-169. [PMID: 23809238 DOI: 10.1016/j.bpg.2013.03.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 02/14/2013] [Accepted: 03/08/2013] [Indexed: 01/31/2023]
Abstract
The mainstream carcinogenic processes involved within the gastrointestinal tract are characterized by phenotypic multistep progression cascades that eventually result in full-blown cancers. In this scenario, the understanding of the molecular dysregulations underlying the precancerous lesions is increasing but still remains incomplete. However, in recent years, the enthusiastic rise of innovative technologies (i.e., next-generation sequencing, high-throughput microarray analysis, mass spectrometry based proteomics) and the unexpected discovery of new classes of biomarkers (i.e., miRNA, long-noncoding RNAs) prompted new strength in the exploration of the accurate and comprehensive molecular characterization of premalignant and malignant neoplastic lesions. The challenge ahead lies in the reliable identification of disease progression-specific targets to enable molecular testing in the clinical management of the secondary prevention of gastrointestinal cancers.
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Affiliation(s)
- Matteo Fassan
- Department of Medicine DIMED, Surgical Pathology & Cytopathology Unit, University of Padua, 35121 Padua, Italy.
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