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López-Serrano A, Pretel L. Virtual chromoendoscopy for the identification of colonic dysplasia in patients with inflammatory bowel disease. A systematic review. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025; 117. [PMID: 39968657 DOI: 10.17235/reed.2025.9878/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Patients with inflammatory bowel disease (IBD) in the colon have a higher risk for colorectal cancer (CRC). Virtual chromoendoscopy (VCE) allows identification and assessment of colonic dysplasia, which might displace dye-based chromoendoscopy (DCE) as the endoscopist's technique of choice for these patients within endoscopic surveillance programs. OBJECTIVE to analyze the best evidence available on the usefulness of VCE versus DCE for dysplasia identification in patients with long-standing colonic IBD. MATERIAL AND METHODS a qualitative, PRISMA 2020-based systematic review of the literature was carried out in the PubMed, Science Direct, and Scielo databases until June 2023. Clinical trials, case-control studies, comparative studies, and crossover studies in English or Spanish were included that directly compared DCE versus VCE for the screening of colonic dysplasia in patients with IBD. The Quality Assessment of Diagnostic Accuracy studies (QUADAS) 2 was used for assessing study quality. The selected studies were evaluated by 2 independent researchers, who entered their abstracted results into a database. RESULTS out of 141 identified studies 9 were selected that compared DCE with VCE (1131 patients included). Six studies are prospective, randomized, controlled trials; 2 are retrospective case-control studies; and 1 is a prospective comparative study. VCE showed a dysplasia detection ability similar to that of DCE, albeit with shorter examination times (8 studies; 985 patients). Factors associated with dysplasia identification included lesions in the right colon (3 studies; 581 patients); non-polypoid lesions (1 study; 210 patients) and/or lesions with Kudo's type III-V pit patterns (2 studies; 254 patients); and patient age (1 study; 129 patients). CONCLUSIONS VCE may be an alternative to DCE for CRC screening in patients with long-standing IBD, with similar detection ability for colonic dysplasia and the benefit of shorter procedure times. Currently available evidence is limited in this regard given the small numbers of patients in the relevant studies, hence further research is necessary with greater numbers of included subjects.
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Affiliation(s)
| | - Luis Pretel
- Facultat de Medicina, Universitat de Valencia
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2
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Urquhart SA, Pallipamu N, Voruganti HV, Baraskar B, Muddaloor P, Sethi AK, Redij R, Aedma K, Gopalakrishnan K, Poigai Arunachalam S, Burger KN, Mahoney DW, Kassmeyer BA, Lennon RJ, Kisiel JB, Coelho-Prabhu N. Nonconventional dysplasia in patients with inflammatory bowel disease and colorectal adenocarcinoma: a case-cohort study. J Crohns Colitis 2025; 19:jjaf022. [PMID: 39901738 DOI: 10.1093/ecco-jcc/jjaf022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel disease (IBD) face increased risk of colorectal cancer (CRC). While the natural history of conventional dysplastic precursor lesions has been well-studied, the neoplastic potential of recently described nonconventional (NC) IBD-associated colonic mucosal lesions is unclear. We aimed to assess the incidence of antecedent NC lesions in patients with IBD who developed CRC. METHODS A case-cohort study was performed to include patients with a diagnosis of IBD with or without CRC who underwent at least 2 surveillance endoscopic procedures at our institution between 1/1/2007 and 5/31/2023. NC lesions included serrated change and indefinite for dysplasia. Detection rates pre- and post-introduction of high-definition (HD) surveillance colonoscopy were compared. RESULTS In total, 87 patients with IBD and CRC and 200 patients with IBD without CRC were identified. Of the cases, a majority had ulcerative colitis (n = 52, 60%), most commonly with extensive involvement (n = 46, 89%). Conventional (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.34-3.52) and NC (HR 2.28, 95% CI 1.59-3.26) lesions were associated with increased risk of CRC. Conventional lesions in the post-HD era appeared to have a stronger association with CRC (HR 2.79, 95% CI 1.62-4.77) than NC lesions (HR 1.62, 95% CI 0.86-3.06). CONCLUSIONS Both conventional and NC lesions seem to be associated with increased risk of CRC. Conventional lesions are more strongly associated with CRC than NC lesions in the post-HD era, but misclassifications in the pre-HD era may have resulted in a biased increased risk estimate for NC lesions.
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Affiliation(s)
- Siri A Urquhart
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Namratha Pallipamu
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Hima Varsha Voruganti
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Bhavana Baraskar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Pratyusha Muddaloor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Arshia K Sethi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Renisha Redij
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Keirthana Aedma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | | | | | - Kelli N Burger
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States
| | - Douglas W Mahoney
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States
| | - Blake A Kassmeyer
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States
| | - Ryan J Lennon
- Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, United States
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
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Lucaciu LA, Despott EJ. Advanced Endoscopic Imaging for Detection of Dysplasia in Inflammatory Bowel Disease. Gastrointest Endosc Clin N Am 2025; 35:141-158. [PMID: 39510684 DOI: 10.1016/j.giec.2024.04.011] [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: 11/15/2024]
Abstract
Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer. Dysplasia is often found in flat, subtle mucosal abnormalities; therefore, early detection is essential. Innovative enhanced endoscopy imaging techniques are increasingly available for endoscopists managing IBD, allowing an in-depth, close to histology evaluation of mucosal pattern and vascular architecture. These new tools enable an earlier and more accurate detection and assessment of dysplasia, leading to improved patientoutcomes. This review provides an exhaustive overview of these techniques and their applicability in the clinical practice.
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Affiliation(s)
- Laura Alexandra Lucaciu
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, Pond Street, London NW3 2QG, UK; Iuliu Hatieganu University of Medicine and Pharmacy, Victor Babes 8, 400347, Cluj-Napoca, Romania
| | - Edward John Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, Pond Street, London NW3 2QG, UK; University College London (UCL) School of Medicine, Gower Street, London WC1E 6BT, UK.
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4
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Xia K, Gao R, Li L, Wu X, Wu T, Ruan Y, Yin L, Chen C. Transformation of colitis and colorectal cancer: a tale of gut microbiota. Crit Rev Microbiol 2024; 50:653-662. [PMID: 37671830 DOI: 10.1080/1040841x.2023.2254388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/24/2023] [Accepted: 08/28/2023] [Indexed: 09/07/2023]
Abstract
Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.
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Affiliation(s)
- Kai Xia
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Renyuan Gao
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lin Li
- Department of Thyroid and Breast Surgery, Ningbo Medical Center, Li Huili Hospital, Ningbo, China
| | - Xiaocai Wu
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tianqi Wu
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yu Ruan
- Surgery and Anesthesia Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lu Yin
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chunqiu Chen
- Diagnostic and Treatment Center for Refractory Diseases of Abdomen Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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Fanizza J, Bencardino S, Allocca M, Furfaro F, Zilli A, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S, D'Amico F. Inflammatory Bowel Disease and Colorectal Cancer. Cancers (Basel) 2024; 16:2943. [PMID: 39272800 PMCID: PMC11394070 DOI: 10.3390/cancers16172943] [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: 07/29/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.
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Affiliation(s)
- Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privè Ambroise Parè-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
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Picardo S, Venugopal K, Cheng W, Ragunath K. Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study. J Gastroenterol Hepatol 2024; 39:506-511. [PMID: 38069495 DOI: 10.1111/jgh.16438] [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: 06/05/2023] [Revised: 11/05/2023] [Accepted: 11/14/2023] [Indexed: 03/05/2024]
Abstract
BACKGROUND AND AIM Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer as compared with the general population. Endoscopic surveillance to detect early dysplastic changes is advised by several published clinical guidelines, which provide recommendations as to the timing and performance of surveillance procedures. There is a paucity of data as to adherence with these guidelines in clinical practice. METHODS A longitudinal inception cohort study of all new patients diagnosed with inflammatory bowel disease across a service network of Australian hospitals between January 2005 and June 2014, with continuous follow-up in a gastroenterology clinic until December 31, 2022. Patients were included if they warranted surveillance according to the Australian guidelines. Adherence to guidelines and technical and quality measures were reported. RESULTS A total of 136 patients were included, and a total of 263 surveillance procedures were performed. Ninety-five patients (70%) had their first surveillance colonoscopy within the correct time interval. Fifty patients (37%) were completely adherent to guidelines with respect to timing of all surveillance procedure. The overall dysplasia detection rate for surveillance procedures was 10%. Chromoendoscopy was only performed in 16% of procedures. CONCLUSIONS Adherence to endoscopic surveillance guidelines with regard to timing of procedures and the utilization of chromoendoscopy is poor. Further clinician education, promotion of the surveillance guidelines and incorporation of chromoendoscopy training as part of the national colonoscopy training program may improve adherence to guidelines.
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Affiliation(s)
- Sherman Picardo
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
| | - Kannan Venugopal
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Wendy Cheng
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
| | - Krish Ragunath
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia, Australia
- Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Western Australia, Australia
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Te Groen M, Derks M, den Broeder N, Peters C, Dijkstra G, de Vries A, Romkens T, Horjus C, de Boer N, de Jong M, Nagtegaal I, Derikx L, Hoentjen F. Quality of Surveillance Impacts the Colitis-Associated Advanced Neoplasia Risk: A Multicenter Case-Control Study. Clin Gastroenterol Hepatol 2024; 22:357-367.e5. [PMID: 36572110 DOI: 10.1016/j.cgh.2022.12.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 11/09/2022] [Accepted: 12/08/2022] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIMS Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD. METHODS In this multicenter case-control study, we searched the Dutch nationwide pathology databank to identify IBD cases with AN and controls with indefinite or low-grade dysplasia. The surveillance colonoscopy preceding the index lesion (first indefinite for dysplasia [IND]/low-grade dysplasia [LGD] or AN) was used to assess the impact of surveillance quality. We assessed intervals, bowel preparation, cecal intubation, and absence of inflammation as primary quality indicators. In addition, we assessed chromoendoscopy, endoscopist expertise, hospital setting, and biopsy strategy. Associations of quality indicators with AN risk were determined with multivariable logistic regression analyses with Firth's correction. RESULTS We included 137 cases and 138 controls. Delayed intervals (58.2% vs 39.6%) and active inflammation (65.3% vs 41.8%) were frequently present in cases and controls and were associated with AN (delayed interval: adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.07-3.81; P = .03; active inflammation: aOR, 2.46; 95% CI, 1.33-4.61; P < .01). Surveillance compliant with primary quality indicators was associated with a reduced AN risk (aOR, 0.43; 95% CI, 0.22-0.91; P = .03), similar to chromoendoscopy (OR, 0.11; 95% CI, 0.01-0.89; P = .01). Other indicators were not significantly associated with AN. CONCLUSIONS Surveillance compliant with primary quality indicators is associated with a reduced colitis-associated AN risk. Delayed surveillance intervals and active inflammation were associated with an increased AN risk. This underlines the importance of procedural quality, including endoscopic remission to optimize the effectiveness of endoscopic surveillance.
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Affiliation(s)
- Maarten Te Groen
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands.
| | - Monica Derks
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Nathan den Broeder
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Charlotte Peters
- Department of Gastroenterology, Amsterdam University Medical Center, location AMC, Amsterdam, the Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology, Groningen University Medical Center, Groningen, the Netherlands
| | - Annemarie de Vries
- Department of Gastroenterology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Tessa Romkens
- Department of Gastroenterology, Jeroen Bosch Hospital, Den Bosch, the Netherlands
| | - Carmen Horjus
- Department of Gastroenterology, Rijnstate Hospital, Arnhem, the Netherlands
| | - Nanne de Boer
- Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Michiel de Jong
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lauranne Derikx
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Gastroenterology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Frank Hoentjen
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands; Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada
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Itzkowitz S, Farraye FA, Limburg PJ, Gagrat Z, Olson MC, Zella J, Kisiel JB. Assessment of Stool DNA Markers to Detect Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: A Multi-site Case-control Study. J Crohns Colitis 2023; 17:1436-1444. [PMID: 37166153 PMCID: PMC10588779 DOI: 10.1093/ecco-jcc/jjad069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Indexed: 05/12/2023]
Abstract
BACKGROUND AND AIMS The FDA-approved multitarget stool-DNA [mt-sDNA] test is a successful colorectal cancer [CRC] screening tool in average-risk individuals but is not indicated for patients with inflammatory bowel disease [IBD]. We determined the performance of the mt-sDNA assay without the haemoglobin component [mt-sDNAHgb-] in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia [ACRN]. METHODS This was a multi-centre, proof-of-concept investigation in persons aged 18-84 years with a diagnosis of IBD, or primary sclerosing cholangitis [PSC] with IBD. Enrolment occurred between March 2013 and May 2016. Stool was tested with the mt-sDNA molecular markers only, minus the immunochemical haemoglobin component. RESULTS The analysis set contained 355 samples. The median age was 52 [range 39-62] years, 45.6% were female and 93% were White. Two-thirds [63%] had ulcerative colitis [UC] and 10.1% had PSC/IBD. Colonoscopy revealed cancer in 8.5% [N = 30], advanced precancerous lesions [APLs] in 9.3% [N = 33] and non-advanced precancerous lesions in 7.6% [N = 27], and three-quarters [74.7%, N = 265] had negative findings. mt-sDNAHgb- sensitivity was 73.3% for any stage cancers, and 76.2% for ACRN. Sensitivity was highest for IBD-associated high-grade dysplasia at 100% and 84.6% for IBD-associated low-grade dysplasia ≥1 cm. The test showed higher sensitivity and lower specificity in UC than in Crohn's disease. Increasing inflammation score was associated with a significant decrease in mt-sDNAHgb- test score [ = 0.028] amongst neoplasia-negative individuals, but not in patients with ACRN. CONCLUSIONS These data highlight the potential of multitarget stool-DNA marker testing as an important addition to colorectal cancer surveillance by complementing colonoscopic evaluations in IBD patients.
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Affiliation(s)
| | | | | | | | | | - Julia Zella
- Exact Sciences Corporation, Madison, WI, USA
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Chiu LS, Calderwood AH. Noninvasive Colorectal Cancer Prevention Options in Older Adults. J Clin Gastroenterol 2023; 57:855-862. [PMID: 37436836 DOI: 10.1097/mcg.0000000000001893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide and its incidence increases with age. The proportion of older adults in the United States continues to rise, making CRC prevention a key health priority for our aging population. CRC is a largely preventable disease through screening and polyp surveillance, and noninvasive modalities represent an important option for older adults in whom the burdens and risks of invasive testing are higher compared with younger adults. This review highlights the evidence, risks, and benefits of noninvasive CRC screening and surveillance options in older adults and discusses the challenges of CRC prevention in this cohort.
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Affiliation(s)
- Laura S Chiu
- Department of Medicine, Section of Gastroenterology, Boston University School of Medicine, Boston, MA
| | - Audrey H Calderwood
- Department of Medicine, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
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Long D, Alghoul Z, Sung J, Yang C, Merlin D. Prevention of Colitis-Associated Cancer via Oral Administration of M13-Loaded Lipid Nanoparticles. Pharmaceutics 2023; 15:2331. [PMID: 37765299 PMCID: PMC10534593 DOI: 10.3390/pharmaceutics15092331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/09/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease, is known to increase the risk of colitis-associated cancer (CAC). CAC has been found to be unresponsive to standard chemotherapy regimens, and the current treatments do not utilize effective small-molecule drugs and colon-targeted delivery systems. Previous studies indicated that the M13-nano-liposome (NL) formulation can effectively target the colon and reshape the gut microbiota in ex vivo cultures, generating altered microbial metabolites that can efficiently prevent chronic UC. In this study, we tested the cancer cell uptake ability of the NL formulation and investigated the potential of the M13-NL formulation to prevent CAC in the azoxymethane (AOM)-exposed IL10-/- mouse model. Our findings demonstrate that oral administration of M13-NL prevents tumor development in AOM-exposed IL10-/- mice, suggesting that M13-NL is a promising oral drug formulation for preventing CAC.
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Affiliation(s)
- Dingpei Long
- Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; (D.L.); (Z.A.); (J.S.); (D.M.)
| | - Zahra Alghoul
- Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; (D.L.); (Z.A.); (J.S.); (D.M.)
- Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
| | - Junsik Sung
- Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; (D.L.); (Z.A.); (J.S.); (D.M.)
| | - Chunhua Yang
- Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; (D.L.); (Z.A.); (J.S.); (D.M.)
- Gastroenterology Research, Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA
| | - Didier Merlin
- Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; (D.L.); (Z.A.); (J.S.); (D.M.)
- Gastroenterology Research, Atlanta Veterans Affairs Medical Center, Decatur, GA 30302, USA
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Sato Y, Tsujinaka S, Miura T, Kitamura Y, Suzuki H, Shibata C. Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers (Basel) 2023; 15:4154. [PMID: 37627182 PMCID: PMC10452690 DOI: 10.3390/cancers15164154] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/13/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.
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Affiliation(s)
| | - Shingo Tsujinaka
- Division of Gastroenterological Surgery, Department of Surgery, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan
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12
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Kim JE, Choi CW, Hong SN, Song JH, Kim ER, Chang DK, Kim YH. Incremental Detection Rate of Dysplasia and Sessile Serrated Polyps/Adenomas Using Narrow-Band Imaging and Dye Spray Chromoendoscopy in Addition to High-Definition Endoscopy in Patients with Long-Standing Extensive Ulcerative Colitis: Segmental Tandem Endoscopic Study. Diagnostics (Basel) 2023; 13:diagnostics13030516. [PMID: 36766621 PMCID: PMC9914536 DOI: 10.3390/diagnostics13030516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/19/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
High-definition (HD) endoscopy is recommended in surveillance colonoscopy for detecting dysplasia in patients with ulcerative colitis (UC). Dye-spray chromoendoscopy (DCE) and narrow-band imaging (NBI) are often used as adjunctive techniques of white-light endoscopy (WLE) in real-world practice. However, the incremental detection ability of DCE and NBI added to HD-WLE for dysplasia and serrated lesions has not yet been evaluated using tandem endoscopy in patients with long-standing extensive UC. We enrolled patients with extensive UC for >8 years who were in clinical remission (partial Mayo score < 2) at the Samsung Medical Center in Seoul, Republic of Korea. HD-WLE was performed first. Subsequently, HD-NBI and HD-DCE with indigo carmine were performed using the segmental tandem colonoscopy technique. A total of 40 patients were eligible, and data obtained from 33 patients were analyzed. The incremental detection rates (IDRs) for dysplasia and serrated lesions were calculated. HD-WLE detected three dysplasia and five sessile serrated adenomas/polyps (SSAs/Ps). HD-NBI and HD-DCE did not detect additional dysplasia (IDR = 0%; 95% confidence interval (CI): 0-56.2%). HD-NBI identified one missed SSA/P (IDR = 7.7%; 95% CI: 1.4-33.3%), and HD-DCE detected seven missed SSAs/Ps (IDR = 53.9%; 95% CI: 29.1-76.8%). Logistic regression found that HD-DCE increased the detection of SSAs/Ps compared to HD-WLE and/or HD-NBI (odds ratio (OR) = 3.16, 95% CI: 0.83-11.92, p = 0.08). DCE in addition to HD-WLE improved the detection of SSAs/Ps, but not dysplasia, in patients with long-standing extensive UC.
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13
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Clinical features and oncological outcomes of intestinal cancers associated with ulcerative colitis and Crohn's disease. J Gastroenterol 2023; 58:14-24. [PMID: 36182971 DOI: 10.1007/s00535-022-01927-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 09/21/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease. METHODS Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.. RESULTS A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients. CONCLUSIONS The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.
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14
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Kim HS, Hernaez R, Sansgiry S, Waljee AK, Scott FI, Lewis JD, El-Serag HB, Hou JK. Comparative Effectiveness of Surveillance Colonoscopy Intervals on Colorectal Cancer Outcomes in a National Cohort of Patients with Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2022; 20:2848-2857.e2. [PMID: 35240331 PMCID: PMC9489337 DOI: 10.1016/j.cgh.2022.02.048] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 01/20/2022] [Accepted: 02/17/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown. METHODS We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 year, 1 to 3 years, 3 to 5 years, or none within 5 years. RESULTS Among 566 patients with CRC-IBD, most (69.4%) did not have colonoscopy within 5 years prior to CRC diagnosis, whereas 9.7% had colonoscopy within 1 year prior to diagnosis, 17.7% within 1 to 3 years, and 3.1% between 3 and 5 years. Compared with no surveillance, colonoscopy within 1 year (adjusted odds ratio, 0.40; 95% confidence interval [CI], 0.20-0.82), and 1 to 3 years (adjusted odds ratio, 0.56; 95% CI, 0.32-0.98) were less likely to be diagnosed at late stage. Regardless of IBD type and duration, colonoscopy within 1 year was associated with a lower all-cause mortality (adjusted hazard ratio, 0.56; 95% CI, 0.36-0.88). CONCLUSIONS In a national cohort of patients with CRC-IBD, colonoscopy within 3 years prior to CRC diagnosis was associated with early tumor stage at diagnosis, and colonoscopy within 1 year was associated with a reduced all-cause mortality compared with no colonoscopy. Our findings support colonoscopy intervals of 1 to 3 years in patients with IBD to reduce late-stage CRC and all-cause mortality.
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Affiliation(s)
- Hyun-Seok Kim
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Ruben Hernaez
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Shubhada Sansgiry
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Health Services Research, Baylor College of Medicine, Houston, Texas
| | - Akbar K Waljee
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; Health Services Research and Development Center of Clinical Management Research, Veterans Administration Ann Arbor, Ann Arbor, Michigan
| | - Frank I Scott
- Division of Gastroenterology, University of Colorado, Aurora, Colorado
| | - James D Lewis
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Jason K Hou
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
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15
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Inflammatory Bowel Disease-Associated Colorectal Cancer Epidemiology and Outcomes: An English Population-Based Study. Am J Gastroenterol 2022; 117:1858-1870. [PMID: 36327438 DOI: 10.14309/ajg.0000000000001941] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/29/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. METHODS Using population data from the English National Health Service held in the CRC data repository, all CRCs with and without prior diagnosis of IBD (Crohn's, ulcerative colitis, IBD unclassified, and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the 2 groups and their outcomes up to 2 years. RESULTS Three hundred ninety thousand six hundred fourteen patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis [interquartile range] 66 [54-76] vs 72 [63-79] years [ P < 0.01]), more likely to be diagnosed with CRC as an emergency (25.1% vs 16.7% [ P < 0.01]), and more likely to have a right-sided colonic tumor (37.4% vs 31.5% [ P < 0.01]). Total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn's, 44.1% of ulcerative colitis, 44.5% of IBD unclassified, and 67.7% of IBD with cholangitis). Synchronous (3.2% vs 1.6% P < 0.01) and metachronous tumors (1.7% vs 0.9% P < 0.01) occurred twice as frequently in patients with IBD compared with those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. DISCUSSION IBD-associated CRCs occur in younger patients and have worse outcomes than sporadic CRCs. There is an urgent need to find reasons for these differences to inform screening, surveillance, and treatment strategies for CRC and its precursors in this high-risk group.
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16
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Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention. Curr Oncol 2022; 29:6091-6114. [PMID: 36135048 PMCID: PMC9498229 DOI: 10.3390/curroncol29090479] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/14/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.
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17
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Leite-Gomes E, Dias AM, Azevedo CM, Santos-Pereira B, Magalhães M, Garrido M, Amorim R, Lago P, Marcos-Pinto R, Pinho SS. Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player. Inflamm Bowel Dis 2022; 28:947-962. [PMID: 34849933 DOI: 10.1093/ibd/izab291] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Indexed: 02/06/2023]
Abstract
Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.
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Affiliation(s)
- Eduarda Leite-Gomes
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Ana M Dias
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Catarina M Azevedo
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Beatriz Santos-Pereira
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
| | - Mariana Magalhães
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.,Department of Gastroenterology, Centro Hospitalar e Universitário do Porto, Porto, Portugal
| | - Mónica Garrido
- Department of Gastroenterology, Centro Hospitalar e Universitário do Porto, Porto, Portugal
| | - Rita Amorim
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.,Pediatrics Department, Centro Hospitalar e Universitário São João, Porto, Portugal.,Medical Faculty, University of Porto, Porto, Portugal
| | - Paula Lago
- Department of Gastroenterology, Centro Hospitalar e Universitário do Porto, Porto, Portugal
| | - Ricardo Marcos-Pinto
- Department of Gastroenterology, Centro Hospitalar e Universitário do Porto, Porto, Portugal.,School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,Centre for Research in Health Technologies and Information Systems, University of Porto, Portugal
| | - Salomé S Pinho
- i3S-Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.,School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.,Medical Faculty, University of Porto, Porto, Portugal
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18
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Ballester MP, Mesonero F, Flórez-Diez P, Gómez C, Fuentes-Valenzuela E, Martín N, Senosiain C, Vela M, Fernández-Clotet A, Pérez P, Rubín de Célix C, Calviño-Suárez C, Hermida B, Muñoz R, González-Vivo M, Brunet E, Jiménez N, Botella B, Yebra J, Suárez-Ferrer C, Bouhmidi A, López-Serrano A, Ponferrada Á, Dueñas C, Mínguez M. Adherence to endoscopic surveillance for advanced lesions and colorectal cancer in inflammatory bowel disease: an AEG and GETECCU collaborative cohort study. Aliment Pharmacol Ther 2022; 55:1402-1413. [PMID: 35224758 DOI: 10.1111/apt.16832] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/09/2021] [Accepted: 02/04/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non-adherence. METHODS A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox-proportional regression analyses were used to compare the risk of lesions. p-values below 0.05 were considered significant. RESULTS A total of 1031 patients (732 ulcerative colitis, 259 Crohn's disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24-29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3-10.1; p = 0.016). Risk of delay or non-performance of endoscopic follow-up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462-5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409-7.644; p < 0.001 for intermediate- and high- vs low-risk groups). CONCLUSIONS Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Francisco Mesonero
- Digestive Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Pablo Flórez-Diez
- Digestive Disease Department, Hospital Universitario Central de Asturias, Asturias, Spain
| | - Concepción Gómez
- Digestive Disease Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | | | - Noelia Martín
- Digestive Disease Department, Hospital de Galdakao, Bizkaia, Spain
| | - Carla Senosiain
- Digestive Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Milagros Vela
- Digestive Disease Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Agnes Fernández-Clotet
- Gastroenterology Department, IBD Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Pablo Pérez
- Digestive Disease Department, Hospital Provincial de Pontevedra, Pontevedra, Spain
| | | | | | - Benito Hermida
- Digestive Disease Department, Hospital Universitario de Cabueñes, Asturias, Spain
| | - Roser Muñoz
- Digestive Disease Department, Hospital General de Alicante, Alicante, Spain
| | | | - Eduard Brunet
- Digestive Disease Department, Hospital Parc Taulí, Sabadell, Spain
| | - Nuria Jiménez
- Digestive Disease Department, Hospital General Universitario de Elche, Elche, Spain
| | - Belén Botella
- Digestive Disease Department, Hospital Universitario Infanta Cristina, Madrid, Spain
| | - Jorge Yebra
- Digestive Disease Department, Hospital Universitario de Móstoles, Madrid, Spain
| | | | - Abdel Bouhmidi
- Digestive Disease Department, Hospital Santa Bárbara Puertollano, Puertollano, Spain
| | | | - Ángel Ponferrada
- Digestive Disease Department, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Carmen Dueñas
- Digestive Disease Department, Hospital Universitario de Cáceres, Cáceres, Spain
| | - Miguel Mínguez
- Digestive Disease Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
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19
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Chen HM, MacDonald JA. Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression. Inflamm Bowel Dis 2022; 28:1485-1496. [PMID: 35604388 PMCID: PMC9527615 DOI: 10.1093/ibd/izac098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development. METHODS Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R. RESULTS A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive. CONCLUSION In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia.
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Affiliation(s)
- Huey-Miin Chen
- Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Justin A MacDonald
- Address correspondence to: Justin A. MacDonald, PhD, Department of Biochemistry & Molecular Biology, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6 ()
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20
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Weissman S, Systrom HK, Aziz M, El-Dallal M, Lee-Smith W, Sciarra M, Feuerstein JD. Colorectal Cancer Prevention in Inflammatory Bowel Disease: A Systematic Analysis of the Overall Quality of Guideline Recommendations. Inflamm Bowel Dis 2022; 28:745-754. [PMID: 34245270 DOI: 10.1093/ibd/izab164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Owing to the increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD), numerous societies developed preventative guidelines. We aimed to assess the overall quality of CRC prevention guidelines in IBD. METHODS A systematic search was performed in multiple databases to identify all guidelines pertaining to CRC prevention in IBD in September 2020. All guidelines were reviewed for conflicts of interest (COIs)/funding, recommendation quality/strength, external guideline review, use of patient representation, and plans for update-as per Institute of Medicine standards. In addition, recommendations were compared amongst societies. RESULTS One hundred forty-nine recommendations from 14 different guidelines/societies were included. Not all guidelines provided recommendations on key elements surrounding (1) screening initiation and surveillance, (2) screening modality, (3) pharmacological chemoprevention, (4) dysplasia management and follow-up, and (5) molecular marker use. Only 71% of guidelines disclosed COIs, 43% reported industry funding, 14% were externally reviewed, 7% included patient representation, and 36% had plans for update. Of the total recommendations, 7.4%, 23.5%, and 69.1% were based on high,- moderate-, and low-quality evidence, respectively. Additionally, 20.1% of recommendations were strong, 14.1%, were weak/conditional, and 65.8% did not provide a strength. The proportion of high-quality evidence (P = 0.34) and strong recommendations (P = 0.57) did not significantly differ across societies. CONCLUSIONS Many guidelines do not provide recommendations on key aspects of CRC prevention in IBD. Over 90% of recommendations are based on low- to moderate-quality evidence; therefore, further studies on CRC prevention in IBD are needed to improve the overall quality of evidence.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, New Jersey, USA
| | - Hannah K Systrom
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo Medical Center, Toledo, OH, USA
| | - Mohammed El-Dallal
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Division of Hospital Medicine, Cambridge Health Alliance, Cambridge and Harvard Medical School, MA, USA
| | - Wade Lee-Smith
- Department of Library Sciences, University of Toledo Medical Center, Toledo, OH, USA
| | - Michael Sciarra
- Division of Gastroenterology and Hepatology, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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21
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Matsuura M, Matsumoto T, Naito Y, Saitoh Y, Kanai T, Suzuki Y, Tanaka S, Ogata H, Hisamatsu T. Advanced endoscopy for the management of inflammatory digestive diseases: Review of the Japan Gastroenterological Endoscopy Society core session. Dig Endosc 2022; 34:729-735. [PMID: 35037317 DOI: 10.1111/den.14234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/28/2021] [Accepted: 01/11/2022] [Indexed: 02/08/2023]
Abstract
A series of workshops entitled "Advanced endoscopy in the management of inflammatory digestive disease" was held at the 97th to 100th biannual meeting of the Japan Gastroenterological Endoscopy Society. During these core sessions, research findings concerning various endoscopic practices in the field of inflammatory bowel disease (IBD) were presented, and meaningful discussions were shared on the evolving role and future challenges of endoscopy in IBD. This article reviews these core sessions and discusses current topics on the role of endoscopy, focusing on the diagnosis, disease monitoring, mucosal healing assessments, cancer surveillance, and therapeutic interventions in IBD.
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Affiliation(s)
- Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Medicine, Iwate Medical University, Iwate, Japan
| | - Yuji Naito
- Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yusuke Saitoh
- Digestive Disease Center, Asahikawa City Hospital, Hokkaido, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo, Japan
| | - Yasuo Suzuki
- Department of Gastroenterology, Toho University Sakura Medical Center, Chiba, Japan
| | - Shinji Tanaka
- Endoscopy and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
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22
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Stewart MJ. Does Surveillance Increase Survival? Benefits of Periodic Colonoscopy in Patients with Ulcerative Colitis and Colorectal Cancer. Dig Dis Sci 2022; 67:1704-1706. [PMID: 34318354 DOI: 10.1007/s10620-021-07174-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Michael J Stewart
- Division of Digestive Care and Endoscopy, Department of Medicine, Dalhousie University, QEII - Victoria Building, 9th floor Victoria Building, 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada.
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23
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Periodic Colonoscopies Are Associated with Improved Survival and Prognosis of Colorectal Cancer in Ulcerative Colitis. Dig Dis Sci 2022; 67:1850-1857. [PMID: 34318355 DOI: 10.1007/s10620-021-07151-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 04/15/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND STUDY AIMS This study aimed to identify whether ulcerative colitis (UC) patients who develop colorectal cancer (CRC) present at earlier stages of CRC and have improved survival if prior to their CRC diagnosis, they underwent intermittent follow-up colonoscopies compared to those who have no follow-up colonoscopies. METHODS Patients with UC who developed primary CRC were identified using data provided by the Institute for Clinical Evaluative Sciences. We defined low-risk CRC stage as estimated 5-year survival ≥ 80% compared to high-risk CRC as 5-year survival < 80%. RESULTS A total of 421 patients were identified with UC and CRC. The 15-year mortality rate was significantly higher in those who did not have follow-up colonoscopy (33/74; 44.6%) compared to the follow-up group (105/347; 30.3%) (p = 0.0172). Among the 219 patients with UC with staging information available, patients who did not have follow-up colonoscopy were more likely to present with high-risk CRC (24/31; 77.4%) compared with patients who had follow-up colonoscopies (88/188; 44.4%) (p = 0.0016). Those who underwent follow-up colonoscopies at average intervals ≤ 3 years presented with high-risk CRC 41.3% of the time, which was less than the 48.6% in those with less frequent colonoscopies and 77.4% in those with no follow-up (p = 0.0048). CONCLUSIONS Patients with UC who underwent intermittent follow-up colonoscopies had CRC detected at earlier stages and improvement in all-cause mortality, compared to those who with no follow-up colonoscopies. This may support regular surveillance colonoscopies for patients with UC.
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Shah SC, Itzkowitz SH. Colorectal Cancer in Inflammatory Bowel Disease: Mechanisms and Management. Gastroenterology 2022; 162:715-730.e3. [PMID: 34757143 PMCID: PMC9003896 DOI: 10.1053/j.gastro.2021.10.035] [Citation(s) in RCA: 345] [Impact Index Per Article: 115.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 10/14/2021] [Accepted: 10/25/2021] [Indexed: 12/12/2022]
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC), despite decreases in CRC incidence in recent years. Chronic inflammation is the driver of neoplastic progression, resulting in dysplastic precursor lesions that may arise in multiple areas of the colon through a process of field cancerization. Colitis-associated CRC shares many molecular similarities with sporadic CRC, and preclinical investigations have demonstrated a potential role for the microbiome in concert with the host immune system in the development of colitis-associated colorectal cancer (CAC). Some unique molecular differences occur in CAC, but their role in the pathogenesis and behavior of inflammation-associated cancers remains to be elucidated. Nonconventional types of dysplasia have been increasingly recognized, but their natural history is not well defined, and they have not been incorporated into surveillance algorithms. The concept of cumulative inflammatory burden highlights the importance of considering histologic inflammation over time as an important risk factor for CAC. Dysplasia is arguably the most important risk factor for developing CAC, and advances have been made in the endoscopic detection and removal of precancerous lesions, thereby deferring or avoiding surgical resection. Some of the agents used to treat IBD are chemopreventive. It is hoped that by gaining better control of the underlying inflammation with newer medications and better endoscopic detection and management, a more sophisticated appreciation of clinicopathologic risk factors, and growing awareness of the genetic, immunologic, and environmental causes of colitis- associated neoplasia, that colitis-associated colorectal neoplasia will become even more predictable and manageable in the coming years.
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Affiliation(s)
- Shailja C Shah
- Division of Gastroenterology, University of California San Diego, San Diego, California; GI Section, VA San Diego Healthcare Center, San Diego, California
| | - Steven H Itzkowitz
- The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Wang JH, D’Arcy M, Barnes EL, Freedman ND, Engels EA, Song M. Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States. JNCI Cancer Spectr 2022; 6:pkab096. [PMID: 35071980 PMCID: PMC8767622 DOI: 10.1093/jncics/pkab096] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/08/2021] [Accepted: 10/27/2021] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk. METHODS We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year. IBD was identified by ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for potential confounders. For colorectal cancers, we further adjusted for screening rates. We assessed confounding by medication exposure among patients with prescription drug coverage. RESULTS IBD, CD, and UC were present in 0.8%, 0.3%, and 0.5% in both cancer cases and non-cancer controls. Of 51 cancers examined, IBD was statistically significantly associated with cancers of the small intestine (OR = 2.55, 95% CI = 2.15 to 3.01), intrahepatic (OR = 1.92, 95% CI = 1.47 to 2.51) and extrahepatic bile ducts (OR = 1.75, 95% CI = 1.38 to 2.22), rectum (OR = 1.61, 95% CI = 1.36 to 1.90), and colon (OR = 1.21, 95% CI = 1.10 to 1.33). CD was associated with cancers of the small intestine (OR = 4.55, 95% CI = 3.65 to 5.67), and UC was associated with cancers of the intrahepatic bile ducts (OR = 1.87, 95% CI = 1.34 to 2.61), rectum (OR = 1.80, 95% CI = 1.47 to 2.20), and colon (OR = 1.28, 95% CI = 1.14 to 1.43). After adjusting for medication exposure, IBD was not statistically significantly associated with lung cancer, melanoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome. CONCLUSIONS In this large study among older adults (≥66 years of age), IBD was positively associated with gastrointestinal cancers. Associations with extraintestinal cancers may reflect the effect of immunosuppressive medications.
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Affiliation(s)
- Jeanny H Wang
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Monica D’Arcy
- Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute, Rockville, MD, USA
| | - Edward L Barnes
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Minkyo Song
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
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Classification of the Confocal Microscopy Images of Colorectal Tumor and Inflammatory Colitis Mucosa Tissue Using Deep Learning. Diagnostics (Basel) 2022; 12:diagnostics12020288. [PMID: 35204379 PMCID: PMC8870781 DOI: 10.3390/diagnostics12020288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/21/2022] [Accepted: 01/21/2022] [Indexed: 12/09/2022] Open
Abstract
Confocal microscopy image analysis is a useful method for neoplasm diagnosis. Many ambiguous cases are difficult to distinguish with the naked eye, thus leading to high inter-observer variability and significant time investments for learning this method. We aimed to develop a deep learning-based neoplasm classification model that classifies confocal microscopy images of 10× magnified colon tissues into three classes: neoplasm, inflammation, and normal tissue. ResNet50 with data augmentation and transfer learning approaches was used to efficiently train the model with limited training data. A class activation map was generated by using global average pooling to confirm which areas had a major effect on the classification. The proposed method achieved an accuracy of 81%, which was 14.05% more accurate than three machine learning-based methods and 22.6% better than the predictions made by four endoscopists. ResNet50 with data augmentation and transfer learning can be utilized to effectively identify neoplasm, inflammation, and normal tissue in confocal microscopy images. The proposed method outperformed three machine learning-based methods and identified the area that had a major influence on the results. Inter-observer variability and the time required for learning can be reduced if the proposed model is used with confocal microscopy image analysis for diagnosis.
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27
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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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Nakase H, Uchino M, Shinzaki S, Matsuura M, Matsuoka K, Kobayashi T, Saruta M, Hirai F, Hata K, Hiraoka S, Esaki M, Sugimoto K, Fuji T, Watanabe K, Nakamura S, Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol 2021; 56:489-526. [PMID: 33885977 PMCID: PMC8137635 DOI: 10.1007/s00535-021-01784-1] [Citation(s) in RCA: 251] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.
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Affiliation(s)
- Hiroshi Nakase
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan ,grid.263171.00000 0001 0691 0855Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuoku, Sapporo, Hokkaido 060-8543 Japan
| | - Motoi Uchino
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shinichiro Shinzaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Minoru Matsuura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Katsuyoshi Matsuoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Taku Kobayashi
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Masayuki Saruta
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Fumihito Hirai
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Keisuke Hata
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Sakiko Hiraoka
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Motohiro Esaki
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Ken Sugimoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshimitsu Fuji
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kenji Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Shiro Nakamura
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nagamu Inoue
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Toshiyuki Itoh
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Makoto Naganuma
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tadakazu Hisamatsu
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Mamoru Watanabe
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the “Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease”, The Japanese Society of Gastroenterology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004 Japan
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Mackiewicz T, Sowa A, Fichna J. Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends. Curr Drug Targets 2021; 22:137-145. [PMID: 32077822 DOI: 10.2174/1389450121666200220123844] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/20/2019] [Accepted: 01/29/2020] [Indexed: 02/08/2023]
Abstract
Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with a mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples, is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made, thanks to continuous extensive research in this field, however, no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can easily be tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.
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Affiliation(s)
- Tomasz Mackiewicz
- Department Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | | | - Jakub Fichna
- Department Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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30
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Santi G, Michetti P, Froehlich F, Rossel JB, Pittet V, Maillard MH. Adherence to Recommendations and Quality of Endoscopic Colorectal Cancer Surveillance in Long-Standing Ulcerative Colitis. Inflamm Intest Dis 2020; 6:25-31. [PMID: 33850836 DOI: 10.1159/000511010] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/20/2020] [Indexed: 12/21/2022] Open
Abstract
Background Long-standing ulcerative colitis has been associated with an increased risk of colorectal cancer (CRC). Current guidelines recommend endoscopic CRC screening after 8 years of disease duration. The objectives of our study were to assess the adherence to recommendations and the quality of endoscopic procedure in long-standing ulcerative colitis. Methods This is a retrospective cohort study. We selected patients included in the Swiss IBD cohort with a disease duration of ≥8 years and an extension above the rectosigmoid junction. The complementary medical chart review focused on endoscopy and associated histological reports in 8 Swiss centers. Descriptive analyses focused on patients and their colonoscopies. Results 309 colonoscopies were conducted among 116 patients with the following characteristics: women 47%, mean age at diagnosis 31 years, and pancolitis disease extent in 65.5% of cases; 38.8% of patients had a first screening colonoscopy <8 years, 13.8% between 8 and 10 years, and 47.4% >10 years. Cecal intubation was performed in 94.5% of cases, and bowel preparation was good to excellent in 61.5% of endoscopies. Chromoendoscopy was used in 7.4% of cases, and the mean withdrawal time was 16.4 min. Dysplasia was found in 6.2% of cases. Conclusion Despite current international recommendations, a significant number of patients did not receive a proper endoscopic surveillance. An increased use of chromoendoscopy, monitoring of withdrawal time, and appropriate bowel preparation would increase the quality of CRC screening. The adherence to screening guidelines and endoscopic quality should be promoted and standardized.
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Affiliation(s)
- Giulia Santi
- Faculty of Biology & Medicine, University of Lausanne, Lausanne, Switzerland
| | - Pierre Michetti
- Crohn's & Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland.,Service of Gastroenterology & Hepatology, Lausanne University Hospital, Lausanne, Switzerland
| | - Florian Froehlich
- Division of Gastroenterology & Hepatology, Basel University Hospital, Basel, Switzerland
| | - Jean-Benoît Rossel
- Center for Primary Care & Public Health, University of Lausanne, Lausanne, Switzerland
| | - Valérie Pittet
- Center for Primary Care & Public Health, University of Lausanne, Lausanne, Switzerland
| | - Michel H Maillard
- Crohn's & Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland.,Service of Gastroenterology & Hepatology, Lausanne University Hospital, Lausanne, Switzerland
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Ratna Raju B, Swamy G, Padma Raju K. Diagnosis of colorectal cancer based on imperialist competitive algorithm. JOURNAL OF INTELLIGENT & FUZZY SYSTEMS 2020. [DOI: 10.3233/jifs-189021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The Colorectal cancer leads to more number of death in recent years. The diagnosis of Colorectal cancer as early is safe to treat the patient. To identify and treat this type of cancer, Colonoscopy is applied commonly. The feature selection based methods are proposed which helps to choose the subset variables and to attain better prediction. An Imperialist Competitive Algorithm (ICA) is proposed which helps to select features in identification of colon cancer and its treatment. Also K-Nearest Neighbor (KNN) classifier is used to retain a minimal Euclidean distance between the feature of query vector and all the data in the nature of prototype training. Experimental results have proved that the proposed method is superior when compared to other methods in its metrics of performance. Better accuracy is achieved by the proposed method.
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Affiliation(s)
- B Ratna Raju
- Professor of ECE, Miracle Educational Society group of Institutions, Bhogapuram, Vizianagaram Dt. AP
| | - G.N Swamy
- Professor and HOD, -EIE, VR Siddhartha Engineering College (A), Vijayawada, AP
| | - K. Padma Raju
- Professor of ECE, University College of Engineering, JNTUK, Kakinada and Member of APPSC
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Vitello A, Shahini E, Macaluso FS, Morreale GC, Sinagra E, Pallio S, Maida M. Endoscopic surveillance of colorectal cancer in inflammatory bowel diseases: a review of the literature. Expert Rev Anticancer Ther 2020; 20:851-863. [PMID: 32811225 DOI: 10.1080/14737140.2020.1813030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The risk of colorectal cancer (CRC) in patients with inflammatory bowel diseases (IBD) is higher compared to the general population and it is related to the type, severity, duration, and extension of the disease. AREAS COVERED This review aims to highlight current evidence from the literature supporting the role of endoscopic surveillance of CRC in patients with IBD. EXPERT OPINION Even in the absence of randomized controlled trials (RCTs), evidence from the literature supports the effectiveness of endoscopic surveillance in reducing IBD-related CRC incidence and mortality. As a consequence, current guidelines recommend colonoscopy 8-10 years after disease or symptom onset in all patients with ulcerative colitis (UC) and Crohn's disease (CD) involving at least one-third of the colon and agree on the necessity of annual surveillance in high-risk patients. Nevertheless, an overall agreement on the optimal intervals for surveillance of low-intermediate risk patients is absent and 2-5 year intervals have been proposed. In the near future, further studies are needed to assess the most effective intervals and tailor the surveillance based on the personal risk profile. Additionally, further efforts should be made to evaluate the role of noninvasive tests as primary screening, thus avoiding unnecessary colonoscopies.
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Affiliation(s)
- Alessandro Vitello
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Endrit Shahini
- Diagnostic and Interventional Endoscopy, Candiolo Cancer Institute, FPO - IRCCS - Candiolo , Torino, Italy
| | - Fabio S Macaluso
- Internal Medicine, Villa Sofia - V. Cervello Hospital , Palermo, Italy
| | - Gaetano C Morreale
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Istituto San Raffaele Giglio , Cefalù, Italy
| | - Socrate Pallio
- Digestive Diseases Endoscopy Unit, Policlinico G. Martino Hospital, University of Messina , Messina, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
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Zhang J, Chen G, Li Z, Zhang P, Li X, Gan D, Cao X, Du H, Zhang J, Zhang L, Ye Y. Colonoscopic screening is associated with reduced Colorectal Cancer incidence and mortality: a systematic review and meta-analysis. J Cancer 2020; 11:5953-5970. [PMID: 32922537 PMCID: PMC7477408 DOI: 10.7150/jca.46661] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 08/03/2020] [Indexed: 12/15/2022] Open
Abstract
It is the great priority to detect colorectal cancer (CRC) as early as possible, finally to reduce the incidence and mortality of CRC. However, although colonoscopy is recommended in many consensuses, yet no one systematic review is conducted to figure out how colonoscopy could change the incidence and mortality. In our study, we conducted a comprehensive meta-analysis to evaluate the association between colonoscopy screening and the incidence or mortality of CRC. PubMed, EMBASE, and PMC database were systematically searched from their inception to June 2020. A total of 13 cohort and 16 case-control studies comprising 4,713,778 individuals were obtained in this review. Our results showed that colonoscopy was associated with a 52% RR reduction in incidence of CRC (RR: 0.48, 95% CI: 0.46-0.49) and 62% RR reduction in mortality of CRC (RR: 0.38, 95% CI: 0.36-0.40). Subgroup analysis of different interventions, study design, country, sample size, age or sex showed that the incidence and mortality reduction remained consistent, and colonoscopy screening had the same effect on people below and above 50. Our study indicated that colonoscopy could significantly reduce the incidence and mortality of CRC.
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Affiliation(s)
- Jiaxin Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Guang Chen
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Zhiguo Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Peng Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Xiaoke Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Da'nan Gan
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Xu Cao
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Hongbo Du
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Jiaying Zhang
- Ministry of Education Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Ludan Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
| | - Yong'an Ye
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine
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Nebbia M, Yassin NA, Spinelli A. Colorectal Cancer in Inflammatory Bowel Disease. Clin Colon Rectal Surg 2020; 33:305-317. [PMID: 32968366 DOI: 10.1055/s-0040-1713748] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with inflammatory bowel disease (IBD) are at an increased risk for developing colorectal cancer (CRC). However, the incidence has declined over the past 30 years, which is probably attributed to raise awareness, successful CRC surveillance programs and improved control of mucosal inflammation through chemoprevention. The risk factors for IBD-related CRC include more severe disease (as reflected by the extent of disease and the duration of poorly controlled disease), family history of CRC, pseudo polyps, primary sclerosing cholangitis, and male sex. The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CRC. IBD-related CRC is characterized by fewer rectal tumors, more synchronous and poorly differentiated tumors compared with sporadic cancers. There is no significant difference in sex distribution, stage at presentation, or survival. Surveillance is vital for the detection and subsequently management of dysplasia. Most guidelines recommend initiation of surveillance colonoscopy at 8 to 10 years after IBD diagnosis, followed by subsequent surveillance of 1 to 2 yearly intervals. Traditionally, surveillance colonoscopies with random colonic biopsies were used. However, recent data suggest that high definition and chromoendoscopy are better methods of surveillance by improving sensitivity to previously "invisible" flat dysplastic lesions. Management of dysplasia, timing of surveillance, chemoprevention, and the surgical approaches are all areas that stimulate various discussions. The aim of this review is to provide an up-to-date focus on CRC in IBD, from laboratory to bedside.
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Affiliation(s)
- Martina Nebbia
- Colon and Rectal Surgery Division, Humanitas Clinical and Research Center IRCCS, Rozzano, Milano, Italy
| | - Nuha A Yassin
- Colon and Rectal Surgery Division, Humanitas Clinical and Research Center IRCCS, Rozzano, Milano, Italy
| | - Antonino Spinelli
- Colon and Rectal Surgery Division, Humanitas Clinical and Research Center IRCCS, Rozzano, Milano, Italy.,Deparment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy
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Kochar B, Cai W, Cagan A, Ananthakrishnan AN. Pretreatment Frailty Is Independently Associated With Increased Risk of Infections After Immunosuppression in Patients With Inflammatory Bowel Diseases. Gastroenterology 2020; 158:2104-2111.e2. [PMID: 32105728 DOI: 10.1053/j.gastro.2020.02.032] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/13/2020] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Infections are an important adverse effect of immunosuppression for treatment of inflammatory bowel diseases (IBDs). However, risk of infection cannot be sufficiently determined based on patients' ages or comorbidities. Frailty has been associated with outcomes of patients with other inflammatory diseases. We aimed to determine the association between frailty and risk of infections after immunosuppression for IBD. METHODS We performed a cohort study of 11,001 patients with IBD, using a validated frailty definition based on International Classification of Disease codes to identify patients who were frail vs fit in the 2 years before initiation of an anti-tumor necrosis factor (TNF) or immunomodulator therapy, from 1996 through 2010. Our primary outcome was an infection in the first year after treatment. We constructed multivariable logistic regression models, adjusting for clinically pertinent confounders (age, comorbidities, steroid use, and combination therapy) to determine the association between frailty and posttreatment infections. RESULTS There were 1299 patients treated with an anti-TNF agent and 2676 patients treated with an immunomodulator. In this cohort, 5% of patients who received anti-TNF therapy and 7% of patients who received an immunomodulator were frail in the 2 years before immunosuppression. Frail patients were older and had more comorbidities. Higher proportions of frail patients developed infections after treatment (19% after TNF and 17% after immunomodulators) compared with fit patients (9% after TNF and 7% after immunomodulators; P < .01 for frail vs fit in both groups). Frail patients had an increased risk of infection after we adjusted for age, comorbidities, and concomitant medications (anti-TNF adjusted odds ratio, 2.05 [95% confidence interval, 1.07-3.93] and immunomodulator adjusted odds ratio, 1.81 [95% confidence interval, 1.22-2.70]). CONCLUSIONS Frailty was associated with infections after immunosuppression in patients with IBD after we adjust for age and comorbidities. Systematic assessment and strategies to improve frailty might reduce infection risk in patients with IBD.
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Affiliation(s)
- Bharati Kochar
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Clinical Translational Epidemiology Unit, The Mongan Institute, Boston, Massachusetts
| | - Winston Cai
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Clinical Translational Epidemiology Unit, The Mongan Institute, Boston, Massachusetts.
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Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia. Clin Gastroenterol Hepatol 2020; 18:1528-1536.e5. [PMID: 31202983 DOI: 10.1016/j.cgh.2019.05.062] [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: 12/18/2018] [Revised: 04/30/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD. METHODS We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium. In searches of IBD pathology databases, we identified 813 lesions (616 low-grade dysplasias [LGDs], 64 high-grade dysplasias [HGDs], and 133 CACs) in 410 patients with IBD: 299 had dysplasia (73%) and 111 had CAC (27%). The primary aim was to determine the risk of more-advanced lesions after diagnosis of LGD or HGD. RESULTS Of the 287 patients with LGD, 21 (7%) developed more-advanced lesions (HGD or CAC) after a median time period of 86 months (interquartile range, 34-214). Of the 28 patients with HGD, 4 (14%) developed CAC after a median time period of 180 months (interquartile range, 23-444). The overall cumulative incidence of CAC at 10 years after an initial diagnosis of HGD was 24.3% and after an initial diagnosis of LGD was 8.5% (P < .05). Metachronous lesions, non-polypoid lesions, and colonic stricture were associated with risk of occurrence of more-advanced lesions after LGD (P < .05). Of the 630 dysplastic lesions identified during endoscopy, 545 (86%) were removed during the same procedure or during a follow-up endoscopy or by surgery. Of 111 patients with CAC, 95 (86%) did not have prior detection of dysplasia and 64 of these 95 patients (67%) developed CAC outside of the screening or surveillance period recommended by the European Crohn's and Colitis Organisation. CONCLUSIONS In an analysis of pathology data from 7 medical centers in Belgium, we found a low rate of detection of more-advanced lesions following detection of LGD or HGD-taking into account that most of the lesions were removed. Main risk factors for development of more-advanced lesions after LGD were metachronous lesions, non-polypoid lesions, and colon strictures.
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The feasibility of differentiating colorectal cancer from normal and inflammatory thickening colon wall using CT texture analysis. Sci Rep 2020; 10:6346. [PMID: 32286352 PMCID: PMC7156692 DOI: 10.1038/s41598-020-62973-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 03/18/2020] [Indexed: 12/13/2022] Open
Abstract
To investigate the diagnostic value of texture analysis (TA) for differentiating between colorectal cancer (CRC), colonic lesions caused by inflammatory bowel disease (IBD), and normal thickened colon wall (NTC) on computed tomography (CT) and assess which scanning phase has the highest differential diagnostic value. In all, 107 patients with CRC, 113 IBD patients with colonic lesions, and 96 participants with NTC were retrospectively enrolled. All subjects underwent multiphase CT examination, including pre-contrast phase (PCP), arterial phase (AP), and portal venous phase (PVP) scans. Based on these images, classification by TA and visual classification by radiologists were performed to discriminate among the three tissue types. The performance of TA and visual classification was compared. Precise TA classification results (error, 2.03–12.48%) were acquired by nonlinear discriminant analysis for CRC, IBD and NTC, regardless of phase or feature selection. PVP images showed a better ability to discriminate the three tissues by comprising the three scanning phases. TA showed significantly better performance in discriminating CRC, IBD and NTC than visual classification for residents, but there was no significant difference in classification between TA and experienced radiologists. TA could provide useful quantitative information for the differentiation of CRC, IBD and NTC on CT, particularly in PVP images.
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38
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Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study. Lancet Gastroenterol Hepatol 2020; 5:475-484. [PMID: 32066530 DOI: 10.1016/s2468-1253(20)30005-4] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 01/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population. METHODS For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis. FINDINGS During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0·47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0·31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1·74 (1·54-1·96). 499 (0·82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0·64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1·40 (95% CI 1·27-1·53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1·42 [1·16-1·75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0·27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1·40 [1·16-1·68]) or CRC diagnosis (HR 1·12 [0·98-1·28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC. INTERPRETATION Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC. FUNDING Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.
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Machicado JD, Kolb JM, Wani SB. Endoscopic Lesion Recognition and Advanced Imaging Modalities. GASTROINTESTINAL INTERVENTIONAL ENDOSCOPY 2020:3-23. [DOI: 10.1007/978-3-030-21695-5_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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40
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Zhou Q, Shen ZF, Wu BS, Xu CB, He ZQ, Chen T, Shang HT, Xie CF, Huang SY, Chen YG, Chen HB, Han ST. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:5363261. [PMID: 31781191 PMCID: PMC6874962 DOI: 10.1155/2019/5363261] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.
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Affiliation(s)
- Qing Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhao-Feng Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ben-sheng Wu
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Cheng-biao Xu
- Xuyi Hospital of Traditional Chinese Medicine, Huaian, Jiangsu, China
| | - Zhong-qi He
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Tuo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong-tao Shang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao-fan Xie
- Shishi General Hospital, Quanzhou, Fujian, China
| | - Si-yi Huang
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yu-gen Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hai-bo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shu-tang Han
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Chascsa DM, Lindor KD. Cancer risk, screening and surveillance in primary sclerosing cholangitis. MINERVA GASTROENTERO 2019; 65:214-228. [PMID: 31220911 DOI: 10.23736/s1121-421x.19.02586-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.
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Affiliation(s)
- David M Chascsa
- Departments of Gastroenterology and Hepatology and Transplant Center, Mayo Clinic, Phoenix, AZ, USA -
| | - Keith D Lindor
- Office of University Provost, Arizona State University, Phoenix, AZ, USA
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Clarke WT, Feuerstein JD. Colorectal cancer surveillance in inflammatory bowel disease: Practice guidelines and recent developments. World J Gastroenterol 2019; 25:4148-4157. [PMID: 31435169 PMCID: PMC6700690 DOI: 10.3748/wjg.v25.i30.4148] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/14/2019] [Accepted: 07/03/2019] [Indexed: 02/06/2023] Open
Abstract
Patients with long-standing inflammatory bowel disease (IBD) involving at least 1/3 of the colon are at increased risk for colorectal cancer (CRC). Advancements in CRC screening and surveillance and improved treatment of IBD has reduced CRC incidence in patients with ulcerative colitis and Crohn’s colitis. Most cases of CRC are thought to arise from dysplasia, and recent evidence suggests that the majority of dysplastic lesions in patients with IBD are visible, in part thanks to advancements in high definition colonoscopy and chromoendoscopy. Recent practice guidelines have supported the use of chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies. Endoscopists are encouraged to endoscopically resect visible dysplasia and only recommend surgery when a complete resection is not possible. New technologies such as virtual chromoendoscopy are emerging as potential tools in CRC screening. Patients with IBD at increased risk for developing CRC should undergo surveillance colonoscopy using new approaches and techniques.
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Affiliation(s)
- William T Clarke
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Joseph D Feuerstein
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
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Shah SC, Itzkowitz SH. Management of Inflammatory Bowel Disease-Associated Dysplasia in the Modern Era. Gastrointest Endosc Clin N Am 2019; 29:531-548. [PMID: 31078251 PMCID: PMC7354094 DOI: 10.1016/j.giec.2019.02.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article begins with a brief overview of risk factors for colorectal neoplasia in inflammatory bowel disease to concretize the approach to risk stratification. It then provides an up-to-date review of diagnosis and management of dysplasia in inflammatory bowel disease, which integrates new and emerging data in the field. This is particularly relevant in an era of increased attention to cost- and resource-containment from the health systems vantage point, coupled with a heightened prioritization of patient quality of life and shared decision-making. Also provided is a brief discussion of the status of newer therapeutic techniques, such as endoscopic submucosal dissection.
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Affiliation(s)
- Shailja C. Shah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Steven H. Itzkowitz
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Krishnakumar C, Ballengee CR, Liu C, Kim MO, Baker SS, Baldassano RN, Cohen SA, Crandall WV, Denson LA, Dubinsky MC, Evans J, Gokhale R, Griffiths A, Guthery SL, Oliva-Hemker M, Heyman MB, Keljo D, Kellermayer R, Leleiko NS, Mack DR, Markowitz JF, Moulton DE, Noe JD, Otley AR, Patel AS, Pfefferkorn M, Rabizadeh S, Rosh JR, Snapper S, Walters TD, Ziring D, Mondal K, Kappelman MD, Hyams JS, Kugathasan S. Variation in Care in the Management of Children With Crohn's Disease: Data From a Multicenter Inception Cohort Study. Inflamm Bowel Dis 2019; 25:1208-1217. [PMID: 30601983 DOI: 10.1093/ibd/izy363] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Variation in care is common in medical practice. Reducing variation in care is shown to improve quality and increase favorable outcomes in chronic diseases. We sought to identify factors associated with variation in care in children with newly diagnosed Crohn's disease (CD). METHODS Prospectively collected data from a 28-site multicenter inception CD cohort were analyzed for variations in diagnostic modalities, treatment, and follow-up monitoring practices, along with complicated disease outcomes over 3 years in 1046 children. Generalized linear mixed effects models were used to investigate the intercenter variations in each outcome variable. RESULTS The mean age at diagnosis was 12 years, and 25.9% were nonwhite. The number of participants ranged from 5 to 112 per site. No variation existed in the initial diagnostic approach. When medication exposure was analyzed, steroid exposure varied from 28.6% to 96.9% (P < 0.01) within 90 days, but variation was not significant over a 3-year period (P = 0.13). Early anti-tumor necrosis factor (anti-TNF) exposure (within 90 days) varied from 2.1% to 65.7% (P < 0.01), but variation was not significant over a 3-year period (P > 0.99). Use of immunomodulators (IMs) varied among centers both within 90 days (P < 0.01) and during 3 years of follow-up (P < 0.01). A significant variation was seen at the geographic level with follow-up small bowel imaging and colonoscopy surveillance after initial therapy. CONCLUSIONS Intercenter variation in care was seen with the initial use of steroids and anti-TNF, but there was no difference in total 3-year exposure to these drugs. Variation in the initiation and long-term use of IMs was significant among sites, but further research with objective measures is needed to explain this variation of care. Small bowel imaging or repeat colonoscopy in CD patients was not uniformly performed across sites. As our data show the widespread existence of variation in care and disease monitoring at geographic levels among pediatric CD patients, future implementation of various practice strategies may help reduce the variation in care.
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Affiliation(s)
- Chenthan Krishnakumar
- Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Cortney R Ballengee
- Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Chunyan Liu
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Mi-Ok Kim
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California
| | - Susan S Baker
- Department of Digestive Diseases and Nutrition Center, University at Buffalo, Buffalo, New York
| | - Robert N Baldassano
- Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Stanley A Cohen
- Department of Pediatrics, Children's Center for Digestive Health Care, LLC, Atlanta, Georgia
| | - Wallace V Crandall
- Department of Pediatric Gastroenterology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio
| | - Lee A Denson
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Marla C Dubinsky
- Department of Pediatrics, Mount Sinai Hospital, New York, New York
| | - Jonathan Evans
- Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, Florida
| | - Ranjana Gokhale
- Department of Pediatrics, The University of Chicago, Chicago, Illinois
| | - Anne Griffiths
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | | | - Maria Oliva-Hemker
- Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, Maryland
| | - Melvin B Heyman
- Department of Pediatrics, University of California at San Francisco, San Francisco, California
| | - David Keljo
- Department of Gastroenterology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Philadelphia
| | - Richard Kellermayer
- Section of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
| | - Neal S Leleiko
- Department of Pediatrics, Hasbro Children's Hospital, Brown Medical School, Providence, Rhode Island
| | - David R Mack
- Department of Pediatrics, Children's Hospital of Eastern Ontario IBD Centre and University of Ottawa, Ottawa, Ontario, Canada
| | - James F Markowitz
- Department of Pediatrics, Cohen Children's Medical Center of New York, Northwell Health, New Hyde Park, New York
| | - Dedrick E Moulton
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Joshua D Noe
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Anthony R Otley
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Ashish S Patel
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Marian Pfefferkorn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, Indiana
| | - Shervin Rabizadeh
- Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California
| | - Joel R Rosh
- Department of Pediatrics, Goryeb Children's Hospital, Morristown, New Jersey
| | - Scott Snapper
- Department of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Thomas D Walters
- Department of Pediatrics, The University of Chicago, Chicago, Illinois
| | - David Ziring
- Department of Pediatrics, UCLA David Geffen School of Medicine, Los Angeles, California
| | - Kajari Mondal
- Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Michael D Kappelman
- Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jeffrey S Hyams
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, Indiana.,Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut
| | - Subra Kugathasan
- Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia
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45
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Samaan MA, Forsyth K, Segal JP, De Jong D, Vleugels JLA, Elkady S, Kabir M, Campbell S, Kok K, Armstrong DG, Penez L, Arenaza AP, Seward E, Vega R, Mehta S, Rahman F, McCartney S, Bloom S, Patel K, Pollok R, Westcott E, Darakhshan A, Williams A, Koumoutsos I, Ray S, Mawdsley J, Anderson S, Sanderson JD, Dekker E, D'Haens GR, Hart A, Irving PM. Current Practices in Ileal Pouch Surveillance for Patients With Ulcerative Colitis: A Multinational, Retrospective Cohort Study. J Crohns Colitis 2019; 13:735-743. [PMID: 30590513 DOI: 10.1093/ecco-jcc/jjy225] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS There are no universally accepted guidelines regarding surveillance of ulcerative colitis [UC] patients after restorative proctocolectomy and ileal pouch-anal anastomosis [IPAA]. There also exists a lack of validated quality assurance standards for performing pouchoscopy. To better understand IPAA surveillance practices in the face of this clinical equipoise, we carried out a retrospective cohort study at five inflammatory bowel disease [IBD] referral centres. METHODS Records of patients who underwent IPAA for UC or IBD unclassified [IBDU] were reviewed, and patients with <1-year follow-up after restoration of intestinal continuity were excluded. Criteria for determining the risk of pouch dysplasia formation were collected as well as the use of pouchoscopy, biopsies, and completeness of reports. RESULTS We included 272 patients. Median duration of pouch follow-up was 10.5 [3.3-23.6] years; 95/272 [35%] had never undergone pouchoscopy for any indication; 191/272 [70%] had never undergone pouchoscopy with surveillance as the specific indication; and 3/26 [12%] high-risk patients had never undergone pouchoscopy. Two cases of adenocarcinoma were identified, occurring in the rectal cuff of low-risk patients. Patients under the care of surgeons appeared more likely to undergo surveillance, but rates of incomplete reporting were higher among surgeons [78%] than gastroenterologists [54%, p = 0.002]. CONCLUSIONS We observed wide variation in surveillance of UC/IBDU-IPAA patients. In addition, the rate of neoplasia formation among 'low-risk' patients was higher than may have been expected. We therefore concur with previous recommendations that pouchoscopy be performed at 1 year postoperatively, to refine risk-stratification based on clinical factors alone. Reports should document findings in all regions of the pouch and biopsies should be taken.
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Affiliation(s)
- Mark A Samaan
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Katrina Forsyth
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Jonathan P Segal
- Department of Gastroenterology, St Mark's Hospital, London, UK.,Faculty of Medicine, Department of Surgery & Cancer, Imperial College London, London, UK
| | - Djuna De Jong
- Department of Gastroenterology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands
| | - Jasper L A Vleugels
- Department of Gastroenterology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands
| | - Soad Elkady
- Department of Gastroenterology, St Mark's Hospital, London, UK.,Faculty of Medicine, Department of Internal Medicine, Gastroenterology unit, University of Alexandria, Alexandria, Egypt
| | - Misha Kabir
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Samantha Campbell
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Klaartje Kok
- Department of Gastroenterology, Barts Health NHS Foundation Trust, London, UK
| | - David G Armstrong
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Lawrence Penez
- Department of Gastroenterology, St Mark's Hospital, London, UK
| | - Aitor P Arenaza
- Department of Gastroenterology, St Mark's Hospital, London, UK
| | - Edward Seward
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Roser Vega
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Shameer Mehta
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Farooq Rahman
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Sara McCartney
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Stuart Bloom
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Kamal Patel
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Edward Westcott
- Department of Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Amir Darakhshan
- Department of Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Andrew Williams
- Department of Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Ioannis Koumoutsos
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Shuvra Ray
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Joel Mawdsley
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Simon Anderson
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Jeremy D Sanderson
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Evelien Dekker
- Department of Gastroenterology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands
| | - Geert R D'Haens
- Department of Gastroenterology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands
| | - Ailsa Hart
- Department of Gastroenterology, St Mark's Hospital, London, UK.,Faculty of Medicine, Department of Surgery & Cancer, Imperial College London, London, UK
| | - Peter M Irving
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
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46
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Verdon C, Aruljothy A, Lakatos PL, Bessissow T. Endoscopic surveillance strategies for dysplasia in ulcerative colitis. Frontline Gastroenterol 2019; 11:124-132. [PMID: 32133111 PMCID: PMC7043085 DOI: 10.1136/flgastro-2018-101056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 03/11/2019] [Accepted: 03/17/2019] [Indexed: 02/04/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with an increased risk of colorectal cancer (CRC). This has led to the implementation of surveillance programmes to minimise this risk. Overall, these proactive programmes in association with better medical therapies have reduced the incidence of CRC in this population. Specific populations remain at increased risk, such as younger age at diagnosis, primary sclerosing cholangitis, colonic strictures and pseudopolyps. The majority of gastrointestinal international societies favour chromoendoscopy with targeted biopsies or random biopsies. The aim of this review is to present the current literature on dysplasia surveillance, the methodology and endoscopic technology available to assess dysplasia in UC.
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Affiliation(s)
- Christine Verdon
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
| | - Achuthan Aruljothy
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada
| | - Peter L Lakatos
- Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada,1st Department of Medicine, Semmelweis University, Budapest, Hungary
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47
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Kisiel JB, Klepp P, Allawi HT, Taylor WR, Giakoumopoulos M, Sander T, Yab TC, Moum BA, Lidgard GP, Brackmann S, Mahoney DW, Roseth A, Ahlquist DA. Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-Grade Dysplasia in Patients With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2019; 17:914-921.e5. [PMID: 29775793 PMCID: PMC6368476 DOI: 10.1016/j.cgh.2018.05.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 03/08/2018] [Accepted: 05/07/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. METHODS We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. RESULTS Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied. CONCLUSIONS In an analysis of stool samples from 3 independent studies of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance.
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Affiliation(s)
- John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
| | - Pasquale Klepp
- Department of Internal Medicine, Lovisenberg Hospital, Oslo, Norway; Clinical Medicine, University Hospital, University of Oslo, Oslo, Norway
| | - Hatim T Allawi
- Department of Gastroenterology, Akershus University Hospital, University of Oslo, Oslo, Norway
| | - William R Taylor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Tracy C Yab
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Bjorn A Moum
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | | | - Stephan Brackmann
- Department of Gastroenterology, Akershus University Hospital, University of Oslo, Oslo, Norway; Clinical Medicine, University Hospital, University of Oslo, Oslo, Norway
| | - Douglas W Mahoney
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Arne Roseth
- Department of Internal Medicine, Lovisenberg Hospital, Oslo, Norway
| | - David A Ahlquist
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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48
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Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol 2019; 114:384-413. [PMID: 30840605 DOI: 10.14309/ajg.0000000000000152] [Citation(s) in RCA: 937] [Impact Index Per Article: 156.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
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Affiliation(s)
- David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Crohn's and Colitis Center, Massachusetts General Hospital, Boston, MA, USA
| | - Corey A Siegel
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Bryan G Sauer
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Millie D Long
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
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49
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Surveillance Colonoscopy for Ulcerative Colitis-Associated Colorectal Cancer Offers Better Overall Survival in Real-World Surgically Resected Cases. Am J Gastroenterol 2019; 114:483-489. [PMID: 30747769 DOI: 10.14309/ajg.0000000000000117] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia. METHODS Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (<8 years after UC onset) were identified. The distribution of CRC lesions was also assessed. RESULTS Cancer stages were significantly more advanced in the non-SC group than in the SC group (P < 0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (<8 years) (P < 0.01; AUC: 0.85). The most common sites of CRC were the rectum (51%) and sigmoid colon (20%). Multiple CRC was identified in 16% of patients. CONCLUSIONS Surveillance colonoscopy was effective and improved the OS in patients with UC. We recommend that patients with late-onset UC (>40 years) undergo SCs earlier because of the high incidence of CRC within 8 years of UC onset. Moreover, the rectum and sigmoid colon should be more thoroughly examined.
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50
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East JE, Boyapati RK, Torres J, Parker CE, MacDonald JK, Chande N, Feagan BG. Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews. Inflamm Bowel Dis 2019; 25:472-478. [PMID: 30789982 DOI: 10.1093/ibd/izy268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Indexed: 12/09/2022]
Abstract
A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.
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Affiliation(s)
- James E East
- Translational Gastroenterology Unit and Oxford NIHR Biomedical Research Centre, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | - Ray K Boyapati
- Department of Gastroenterology, Monash Health, Melbourne, Victoria, Australia
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.,Hospital Beatriz Ângelo, Gastroenterology Division, Loures, Portugal
| | | | - John K MacDonald
- Cochrane IBD Group, University of Western Ontario, London, Ontario, Canada
| | - Nilesh Chande
- Cochrane IBD Group, University of Western Ontario, London, Ontario, Canada.,Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - Brian G Feagan
- Robarts Clinical Trials Inc. London, Ontario, Canada.,Cochrane IBD Group, University of Western Ontario, London, Ontario, Canada.,Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
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