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Rennebaum F, Demmig C, Schmidt HH, Vollenberg R, Tepasse PR, Trebicka J, Gu W, Ullerich H, Kabar I, Cordes F. Elevated Liver Fibrosis Progression in Isolated PSC Patients and Increased Malignancy Risk in a PSC-IBD Cohort: A Retrospective Study. Int J Mol Sci 2023; 24:15431. [PMID: 37895106 PMCID: PMC10607359 DOI: 10.3390/ijms242015431] [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: 09/23/2023] [Revised: 10/18/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited. We aimed to analyze the clinical disease course of PSC patients without IBD compared to PSC patients with UC and CD, respectively. A retrospective data analysis of patients with isolated PSC (n = 41) and of patients with concomitant IBD (n = 115) was performed. In detail, PSC disease characteristics including occurrence of dominant stenoses, liver cirrhosis, OLT and malignancy, as well as the temporal course of PSC activity and disease progression, were analyzed. A multivariable Cox regression model and a Fine-Gray competing risk model were further used for the independent risk factor analysis of cirrhosis development and OLT. Patients with isolated PSC were significantly older at first diagnosis than patients with PSC-IBD (39 vs. 28 years, p = 0.02). A detailed analysis of the course of PSC revealed a faster PSC progression after initial diagnosis in isolated PSC patients compared to PSC-IBD including significantly earlier diagnosis of dominant stenoses (29 vs. 74 months, p = 0.021) and faster progression to liver cirrhosis (38 vs. 103 months, p = 0.027). Patients with isolated PSC have a higher risk of developing cirrhosis than patients with PSC-IBD (Gray's test p = 0.03). OLT was more frequently performed in male patients with isolated PSC compared to males with coincident IBD (48% (n = 13) vs. 33% (n = 25), p = 0.003). Colorectal carcinoma was significantly more often diagnosed in patients with PSC-IBD than in isolated PSC (8.7% vs. 0%, p = 0.042). Patients with isolated PSC seem to have a different clinical course of disease than PSC patients with concomitant IBD characterized by a more pro-fibrotic disease course with earlier onset of liver cirrhosis and dominant stenosis but with less malignancy. These data may be interpreted as either a more progressive disease course of isolated PSC or a later diagnosis of the disease at an advanced disease stage. The different clinical courses of PSC and the underlying mechanisms of the gut-liver axis need further attention.
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Affiliation(s)
- Florian Rennebaum
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Claudia Demmig
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Hartmut H. Schmidt
- Department of Hepatology, Gastroenterology and Transplantation Medicine, University Hospital Essen, 45147 Essen, Germany;
| | - Richard Vollenberg
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Phil-Robin Tepasse
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Jonel Trebicka
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Wenyi Gu
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Hansjoerg Ullerich
- Department of Internal Medicine B, Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, 48149 Münster, Germany; (C.D.); (R.V.); (P.-R.T.); (J.T.); (W.G.); (H.U.)
| | - Iyad Kabar
- Department of Internal Medicine, University Teaching Hospital Raphaelsklinik Münster, 48143 Münster, Germany;
| | - Friederike Cordes
- Department of Internal Medicine II Gastroenterology, University Teaching Hospital Euregio-Klinik Nordhorn, 48527 Nordhorn, Germany;
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Hsiao SW, Yen HH, Chen YY. Chemoprevention of Colitis-Associated Dysplasia or Cancer in Inflammatory Bowel Disease. Gut Liver 2022; 16:840-848. [PMID: 35670121 PMCID: PMC9668496 DOI: 10.5009/gnl210479] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/20/2021] [Accepted: 12/07/2021] [Indexed: 08/27/2023] Open
Abstract
The association between inflammatory bowel disease and colorectal cancer is well known. Although the overall incidence of inflammatory bowel disease has declined recently, patients with this disease still have a 1.7-fold increased risk of colorectal cancer. The risk factors for developing colorectal cancer include extensive colitis, young age at diagnosis, disease duration, primary sclerosing cholangitis, chronic colonic mucosal inflammation, dysplasia lesion, and post-inflammatory polyps. In patients with inflammatory bowel disease, control of chronic inflammation and surveillance colonoscopies are important for the prevention of colorectal cancer. The 2017 guidelines from the European Crohn's and Colitis Organisation suggest that colonoscopies to screen for colorectal cancer should be performed when inflammatory bowel disease symptoms have lasted for 8 years. Current evidence supports the use of chemoprevention therapy with mesalamine to reduce the risk of colorectal cancer in patients with ulcerative colitis. Other compounds, including thiopurine, folic acid, statin, and tumor necrosis factor-α inhibitor, are controversial. Large surveillance cohort studies with longer follow-up duration are needed to evaluate the impact of drugs on colorectal cancer risks.
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Affiliation(s)
- Shun-Wen Hsiao
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- General Education Center, Chienkuo Technology University, Changhua, Taiwan
- Department of Electrical Engineering, Chung Yuan Christian University, Taoyuan, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, Taiwan
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Aranake-Chrisinger J, Dassopoulos T, Yan Y, Nalbantoglu ILK. Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation. World J Gastroenterol 2020; 26:4126-4139. [PMID: 32821074 PMCID: PMC7403798 DOI: 10.3748/wjg.v26.i28.4126] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/08/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) associated inflammatory bowel disease (IBD) is a unique form of IBD (PSC-IBD) with distinct clinical and histologic features from ulcerative colitis (UC) and Crohn disease (CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other.
AIM To study the histologic and clinical features of PSC patients with and without IBD.
METHODS We assessed specimens from patients with UC (n = 28), CD (n = 10), PSC and UC (PSC-UC; n = 26); PSC and CD (PSC-CD; n = 6); and PSC and no IBD (PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation (OLT) were noted.
RESULTS PSC-UC patients had more isolated right-sided disease (P = 0.03), and less active inflammation in left colon, rectum (P = 0.03 and P = 0.0006), and overall (P = 0.0005) compared to UC. They required less steroids (P = 0.01) and fewer colectomies (P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC (P = 0.1). PSC-IBD (PSC-UC and PSC-CD) patients with OLT had severe disease in the left colon and rectum (P = 0.04).
CONCLUSION PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.
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Affiliation(s)
- John Aranake-Chrisinger
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | | | - Yan Yan
- Departments of Surgery and Biostatistics, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | - ILKe Nalbantoglu
- Department of Anatomic Pathology, Yale University School of Medicine, New Haven, CT 06525, United States
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
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Ansell J, Grass F, Merchea A. Surgical Management of Dysplasia and Cancer in Inflammatory Bowel Disease. Surg Clin North Am 2019; 99:1111-1121. [PMID: 31676051 DOI: 10.1016/j.suc.2019.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Patients with inflammatory bowel disease are at an increased risk of cancer secondary to long-standing intestinal inflammation. Surgical options must take into account the significant risk of synchronous disease at other colonic sites. Ileal pouch anal anastomosis is a viable option for patients with ulcerative colitis, but this should be restricted to early cancers that are unlikely to require preoperative or postoperative radiation treatment.
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Affiliation(s)
- James Ansell
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Fabian Grass
- Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Amit Merchea
- Division of Colon and Rectal Surgery, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA.
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Samadder NJ, Valentine JF, Guthery S, Singh H, Bernstein CN, Leighton JA, Wan Y, Wong J, Boucher K, Pappas L, Rowe K, Burt RW, Curtin K, Smith KR. Family History Associates With Increased Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2019; 17:1807-1813.e1. [PMID: 30267862 DOI: 10.1016/j.cgh.2018.09.038] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 09/10/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing colorectal cancer (CRC). Although family history of CRC is a well-established risk factor in healthy individuals, its role in patients with IBD is less clear. We aimed to estimate the risk of CRC in a cohort of patients with IBD from Utah and the significance of family history of CRC in a first-degree relative (FDR). METHODS We identified Utah residents with IBD, using the Intermountain Healthcare and University of Utah Health Sciences databases, from January 1, 1996, through December 31, 2011. CRCs were identified using the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. CRC incidence was compared with that of the state population by standardized incidence ratios (SIRs). RESULTS A cohort of 9505 individuals with IBD was identified and 101 developed CRC during the study period. The SIR for CRC in patients with Crohn's disease was 3.4 (95% CI, 2.3-4.4), and in patients with ulcerative colitis was 5.2 (95% CI, 3.9-6.6). Patients with IBD and a concurrent diagnosis of primary sclerosing cholangitis had the greatest risk of CRC (SIR, 14.8; 95% CI, 8.3-21.2). A history of CRC in a FDR was associated with a nearly 8-fold increase in risk of CRC in patients with IBD (SIR, 7.9; 95% CI, 1.6-14.3), compared with the state population. CONCLUSIONS Patients with IBD have a 3- to 5-fold increase in risk of CRC, and those with CRC in a FDR have an almost 8-fold increase in risk. Family history may act as a simple measure to identify individuals with IBD at highest risk for CRC and indicates the need for enhanced surveillance in this population.
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Affiliation(s)
- N Jewel Samadder
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Phoenix, Arizona; Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, Utah.
| | - John F Valentine
- Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, Utah
| | - Stephen Guthery
- Department of Pediatrics (Gastroenterology), University of Utah, Salt Lake City, Utah
| | - Harminder Singh
- University of Manitoba IBD Clinical and Research Centre, Division of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Centre, Division of Gastroenterology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Jonathan A Leighton
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Phoenix, Arizona
| | - Yuan Wan
- Department of Pedigree and Population Resource, University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Jathine Wong
- Department of Pedigree and Population Resource, University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Kenneth Boucher
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Epidemiology), University of Utah, Salt Lake City, Utah
| | - Lisa Pappas
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Kerry Rowe
- Department of Bioinformatics, Intermountain Healthcare, Salt Lake City, Utah
| | - Randall W Burt
- Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah
| | - Karen Curtin
- Department of Pedigree and Population Resource, University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Genetic Epidemiology), University of Utah, Salt Lake City, Utah
| | - Ken R Smith
- Department of Pedigree and Population Resource, University of Utah, Salt Lake City, Utah; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Family and Consumer Studies, University of Utah, Salt Lake City, Utah
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Wen KW, Rabinovitch PS, Wang D, Huang D, Mattis AN, Choi WT. Utility of DNA Flow Cytometric Analysis of Paraffin-embedded Tissue in the Risk Stratification and Management of 'Indefinite for dysplasia' in Patients With Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:472-481. [PMID: 30423034 DOI: 10.1093/ecco-jcc/jjy193] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [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 The clinical significance of 'indefinite for dysplasia' [IND] in patients with inflammatory bowel disease remains unclear. Currently, no biomarker can reliably differentiate reactive changes from true dysplasia and/or risk stratify IND. METHODS A total of 52 IND colon biopsies were analysed by DNA flow cytometry. The follow-up result of each biopsy was determined by reviewing all subsequent biopsies and endoscopic reports for the occurrence of high-grade dysplasia [HGD] or colorectal cancer [CRC] at the site of previous biopsy or in the same segment of colon. RESULTS The overall 1-, 3-, 5-, and 7-year detection rates of HGD or CRC in all 52 IND cases were 4.6% (95% confidence interval [CI], 0.0%-10.6%), 18.2% [95% CI, 3.5%-30.7%], 26.3% [95% CI, 8.4%-40.7%], and 31.6% [95% CI, 11.2%-47.4%], respectively. More interestingly, 10.6% of IND cases with aneuploidy were subsequently found to have HGD or CRC within 1 year [95% CI, 0.0%-23.7%], with 36.4% [95% CI, 7.1%-56.5%], 51.7% [95% CI, 16.1%-72.2%], and 59.8% [95% CI, 21.4%-79.5%] detected within 3, 5, and 7 years, respectively. By comparison, in the setting of normal DNA content, 1-, 3-, 5-, and 7-year detection rates of HGD or CRC were 0.8% [95% CI, 0.0%-2.7%], 3.3% [95% CI, 0.0%-9.6%], 5.2% [95% CI, 0.0%-14.7%], and 6.5% [95% CI, 0.0%-18.1%], respectively. Only the presence of aneuploidy was found to be a significant predictor of HGD or CRC with the estimated univariate and multivariate hazard ratios of 13.8 [p = 0.016] and 50.3 [p = 0.010], respectively. CONCLUSIONS IND may not be a low-risk condition for HGD or CRC. In this regard, the presence of aneuploidy can identify a subset of IND cases that are at increased risk for subsequent detection of HGD or CRC.
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Affiliation(s)
- Kwun Wah Wen
- University of California at San Francisco, Department of Pathology, San Francisco, CA, USA
| | | | - Dongliang Wang
- SUNY Upstate Medical University, Department of Public Health and Preventive Medicine, Syracuse, NY, USA
| | - Danning Huang
- SUNY Upstate Medical University, Department of Public Health and Preventive Medicine, Syracuse, NY, USA
| | - Aras N Mattis
- University of California at San Francisco, Department of Pathology, San Francisco, CA, USA
| | - Won-Tak Choi
- University of California at San Francisco, Department of Pathology, San Francisco, CA, USA
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Lopez A, Pouillon L, Beaugerie L, Danese S, Peyrin-Biroulet L. Colorectal cancer prevention in patients with ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33:103-109. [PMID: 30060933 DOI: 10.1016/j.bpg.2018.05.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 05/10/2018] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis is characterized by chronic inflammation, which may lead to the accumulation of high levels of pro-inflammatory cytokines within the colonic mucosa, and thus to dysplastic lesions and cancer. Although the trend is decreasing, ulcerative colitis patients still have a 2.4 fold higher risk of colorectal cancer compared to the general population. The key task is to control colonic inflammation, and a rapid step-up approach while closely monitoring intestinal inflammation are recommented. Surveillance colonoscopy program demonstrated its efficacy for reducing the incidence of colorectal cancer in ulcerative colitis. The impact of medication on the reduction of colorectal cancer risk was hardly investigated and it remains unclear whether they have intrinsic anti-neoplastic properties or only downregulate inflammatory pathways. Several studies showed a decreased risk of colorectal cancer in ulcerative colitis patients treated with 5-aminosalicylic acid and chemoprevention with mesalamine compounds is currently recommended. The current level of evidence is too low for thiopurines and anti-TNFα agents. Large, prospective cohort studies are ongoing and are likely to bring new findings about the impact of drugs on colorectal cancer risk in the current era of biologics.
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Affiliation(s)
- Anthony Lopez
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.
| | - Lieven Pouillon
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France; Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Imeldalaan, Bonheiden, Belgium
| | - Laurent Beaugerie
- Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine, F-75012, France; ERL 1057 INSERM/UMRS 7203, UPMC University, Paris, 06F-75005, Paris, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
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Cabrera JM, Sato TT. Medical and Surgical Management of Pediatric Ulcerative Colitis. Clin Colon Rectal Surg 2018; 31:71-79. [PMID: 29487489 PMCID: PMC5825852 DOI: 10.1055/s-0037-1609021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Inflammatory bowel disease (IBD) describes a spectrum of idiopathic, lifelong, and progressive intestinal inflammatory conditions that includes Crohn's disease, ulcerative colitis, and indeterminate colitis. A worldwide increase in the incidence of IBD has been observed. In comparison to adults, IBD occurring during childhood and adolescence has several unique clinical characteristics and surgical management issues. In this article, we provide an overview contrasting these important differences.
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Affiliation(s)
- José M. Cabrera
- Division of Pediatric Gastroenterology, Department of Pediatrics, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Thomas T. Sato
- Division of Pediatric Surgery, Department of Surgery, Children's Hospital of Wisconsin, Medical College of Wisconsin, Children's Corporate Center, Milwaukee, Wisconsin
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Jewel Samadder N, Valentine JF, Guthery S, Singh H, Bernstein CN, Wan Y, Wong J, Boucher K, Pappas L, Rowe K, Bronner M, Ulrich CM, Burt RW, Curtin K, Smith KR. Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah. Dig Dis Sci 2017; 62:2126-2132. [PMID: 28050782 DOI: 10.1007/s10620-016-4435-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 12/21/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The molecular, endoscopic, and histological features of IBD-associated CRC differ from sporadic CRC. The objective of this study was to describe the prevalence, clinical features, and prognosis of IBD-associated CRC compared to patients with sporadic CRC in a US statewide population-based cohort. METHODS All newly diagnosed cases of CRC between 1996 and 2011 were obtained from Utah Cancer Registry. IBD was identified using a previously validated algorithm, from statewide databases of Intermountain Healthcare, University of Utah Health Sciences, and the Utah Population Database. Logistic regression was performed to identify risk factors associated with IBD-associated cancer and Cox regression for differences in survival. RESULTS Among 12,578 patients diagnosed with CRC, 101 (0.8%) had a prior history of IBD (61 ulcerative colitis and 40 Crohn's disease). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (67.1 vs 52.8 years, P < 0.001). Individuals with IBD-associated CRC were more likely to be men (odds ratio [OR] 1.90, 95% CI 1.23-2.92), aged less than 65 years (OR 6.77, 95% CI 4.06-11.27), and have CRC located in the proximal colon (OR 2.79, 95% CI 1.85-4.20) than those with sporadic CRC. Nearly 20% of the IBD-associated CRCs had evidence of primary sclerosing cholangitis. After adjustment for age, gender, and stage at diagnosis, the excess hazard of death after CRC diagnosis was 1.7 times higher in IBD than in non-IBD patients (95% CI 1.27-2.33). CONCLUSIONS The features of patients with CRC and IBD differ significantly from those without IBD and may be associated with increased mortality.
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Affiliation(s)
- N Jewel Samadder
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA. .,Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, UT, USA.
| | - John F Valentine
- Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, UT, USA
| | - Stephen Guthery
- Department of Pediatrics (Gastroenterology), University of Utah, Salt Lake City, UT, USA
| | - Harminder Singh
- Department of Internal Medicine (Gastroenterology), University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Charles N Bernstein
- Department of Internal Medicine (Gastroenterology), University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB, Canada
| | - Yuan Wan
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Pedigree and Population Resource, University of Utah, Salt Lake City, UT, USA
| | - Jathine Wong
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Pedigree and Population Resource, University of Utah, Salt Lake City, UT, USA
| | - Kenneth Boucher
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Medicine (Epidemiology), University of Utah, Salt Lake City, UT, USA
| | - Lisa Pappas
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA
| | - Kerry Rowe
- Department of Bioinformatics, Intermountain Healthcare, Salt Lake City, UT, USA
| | - Mary Bronner
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
| | - Cornelia M Ulrich
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Population Sciences, University of Utah, Salt Lake City, UT, USA
| | - Randall W Burt
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, UT, USA.,Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA
| | - Karen Curtin
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Medicine (Genetic Epidemiology), University of Utah, Salt Lake City, UT, USA.,Department of Pedigree and Population Resource, University of Utah, Salt Lake City, UT, USA
| | - Ken R Smith
- Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.,Department of Population Sciences, University of Utah, Salt Lake City, UT, USA.,Department of Family and Consumer Studies, University of Utah, Salt Lake City, UT, USA.,Department of Pedigree and Population Resource, University of Utah, Salt Lake City, UT, USA
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1257] [Impact Index Per Article: 157.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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11
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Yamamoto-Furusho J, Bosques-Padilla F, Daffra P, De Paula J, Etchevers J, Galiano M, Ibañez P, Juliao F, Kotze P, Marroquín de la Garza J, Monreal Robles R, Rocha J, Steinwurz F, Vázquez-Frías R, Veitia G, Zaltman C. Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2017. [DOI: 10.1016/j.rgmxen.2016.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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12
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Yamamoto-Furusho JK, Bosques-Padilla F, Daffra P, De Paula JA, Etchevers J, Galiano MT, Ibañez P, Juliao F, Kotze PG, Marroquín de la Garza JM, Monreal Robles R, Rocha JL, Steinwurz F, Vázquez-Frías R, Veitia G, Zaltman C. Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). REVISTA DE GASTROENTEROLOGIA DE MEXICO 2017; 82:134-155. [PMID: 28318706 DOI: 10.1016/j.rgmx.2016.07.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 07/18/2016] [Accepted: 07/21/2016] [Indexed: 12/15/2022]
Abstract
This is the first Latin American Consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) regarding special situations in patients with inflammatory bowel disease (IBD). The aim of this consensus is to raise awareness in the medical community in all Latin American countries with respect to pregnancy, vaccinations, infections, neoplasms, including colorectal cancer, and pediatric issues in patients with IBD.
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Affiliation(s)
- J K Yamamoto-Furusho
- Clínica de Enfermedad Inflamatoria Intestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
| | - F Bosques-Padilla
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - P Daffra
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - J A De Paula
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - J Etchevers
- Servicio de Gastroenterología, Hospital Italiano, Buenos Aires, Argentina
| | - M T Galiano
- Clínica de Enfermedad Inflamatoria Intestinal, Clínica Marly, Bogotá, Colombia
| | - P Ibañez
- Programa de Enfermedad Inflamatoria Intestinal, Departamento de Gastroenterología, Clínica Las Condes, Santiago, Chile
| | - F Juliao
- Clínica de Enfermedad Inflamatoria Intestinal, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - P G Kotze
- Hospital Universitario Cajuru, Universidad Católica del Paraná (PUCPR), Curitiba, Brasil
| | - J M Marroquín de la Garza
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - R Monreal Robles
- Servicio de Gastroenterología, Hospital Universitario Dr. José Eleuterio González, Universidad Autónoma de Nuevo León, Monterrey, México; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, México
| | - J L Rocha
- Grupo Académico y de Investigación en Crohn y Colitis Ulcerosa Crónica Idiopática de México, Ciudad de México, México
| | - F Steinwurz
- Hospital Israelita Albert Einstein, São Paulo, Brasil
| | - R Vázquez-Frías
- Departamento de Gastroenterología Pediátrica, Hospital Infantil de México Federico Gómez, Ciudad de México, México
| | - G Veitia
- Servicio de Gastroenterología, Hospital Vargas, Caracas, Venezuela
| | - C Zaltman
- Servicio de Gastroenterología, Hospital Clementino Fraga Filho, Departamento de Medicina Interna, Universidad Federal do Rio de Janeiro (UFRJ), Río de Janeiro, Brasil
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13
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Kuzu UB, Ödemiş B, Suna N, Yıldız H, Parlak E, Dişibeyaz S, Torun S, Akpınar MY, Coşkun O, Turhan N, Yüksel M, Kayaçetin E. The Detection of Cholangiocarcinoma in Primary Sclerosing Cholangitis Patients: Single Center Experience. J Gastrointest Cancer 2016; 47:8-14. [PMID: 26537791 DOI: 10.1007/s12029-015-9777-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. Cholangiocarcinoma (CCA) is one of the feared complications of PSC. In our study, we aim to establish the success of brush cytology and CA 19-9 in putting the diagnosis of CCA. METHODS The data of 30 PSC patients was retrospectively screened whom had brush cytology performed due to dominant strictures. The definitive diagnosis was established by histopathological examination or via radiological/clinic follow-up for at least 12 months. RESULTS A total of four patients were excluded from the study. Twenty-six patients diagnosed with PSC, six of which were also diagnosed with CCA, were included in the study. The sensitivity and the specificity of the brush cytology in the diagnosis of CCA in PSC patients were 66.7 and 95%, respectively. CA 19-9 had high correlation with bilirubin level. The optimal level of CA 19-9 in the diagnosis of CCA was determined to be 138.5 U/ml. Superiority of Ramage scoring over CA 19-9 in the diagnosis of CCA in PSC patients was not established (sensitivity and specificity were 50%, 94.7% and 83.3%, 85%, respectively). CONCLUSION Brush cytology has moderate sensitivity in differentiating strictures in PSC patients. CA 19-9 has high sensitivity but bilirubin level can affect the CA 19-9. Therefore, advanced techniques and parameters are needed for detecting CCA in PSC patients.
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Affiliation(s)
- Ufuk Barış Kuzu
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey.
| | - Bülent Ödemiş
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Nuretdin Suna
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Hakan Yıldız
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Erkan Parlak
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Selçuk Dişibeyaz
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Serkan Torun
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Muhammet Yener Akpınar
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Orhan Coşkun
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Nesrin Turhan
- Department of Pathology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Mahmut Yüksel
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
| | - Ertuğrul Kayaçetin
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Education and Research Hospital, Sıhhiye, Ankara, Turkey
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Pattern of Inflammation on Surveillance Colonoscopy Does Not Predict Development of Colitis-associated Neoplasia. Inflamm Bowel Dis 2016; 22:2221-8. [PMID: 27542134 DOI: 10.1097/mib.0000000000000862] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Identification of colonoscopic features which increase colitis-associated neoplasia risk in patients with ulcerative colitis (UC) may allow patient risk stratification. Our objective was to investigate whether colonoscopic features correlate with the risk of developing colitis-associated neoplasia in patients with UC on surveillance. METHODS In this retrospective case-control study, patients with UC who underwent surveillance colonoscopies from 1998 to 2011 were included. Patients with UC with neoplasia were compared with a matched control group of patients with UC without neoplasia in a 1:3 ratio. RESULTS A total of 111 eligible patients with UC with colon neoplasia were compared with 356 patients with UC without colon neoplasia. On univariate analysis, colitis-associated neoplasia was associated with male gender (odds ratio [OR] = 2.58, 95% confidence interval [CI]: 1.71-3.89, P ≤ 0.001) and smoking history (OR = 1.62, 95% CI: 1.1-2.39, P = 0.045) but not with colonoscopic features, including tubular colon/shortened colon, scarring, segment of severe inflammation, inflammatory polyps, colonic stricture, or macroscopically normal appearance colonoscopy. In multivariate analysis, only male gender (OR = 2.68, 95% CI: 1.77-4.08, P ≤ 0.001) was found to be associated with an increased risk, whereas the use of 5-aminosalicylates was associated with a decreased risk for colitis-associated neoplasia (OR = 0.51, 95% CI: 0.31-0.84, P = 0.009). CONCLUSIONS In patients with UC, colonoscopic features especially on standard-definition white-light colonoscopy did not appear to reliably predict the development of colitis-associated neoplasia. This will leave room for image-enhanced endoscopy technology and molecular markers for the early and accurate detection of colitis-associated neoplasia.
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15
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Risk and Surveillance of Cancers in Primary Biliary Tract Disease. Gastroenterol Res Pract 2016; 2016:3432640. [PMID: 27413366 PMCID: PMC4930812 DOI: 10.1155/2016/3432640] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 04/14/2016] [Accepted: 05/18/2016] [Indexed: 12/20/2022] Open
Abstract
Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases.
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16
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Gasia MF, Ghosh S, Panaccione R, Ferraz JG, Kaplan GG, Leung Y, Novak KL, Seow CH, Iacucci M. Targeted Biopsies Identify Larger Proportions of Patients With Colonic Neoplasia Undergoing High-Definition Colonoscopy, Dye Chromoendoscopy, or Electronic Virtual Chromoendoscopy. Clin Gastroenterol Hepatol 2016; 14:704-12.e4. [PMID: 26804384 DOI: 10.1016/j.cgh.2015.12.047] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 12/05/2015] [Accepted: 12/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS It is unclear what are the best and most appropriate endoscopic procedures for detecting colonic neoplasia in patients with long-term colonic inflammatory bowel disease (IBD). Dye chromoendoscopy (DCE) is the standard used in IBD surveillance colonoscopies. However, studies are needed to determine the optimal endoscopic technique for detecting dysplastic lesions. We investigated current practices used in surveillance colonoscopies by IBD gastroenterologists at a single tertiary center. We also determined the rate of neoplasia detection among different surveillance endoscopic techniques in an analysis of random or targeted biopsies. METHODS We collected data on 454 patients with IBD (54.5% male; mean age, 50 y; mean disease duration, 14.5 y; 55.9% with ulcerative colitis, 42.7% with Crohn's disease, and 1.3% with indeterminate colitis) who underwent surveillance colonoscopy from April 2011 through March 2014 at the University of Calgary in Canada. Subjects were examined using white-light standard-definition endoscopy (WLE), high-definition (HD) colonoscopy, virtual electronic chromoendoscopy (VCE), or DCE; random or targeted biopsy specimens were collected. Endoscopic and histologic descriptions with suspected neoplasia were recorded. Rates of neoplasia detection by the different endoscopic procedures were compared using chi-square analysis. RESULTS Of the patients analyzed, 27.7% had WLE endoscopy with random collection of biopsy specimens, 27.3% had HD colonoscopy with random collection of biopsy specimens, 14.1% had VCE with random collection of biopsy specimens, 0.9% had DCE with random collection of biopsy specimens, 12.8% had HD colonoscopy with collection of targeted biopsy specimens, 11.9% had VCE with collection of targeted biopsy specimens, and 5.3% had DCE with collection of targeted biopsy specimens. Neoplastic lesions were detected in 8.2% of the procedures performed in the random biopsy group (95% confidence interval, 5.6-11.7) and 19.1% of procedures in the targeted biopsy group (95% confidence interval, 13.4-26.5) (P < .001). Neoplasias were detected in similar proportions of patients by HD colonoscopy, VCE, or DCE, with targeted biopsy collection. CONCLUSIONS In a large cohort of IBD patients undergoing surveillance colonoscopy, targeted biopsies identified greater proportions of subjects with neoplasia than random biopsies. Targeted collection of biopsy specimens appears to be sufficient for detecting colonic neoplasia in patients undergoing HD colonoscopy, DCE, or VCE, but not WLE.
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Affiliation(s)
- Miriam F Gasia
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Subrata Ghosh
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Remo Panaccione
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Jose G Ferraz
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Gilaad G Kaplan
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Yvette Leung
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Kerri L Novak
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Cynthia H Seow
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada
| | - Marietta Iacucci
- Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada.
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Fevery J, Van Steenbergen W, Van Pelt J, Laleman W, Hoffman I, Geboes K, Vermeire S, Nevens F. Patients with large-duct primary sclerosing cholangitis and Crohn's disease have a better outcome than those with ulcerative colitis, or without IBD. Aliment Pharmacol Ther 2016; 43:612-20. [PMID: 26748470 DOI: 10.1111/apt.13516] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 04/17/2015] [Accepted: 12/13/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Approximately 20% of primary sclerosing cholangitis (PSC) patients with concomitant inflammatory bowel disease (IBD) have Crohn's disease (CD). AIM To compare PSC/CD with other PSC patients. METHODS Retrospective study of 240 PSC patients diagnosed between 1975 and 2012 (median follow-up 12 years). Activity of PSC at diagnosis was assessed by liver biopsy, Mayo risk and ERC scores. Survival without liver transplantation, number of transplantations and liver-related death were endpoints. RESULTS Sixty-three per cent of patients had IBD: 105 UC, 32 CD and 14 IBD unclassified (IBDu). IBD was diagnosed before PSC in 50%. The yearly development of PSC after diagnosing IBD was similar in UC, CD or IBDu. Small-duct PSC was present in 28% of PSC/CD compared to 3% of PSC/UC. Small-duct PSC had a markedly better survival than large-duct PSC: no patient developed cholangiocarcinoma or liver-related death, but colorectal cancer occurred in three patients. In large-duct PSC, a more favourable outcome was evident in patients with CD. The liver disease was less progressive: one patient underwent liver transplantation compared to 28% and liver-related deaths were absent compared to 7% in the other PSC groups. CONCLUSIONS The prevalence of PSC with concomitant Crohn's disease is relatively rare, but the outcome is more benign than PSC with UC or without IBD. Approximately one-fourth has small-duct PSC. In large-duct PSC/CD, liver disease is less aggressive and the outcome is much better. The outcome of PSC patients with UC resembled that of PSC without IBD.
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Affiliation(s)
- J Fevery
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - W Van Steenbergen
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - J Van Pelt
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - W Laleman
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - I Hoffman
- Paediatric Gastroenterology, Department of Clinical and Experimental Medicine, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - K Geboes
- Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - S Vermeire
- Gastroenterology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - F Nevens
- Hepatology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
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Althumairi AA, Lazarev MG, Gearhart SL. Inflammatory bowel disease associated neoplasia: A surgeon’s perspective. World J Gastroenterol 2016; 22:961-973. [PMID: 26811640 PMCID: PMC4716048 DOI: 10.3748/wjg.v22.i3.961] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is associated with increased risk of colorectal cancer (CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and inter-observer variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients’ morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes.
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19
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Abstract
BACKGROUND AND AIMS The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing disorders of unknown aetiology. The aim of this review is to present the latest epidemiology data on occurrence, disease course, risk for surgery, as well as mortality and cancer risks. MATERIAL AND METHODS Gold standard epidemiology data on the disease course and prognosis of patients with inflammatory bowel disease (IBD) are based on unselected population-based cohort studies. RESULTS The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has increased overall in Europe from 6.0 per 100,000 person-years in UC and 1.0 per 100,000 person-years in CD in 1962 to 9.8 per 100,000 person-years and 6.3 per 100,000 person-years in 2010, respectively. The highest incidence of IBD is found on the Faroe Islands. Overall, surgery rates have been declining over the last decades, partly due to aggressive medical therapy. Among IBD patients, mortality risk is increased by up to 50% in CD when compared to the background population, but this is not the case for UC. In CD, 25 - 50% deaths are disease-specific deaths, e.g. malnutrition, postoperative complications and intestinal cancer. In UC, disease-specific causes of deaths include colorectal cancer (CRC), and surgical and postoperative complications. The risk of CRC and small bowel cancer is increased two- to eightfold among IBD patients. Various subgroups carry increased risk of malignancy, e.g. those with persistent inflammation, long-standing disease, extensive disease, young age at diagnosis, family history of CRC and co-existing primary sclerosing cholangitis. The risk of extra-intestinal cancers, including lymphoproliferative disorders (LD) and intra- and extrahepatic cholangio carcinoma, is significantly higher among IBD patients. CONCLUSION In recent years, self-management and patient empowerment, combined with evolving eHealth solutions, has utilized epidemiological knowledge on disease patterns and has been improving compliance and the timing of adjusting therapies, thus optimizing efficacy by individualizing medication in the community setting.
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Affiliation(s)
- Johan Burisch
- Gastrounit, Medical Section, Hvidovre University Hospital , Hvidovre , Denmark
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20
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Choi WT, Rabinovitch PS, Wang D, Westerhoff M. Outcome of "indefinite for dysplasia" in inflammatory bowel disease: correlation with DNA flow cytometry and other risk factors of colorectal cancer. Hum Pathol 2015; 46:939-47. [PMID: 25962315 DOI: 10.1016/j.humpath.2015.03.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 03/17/2015] [Accepted: 03/18/2015] [Indexed: 01/04/2023]
Abstract
Dysplasia that develops in the setting of inflammatory bowel disease precedes colorectal cancer (CRC). The category of "indefinite for dysplasia (IND)" is used often in equivocal cases, but its clinical significance remains unclear. Flow cytometric analysis of DNA content (aneuploidy) has shown some promise in stratifying patients into low or high risk of CRC, but there are few reports that have specifically evaluated the outcome of IND. As such, we analyzed a series of 84 IND inflammatory bowel disease patients seen at the University of Washington and Harborview Medical Centers from 2003 to 2013 to determine the outcome of IND. Hospital electronic medical records were further reviewed to correlate outcome with the type of lesion (flat versus polypoid), primary sclerosing cholangitis, active inflammation in the area of IND, and DNA flow cytometric data. The data show that 13% of IND cases were found to have low-grade dysplasia, whereas only 2% of IND cases showed advanced neoplasia (high-grade dysplasia or CRC) after a mean follow-up of 28 months. The risk of neoplasia was not significantly associated with the type of lesion (P = .94 from log-rank test), primary sclerosing cholangitis (P = .94), or active inflammation (P = .41) in this cohort. However, the finding of DNA aneuploidy at baseline IND was predictive of subsequent detection of neoplasia (P = .037). IND patients with abnormal DNA flow cytometric results may warrant more careful follow-up, but conversely, IND in the setting of normal DNA content may require less frequent surveillance colonoscopy.
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Affiliation(s)
- Won-Tak Choi
- Department of Pathology, Rodger C. Haggitt Gastrointestinal and Hepatic Pathology Service, University of Washington School of Medicine, Seattle, WA 98195
| | - Peter S Rabinovitch
- Department of Pathology, Rodger C. Haggitt Gastrointestinal and Hepatic Pathology Service, University of Washington School of Medicine, Seattle, WA 98195
| | - Dongliang Wang
- Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY 13210
| | - Maria Westerhoff
- Department of Pathology, Rodger C. Haggitt Gastrointestinal and Hepatic Pathology Service, University of Washington School of Medicine, Seattle, WA 98195.
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KAMIYA TORU. Suitability of surveillance colonoscopy for patients with ulcerative colitis to detect colorectal cancer: current guidelines miss some early-stage cases. NAGOYA JOURNAL OF MEDICAL SCIENCE 2015; 77:237-44. [PMID: 25797989 PMCID: PMC4361526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 01/14/2015] [Indexed: 11/25/2022]
Abstract
Surveillance colonoscopy (SC) is considered important for the early detection and treatment of colorectal cancer (CRC) in patients with ulcerative colitis (UC). Here, we investigated whether current guidelines are appropriate in preventing UC patients from being diagnosed with CRC at an incurable stage. Among 1583 patients under treatment for UC, 27 patients were diagnosed with CRC. Of these, we excluded two patients who had not undergone colonoscopy before CRC diagnosis. We then divided the remaining patients into three groups based on colonoscopy interval (A, 1 year or less; B, between 1 and 2 years; and C, 2 years or longer). Fifteen patients had tubular adenocarcinomas, and 10 had other types (8 poorly differentiated adenocarcinomas, 1 mucinous adenocarcinoma, 1 endocrine cell carcinoma). Five (20%) of 25 patients developed CRC within 8 years after the onset of UC, of which one case was detected at stage IV. Six patients were classified into group A, 8 into group B, and 11 into group C. On distribution by histologic type, tubular adenocarcinomas were detected in stages 0 - II in 100% in group A, 100% in group B, and 57.1% in group C. In contrast, other types of carcinomas were detected in stage 0 - II in 100% in group A, 40% in group B, and 0% in group C. Current guideline recommendations for SC are not sufficient for the detection of early stage CRC in patients with UC. SC should be commenced earlier than recommended in the current guidelines and repeated annually.
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Affiliation(s)
- TORU KAMIYA
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Khosravi Khorashad A, Khajedaluee M, Mokhtari Amirmajdi E, Bahari A, Farzanehfar MR, Ahadi M, Abedini S, Abdollahi MR, Vakili R, Vossoughi Nia H. Frequency and risk factors of primary sclerosing cholangitis among patients with inflammatory bowel disease in North-East of Iran. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2015; 8:200-6. [PMID: 26328042 PMCID: PMC4553160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 02/19/2015] [Indexed: 11/11/2022]
Abstract
AIM To identify primary sclerosing cholangitis (PSC) predisposing factors in order to prevent inflammatory bowel disease (IBD) progression to PSC. BACKGROUND IBD is commonly associated with PSC and there is no effective therapy for PSC except for liver transplantation. PATIENTS AND METHODS This retrospective study was conducted on 447 IBD patients from IBD Clinics of Ghaem and Emam Reza Hospitals. Data were collected by interview and through a review of the patients' medical records. Patients were divided into two groups: those with IBD and PSC (IBD-PSC) and those without PSC. Variables were compared between two groups and those with statistically significant differences in IBD-PSC group were considered as predictive factors for the development of PSC. RESULTS The frequency of PSC in IBDs was 4.3% and all were ulcerative colitis. The mean age of patients with PSC was 39.1±11.33 years. The male to female proportion in PSCs was 3.8:1 and in IBDs was 0.9:1. There were statistically significant associations between PSC and gender, IBD duration and UC extension, mucocutaneous involvement, oral contraceptive pills (OCP) consumption, history of surgery and history of PSC in the first- degree relatives. CONCLUSION PSC frequency among IBD patients in North-East of Iran was 4.3%. It is recommended to limit OCP consumption in IBD patients. Identification and modification of probable predisposing risk factors, as well as early diagnosis of PSC are necessary.
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Affiliation(s)
- Ahmad Khosravi Khorashad
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Ghaem Hospital, Mashhad, Iran
| | - Mohammad Khajedaluee
- Department of Social Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Mokhtari Amirmajdi
- Gastroenterology and Hepatoloy Department, Nayshabour Faculty of Medical Sciences, Nayshabour, Iran
| | - Ali Bahari
- Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, MashhadUniversity of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Farzanehfar
- Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, MashhadUniversity of Medical Sciences, Mashhad, Iran
| | - Mitra Ahadi
- Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, MashhadUniversity of Medical Sciences, Mashhad, Iran
| | - Siavash Abedini
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Ghaem Hospital, Mashhad, Iran
| | - Mohammad Reza Abdollahi
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Ghaem Hospital, Mashhad, Iran
| | - Rosita Vakili
- Center of Pathological and Medical Diagnostic Services, Iranian Academic Center for Education, Culture & Research (ACECR), Mashhad Branch, Mashhad, Iran
| | - Hassan Vossoughi Nia
- Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, MashhadUniversity of Medical Sciences, Mashhad, Iran
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van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations (Spanish version)]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2015; 80:74-106. [PMID: 25769216 DOI: 10.1016/j.rgmx.2014.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 12/12/2022]
Affiliation(s)
- G van Assche
- En nombre de la ECCO; G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | - A Dignass
- G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
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Abstract
Patients with inflammatory bowel diseases (IBDs) are at increased risk of colorectal cancer (CRC), but the risk varies between different studies and seems to be decreasing. The cumulative risk of CRC has been reported to be 1%, 2%, and 5% after 10, 20, and over 20 years of disease duration, respectively, in recent meta-analysis. Disease duration and grade of inflammation are the main driving forces of dysplasia and CRC development. Also, the risk of extraintestinal cancers is increased in IBD, where the degree of immunosuppression and its duration are the most important risk factors. Most important extraintestinal malignancies are lymphomas and non-melanoma skin cancers, both of which are increased in patients receiving thiopurines. Also, extraintestinal manifestations or concomitant diseases such as primary sclerosing cholangitis predispose IBD patients to malignancies such as cholangiocarcinoma. History of previous cancer increases the risk of developing either new or recurrent cancers and should be taken into account when choosing therapy and planning surveillance. Dysplasia and cancer screening and surveillance must be individualized according to patients' risk factors. Malignancies are the second most common cause of death after cardiovascular diseases in both genders in patients with IBD.
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Affiliation(s)
- Urpo Nieminen
- Helsinki University Hospital, Department of Medicine, Division of Gastroenterology , Helsinki , Finland
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Nieminen U, Jussila A, Nordling S, Mustonen H, Färkkilä MA. Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case-control observational study based on registry data. Int J Cancer 2013; 134:189-96. [PMID: 23797639 DOI: 10.1002/ijc.28346] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Revised: 05/21/2013] [Accepted: 06/13/2013] [Indexed: 12/13/2022]
Abstract
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk for colorectal carcinoma (CRC). Earlier studies suggest that the severity of inflammation is an independent risk factor for CRC in ulcerative colitis (UC). We investigated the role of histological inflammation as a risk factor for colorectal dysplasia or CRC to better target dysplasia surveillance in IBD. By combining our hospital patient registry and pathology database between 1996 and 2008, we identified 183 IBD patients with dysplasia or CRC. The control group was collected from our registry of IBD patients. Histological severe inflammation was present in 41.4% of patients with dysplasia and in 24.1% of patients with CRC, but in only 4.3% of controls. Severe inflammation had an odds ratio (OR) of 31.8 [95% confidence interval (CI): 15.6-64.9] for dysplasia or carcinoma compared to patients with no inflammation. Among patients with mild to moderate inflammation, the OR was 2.6 (95% CI: 1.6-4.1). Disease duration increased the annual risk for dysplasia or CRC by 4.5%. Coexisting primary sclerosing cholangitis (PSC) did not elevate the risk, whereas use of thiopurines (OR = 0.09, 95% CI: 0.02-0.33) and also 5-aminosalicylic acid (OR 0.17, 95% CI: 0.017-1.01) protected against CRC. As conclusion, degree of inflammation and duration of disease cumulatively increase the risk for dysplasia and CRC. PSC was not identified as a risk factor. We demonstrated that use of thiopurines strongly protects against CRC. These results can be applied to better target dysplasia surveillance in IBD patients.
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Affiliation(s)
- Urpo Nieminen
- Clinic of Gastroenterology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
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26
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Kavanagh DO, Carter MC, Keegan D, Doherty G, Smith MJ, Hyland JMP, Mulcahy H, Sheahan K, O' Connell PR, O' Donoghue DP, Winter DC. Management of colorectal cancer in patients with inflammatory bowel disease. Tech Coloproctol 2013; 18:23-8. [PMID: 23407916 DOI: 10.1007/s10151-013-0981-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Accepted: 01/21/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC). METHODS A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed. RESULTS A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups. CONCLUSIONS Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.
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Affiliation(s)
- D O Kavanagh
- Center for Colorectal Disease, St. Vincent's University Hospital, Dublin, Ireland,
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27
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Chang WCL, Zenser TV, Cooper HS, Clapper ML. Differential response of flat and polypoid colitis-associated colorectal neoplasias to chemopreventive agents and heterocyclic amines. Cancer Lett 2013; 334:62-8. [PMID: 23415736 DOI: 10.1016/j.canlet.2013.02.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Revised: 02/06/2013] [Accepted: 02/06/2013] [Indexed: 02/09/2023]
Abstract
Individuals with ulcerative colitis face an increased risk of developing colorectal cancer and would benefit from early chemopreventive intervention. Results from preclinical studies in the mouse model of dextran sulfate sodium-induced colitis demonstrate that flat and polypoid colitis-associated dysplasias arise via distinct genetic pathways, impacted by the allelic status of p53. Furthermore, flat and polypoid dysplasias vary in their response to induction by the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and inhibition by 5-aminosalicylic acid, a common therapy for the maintenance of colitis patients. These data suggest that use of combination therapy is essential for the optimal inhibition of colitis-associated colorectal cancer.
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Affiliation(s)
- Wen-Chi L Chang
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States
| | - Terry V Zenser
- Department of Internal Medicine, St. Louis University, St. Louis, MO 63103, United States
| | - Harry S Cooper
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States; Department of Pathology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States
| | - Margie L Clapper
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, United States.
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28
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Van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013; 7:1-33. [PMID: 23040453 DOI: 10.1016/j.crohns.2012.09.005] [Citation(s) in RCA: 334] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 09/03/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Gert Van Assche
- Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network,University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
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29
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Imam MH, Thackeray EW, Lindor KD. Colonic neoplasia in young patients with inflammatory bowel disease and primary sclerosing cholangitis. Colorectal Dis 2013; 15:198-203. [PMID: 22712545 DOI: 10.1111/j.1463-1318.2012.03133.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM Current guidelines recommend annual surveillance for colorectal cancer (CRC) in all patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). The aim of our study was to validate the need for annual surveillance for colon neoplasia in patients ≤45 of age with a combined diagnosis of PSC and IBD. METHOD We identified patients, ≤45 years of age with a combined diagnosis of PSC and IBD, who were seen at the Mayo Clinic between 1995 and 2010. We then reviewed the medical records of the patients who developed colonic neoplasia defined as cancer, high-grade dysplasia (HGD) or dysplasia-associated lesion or mass (DALM). RESULTS In the population of 784 patients ≤45 years of age with a combined diagnosis of PSC and IBD, 10 (1.3%) of 784 developed colonic neoplasia during the follow-up period. Seven patients had colon cancer, one had HGD and two had a DALM. CONCLUSION Colonic neoplasia is uncommon in young patients (≤45 years of age) with a combined diagnosis of PSC and IBD. We suggest delaying surveillance in young patients and propose that studies should be carried out to clarify the cost-effectiveness of annual or biannual surveillance colonoscopies according to patient age.
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Affiliation(s)
- M H Imam
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
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30
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Tahara T, Arisawa T. Potential usefulness of DNA methylation as a risk marker for digestive cancer associated with inflammation. Expert Rev Mol Diagn 2012; 12:489-97. [PMID: 22702365 DOI: 10.1586/erm.12.38] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
DNA methylation has been deeply involved in the development and progression of digestive cancer, while aberrant DNA methylation has also often been observed in aged and inflammatory digestive tissues. Helicobacter pylori-related chronic gastritis, ulcerative colitis, and hepatitis B virus- and hepatitis C virus-related chronic hepatitis, are significant risk factors for developing cancer. A number of studies have revealed the specific methylation patterns for specific tissue types. DNA methylation status is stably transmitted to daughter cells. Also, unlike genetic mutations, it is possible to detect very tiny amounts of methylated DNA among tissues. Therefore, the use of aberrant methylation as a marker could be applicable to risk estimation of cancer development. We discuss the potential usefulness of DNA methylation as a risk marker for inflammation-associated digestive cancer, especially with attempts on gastric cancer, ulcerative colitis-associated cancer, and hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma.
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Affiliation(s)
- Tomomitsu Tahara
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, 1-98 Dengakugakubo Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
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31
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Bennis M, Tiret E. Chirurgische Behandlung der Colitis ulcerosa. COLOPROCTOLOGY 2012. [DOI: 10.1007/s00053-012-0275-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Krones E, Graziadei I, Trauner M, Fickert P. Evolving concepts in primary sclerosing cholangitis. Liver Int 2012; 32:352-69. [PMID: 22097926 DOI: 10.1111/j.1478-3231.2011.02607.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Accepted: 06/27/2011] [Indexed: 02/13/2023]
Abstract
Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC.
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Affiliation(s)
- Elisabeth Krones
- Department of Internal Medicine, Medical University of Graz, Graz, Austria
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Surgical management of ulcerative colitis. Langenbecks Arch Surg 2011; 397:11-7. [PMID: 21922296 DOI: 10.1007/s00423-011-0848-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Accepted: 09/06/2011] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Surgery is the only curative option in the treatment of ulcerative colitis. Despite advances in the medical management surgery is required in about a third of patients. SURGICAL MANAGEMENT In the acute setting surgery is indicated when medical treatment fails to improve an episode of acute severe colitis. The intervention of choice is a staged colectomy with end ileostomy and preservation of the rectal stump in the first instance. Indications for elective surgery are failure of medical therapy and malignant transformation. The surgical options include conventional proctectomy with ileostomy or a Kock's continent ileostomy and colectomy with an ileorectal anastomosis. The current gold standard is restorative proctocolectomy with ileal pouch-anal anastomosis. Most frequently the technique includes a J pouch with a stapled anastomosis and temporary faecal diversion with a loop ileostomy. Laparoscopic pouch surgery is a feasible and safe option with an excellent cosmetic result. CONCLUSIONS Although the morbidity remains significant after surgery, the quality of life is good with a satisfactory long-term functional outcome.
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Basseri RJ, Basseri B, Papadakis KA, Zeef LAH, Hayes A, Salmo E, Haboubi N, Iovanna JL, Carlson GL, Warhurst G. Dysplasia and cancer in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2011; 5:59-66. [PMID: 21309672 DOI: 10.1586/egh.10.77] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease associated with an increased risk of colorectal cancer (CRC). Although CRC occurs in a minority of IBD patients (1%), it carries a high mortality and accounts for 20% of IBD-related mortality. Established risk factors for the development of CRC in IBD include disease duration of 8 years or more, family history of CRC, extensive colitis and primary sclerosing cholangitis. Meticulous colonoscopy and anti-inflammatory medications can reduce the risk of developing CRC. The future of IBD surveillance involves the use of novel endoscopic techniques (chromoendoscopy, narrow-band imaging, confocal laser endomicroscopy and autofluorescence) to enhance colonoscopic accuracy, in concert with chemopreventative medications to help reduce the risk of CRC in IBD.
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Affiliation(s)
- Robert J Basseri
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Tahara T, Shibata T, Nakamura M, Okubo M, Yamashita H, Yoshioka D, Yonemura J, Hirata I, Arisawa T. Association between polymorphisms in the XRCC1 and GST genes, and CpG island methylation status in colonic mucosa in ulcerative colitis. Virchows Arch 2011; 458:205-11. [PMID: 21234761 DOI: 10.1007/s00428-010-1038-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2010] [Revised: 12/22/2010] [Accepted: 12/29/2010] [Indexed: 02/01/2023]
Abstract
CpG island hypermethylation (CIHM) is frequently observed in the colonic mucosa in ulcerative colitis (UC) and is deeply involved in UC-associated colorectal carcinogenesis. We evaluated the influence of common polymorphisms related to DNA repair or xenobiotic pathway (XRCC1, GSTP1, GSTT1, and GSTM1) on the individual susceptibility to CIHM status in the non-neoplastic rectal mucosa in UC patients. XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 84 UC patients without neoplastic lesions, in relation to CIHM in the rectal mucosa of three candidate CpG loci (p14, p16, and CDH1) assessed by methylation-specific polymerase chain reaction. XRCC1 codon 399 Arg/Gln genotype (odds ratio (OR) = 0.31, 95%CI = 0.12-0.81, p = 0.017) and 399 Gln carrier (GlnGln+Arg/Gln: OR = 0.30, 95%CI = 0.12-0.76, p = 0.01) were significantly associated with reduced susceptibility to CIHM of the CDH1 promoter. GSTP1 Val carrier (Ile Val+Val/Val) also held a significantly lower susceptibility to CIHM of the p16 promoter (OR = 0.26, 95%CI = 0.08-0.86, p = 0.028). In contrast, GSTT1 present genotype (OR = 3.16, 95%CI = 1.27-7.89, p = 0.01) was significantly associated with increased susceptibility to CIHM of the same gene. XRCC1 codon 399 Gln/Gln genotype was significantly associated with lower mean number of CIHM when compared to the Arg/Arg genotype (1.53 ± 1.01 vs. 0.63 ± 1.06, p = 0.024). In addition, the GSTP1 Ile/Val carrier (Ile/Val+Val/Val) was also significantly associated with lower mean number of CIHM (1.43 ± 1.03 vs. 0.84 ± 1.07, p = 0.03). XRCC1 Arg399Gln and GSTP1 Ile104Val polymorphisms may influence the CIHM status in the rectal mucosa of UC patients and may be substantially involved in UC-associated carcinogenesis.
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Affiliation(s)
- Tomomitsu Tahara
- Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
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Viennot S, Deleporte A, Moussata D, Nancey S, Flourié B, Reimund JM. Colon cancer in inflammatory bowel disease: recent trends, questions and answers. ACTA ACUST UNITED AC 2010; 33 Suppl 3:S190-201. [PMID: 20117342 DOI: 10.1016/s0399-8320(09)73154-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with chronic colitis (ulcerative colitis or colonic Crohn's disease) have an increased risk of colorectal cancer (CRC). Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients. This may also be one of the reasons explaining the role of 5-aminosalicylates as chemopreventive agents for CRC in inflammatory bowel disease (IBD) patients with colonic involvement. Beside chemoprevention, colonoscopic screening and surveillance have been shown to be the cornerstone for CRC prevention and early detection in this particular patients' population. Periodic surveillance colonoscopy to detect dysplasia has been shown to decrease the mortality attributed to CRC. More recently, progress in imaging techniques increased our ability to identify dysplasia, and should probably now be considered to be an integral part of surveillance colonoscopy. In the future, further improvement of our knowledge of CRC biology, refinement of imaging techniques, as well as molecular discovery (e.g. identification of specific mutations in stool DNA extracts), might lead to develop more accurate diagnostic strategies to reduce the morbidity and mortality related to CRC in patients with ulcerative colitis or colonic Crohn's disease.
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Affiliation(s)
- S Viennot
- Centre Hospitalier Universitaire de Caen, Service d'Hépato-Gastroentérologie et Nutrition, Pôle Reins-Digestif-Nutrition, Hôpital Côte de Nacre, B.P. 95182, 14033 Caen cedex 9, France
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Kiran RP, Khoury W, Church JM, Lavery IC, Fazio VW, Remzi FH. Colorectal cancer complicating inflammatory bowel disease: similarities and differences between Crohn's and ulcerative colitis based on three decades of experience. Ann Surg 2010; 252:330-5. [PMID: 20622662 DOI: 10.1097/sla.0b013e3181e61e69] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION The aim of this study was to evaluate patient- and tumor-related characteristics for patients undergoing surgery for cancer complicating inflammatory bowel disease (IBD), and to assess differences between patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS Data on all IBD patients with colon and rectal cancer (CRC) undergoing surgery between 1980 and 2007 were evaluated from prospectively maintained CRC and IBD databases. Clinical presentation, tumor stage, presence of associated dysplasia, and short- and long-term outcomes after surgery were investigated. Outcomes for IBD patients were compared with a matched group of patients with sporadic cancer. RESULTS A total of 240 IBD patients (64 CD and 176 UC) with CRC were identified. At the time of CRC diagnosis, 68% UC and 26% CD patients had pancolitis. About 92% of the patients who underwent preoperative colonoscopy were noted to have suspicious lesions. Although 92.5% of the patients had a preoperative histopathologic diagnosis of cancer or dysplasia, incidental diagnosis of cancer in the resection specimen was made in 3%. Examination of the resection specimen revealed synchronous dysplasia in 48% of the patients and synchronous cancer in 12% patients. Tumor location was rectum in 36%, right colon in 28%, sigmoid colon in 17%, transverse colon 10%, and left colon in 9% of patients. CD patients were diagnosed at a more advanced cancer stage than UC. Local recurrence and overall 5-year survival rates were comparable (5.6% vs. 6.7%, P = 0.78 and 77% vs. 72%, P = 0.5, respectively) for patients with IBD and sporadic cancer. CONCLUSIONS Most IBD cancer can be diagnosed or suspected on the basis of endoscopic findings, biopsy of areas of active colitis, and an incidental finding of malignancy after colorectal resection for other indications is rare. CD patients present with a more advanced cancer stage. Optimal endoscopic surveillance may identify most patients with IBD cancer.
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Affiliation(s)
- Ravi P Kiran
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA.
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Abstract
Patients with ulcerative colitis (UC) are at an increased risk for the development of colorectal cancer (CRC). Unlike sporadic CRC, the cancer in UC patients arises from a focal or multifocal dysplastic mucosa in areas of inflammation. The clinical features of UC-associated cancer are similar to those found in patients with hereditary non-polyposis colorectal cancer. As with other varieties of CRC, UC-associated cancer exhibits a variety of genetic and molecular changes/abnormalities. These abnormalities are however clustered in areas of mucosae with histological abnormalities. The magnitude and timing of these changes are however significantly different. Surveillance and identification of patients at risk for cancer are a challenging problem.
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Affiliation(s)
- Mahmoud N Kulaylat
- Department of Surgery, State University of New York-Buffalo, Kaleida Health, Buffalo General Hospital, Buffalo, New York 14203, USA.
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Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is being diagnosed with increasing frequency. The most feared complication is the presence or development of cholangiocarcinoma (CCA). The present review summarizes recent data with regards to diagnosis, pathobiology and treatment. RECENT FINDINGS Several investigations have focused on aspects of the molecular biology of CCA in general; such data should be explored now in the context of PSC-related CCA to yield new diagnostic markers and approaches for therapy. SUMMARY CCA has to be suspected in any new PSC patient presenting with jaundice. Exploration should include carbohydrate antigen19-9 and two imaging techniques. Endoscopic cholangioscopy might become very rewarding. Important progress has been achieved in liver transplantation by the use of preoperative radio-chemotherapy. Molecular biology points to inflammation-induced cytokines with mutagenic action and to the relevance of extracellular matrix proteins for invasion but also for proliferation. Micro-RNAs prove to be very important in the control of cell proliferation, differentiation and apoptosis. Mutated p53, cyclins, wnt/beta-catenin signaling, proliferation indices, mucins, carbohydrate antigen19-9, CRP and aneuploidy appear to hold significant potential as predictors of outcome in CCA. It is expected that the further unraveling of these molecular processes will ultimately lead to development of tests allowing early diagnosis and to development of medical approaches to retard tumor formation or recurrence following surgical interventions.
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Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010; 51:660-78. [PMID: 20101749 DOI: 10.1002/hep.23294] [Citation(s) in RCA: 833] [Impact Index Per Article: 55.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Campbell F, Maxwell R. Rationale for cancer prevention strategies in high-risk ulcerative colitis. Surgeon 2009; 7:96-100. [DOI: 10.1016/s1479-666x(09)80024-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Hancock L, Mortensen NJ. How often do IBD patients require resection of their intestine? Inflamm Bowel Dis 2008; 14 Suppl 2:S68-9. [PMID: 18816762 DOI: 10.1002/ibd.20600] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- L Hancock
- Department of Colorectal Surgery, John Radcliff Hospital, Oxford, UK
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Abstract
Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in cirrhosis and need for liver transplantation and reduced life expectancy. The majority of cases occur in young and middle-aged men, often in association with inflammatory bowel disease. The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature. No effective medical therapy has been identified. The multiple complications of primary sclerosing cholangitis include metabolic bone disease, dominant strictures, bacterial cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of primary sclerosing cholangitis. Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease, although recurrence in the allografted liver has been described. A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass, prominence of plasma cells within the lesions, and steroid responsiveness.
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Abstract
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins. To reduce CRC mortality in IBD, colonoscopic surveillance with random biopsies remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Patients with small intestinal Crohn's disease are at increased risk of small bowel adenocarcinoma. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. Other extra intestinal cancers, such as hepatobiliary and hematopoietic cancer, have shown variable incidence rates. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.
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Affiliation(s)
- Jianlin Xie
- GI Division, Mount Sinai School of Medicine, One Gustave Levy Place, New York City, NY 10029, USA
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Abstract
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins. To reduce CRC mortality in IBD, colonoscopic surveillance with random biopsies remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Patients with small intestinal Crohn’s disease are at increased risk of small bowel adenocarcinoma. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. Other extra intestinal cancers, such as hepatobiliary and hematopoietic cancer, have shown variable incidence rates. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.
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Inflammatory bowel disease: the problems of dysplasia and surveillance. Tech Coloproctol 2007; 11:299-309. [DOI: 10.1007/s10151-007-0386-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2006] [Accepted: 02/04/2007] [Indexed: 01/07/2023]
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Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig Dis Sci 2007; 52:3123-35. [PMID: 17431781 DOI: 10.1007/s10620-006-9681-4] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2005] [Accepted: 11/08/2006] [Indexed: 02/06/2023]
Abstract
Primary sclerosing cholangitis (PSC) can lead to the development of cholangiocarcinoma (CCA). The tumor may present as an intrahepatic focal cholangiocellular carcinoma but more often as a ductal infiltrating desmoplastic lesion. CCA is found synchronously with the diagnosis of PSC in 20-30% and within 1 year in 50%. During later follow-up, the yearly developmental rate of CCA is 0.5-1.5%. Most patients with PSC and CCA do not yet have cirrhosis but present with a severe stenosis at the hilum of the liver. This type of tumor is difficult to diagnose by imaging techniques.(18)F-FDG-PET scanning and CEA or CA 19-9 are not early diagnostic tools. Regular MRI, multislice CT, and repeated endoscopically obtained brush cytology of stenotic lesions are recommended. The recent use of more extensive surgical resection techniques in patients with CCA results in 5-year survival rates of > or =50%. If tumors are small or incidental findings, liver transplantation leads to a 3- to 5-year survival rate of 35%. Pretransplant radiotherapy with 5-FU chemosensitization followed by endoscopic brachytherapy with iridium-192 seems to greatly improve the outcome of transplantation. Treatment with ursodeoxycholic acid may prevent development of CCA.
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Affiliation(s)
- Johan Fevery
- Division of Hepatobiliary, University Hospital Gasthuisberg, Catholic University of Leuven, B3000 Leuven, Belgium.
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Konishi K, Shen L, Wang S, Meltzer SJ, Harpaz N, Issa JPJ. Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias. Gastroenterology 2007; 132:1254-60. [PMID: 17408633 DOI: 10.1053/j.gastro.2007.01.035] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2006] [Accepted: 12/14/2006] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS We previously reported that a high degree of age-related methylation was found in both the dysplastic and nondysplastic mucosa of patients with ulcerative colitis (UC). Whether this translates into hypermethylation in UC-associated cancers (UC-Cs) is not known. METHODS We evaluated the methylation status of 11 genes (MINT1, 2, 31, hMLH1, p16, p14, MGMT, HPP1, SFRP1, ERalpha, and LINE-1) in 48 UC-Cs, 21 UC-associated dysplasias, and 69 sporadic colorectal cancers (S-CRCs) using a quantitative bisulfite pyrosequencing analysis. RESULTS Methylation levels in UC-Cs were lower than S-CRCs for all the genes except MGMT. A methylation index based on the average of Z-scores, for type C (cancer-specific genes: MINT1, MINT2, MINT31, hMLH1, p16, and p14) was -.97 in UC-Cs and .92 in S-CRCs (P = .009). That of type A (age-related genes: HPP1, SFRP1, and ERalpha) was -1.97 in UC-Cs and 1.24 in S-CRCs (P < .001). We observed a significant difference in the incidence of CpG island methylator phenotype between UC-Cs and S-CRCs (8 of 48 [17%] and 26 of 69 [38%]; P = .022). UC-associated dysplasias had significantly higher methylation of type A gene than UC-Cs (Z-score: .07 and -1.97, respectively; P < .001). By contrast, global DNA methylation measured using a LINE-1 assay was significantly higher in UC-Cs than in S-CRCs (58.2% vs 51.0%, P < .001). CONCLUSIONS DNA methylation alterations are uncommon in UC cancers. Given that both genetic and epigenetic changes are common in UC mucosa and dysplasias, we speculate that the genetic changes lead to a more aggressive clinical course than epigenetic changes.
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Affiliation(s)
- Kazuo Konishi
- Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Delaunoit T, Limburg PJ, Goldberg RM, Lymp JF, Loftus EV. Colorectal cancer prognosis among patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2006; 4:335-42. [PMID: 16527697 DOI: 10.1016/j.cgh.2005.12.035] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Inflammatory bowel disease (IBD) is associated with an increased risk for colorectal cancer (CRC). However, the genetic, endoscopic, and histologic features of IBD-associated CRC differ from cancers that arise sporadically. The objectives of this study were to describe the clinicopathologic features of IBD-associated CRC and to compare survival rates between patients with IBD-associated CRC and patients with sporadic CRC. METHODS There were 290 patients with IBD-associated CRC (241 with chronic ulcerative colitis [CUC] and 49 with Crohn's disease) and an equal number of age- and sex-matched sporadic CRC patients who were evaluated at the Mayo Clinic between 1976 and 1996. Medical records were reviewed retrospectively for demographic features, endoscopic and histologic characteristics, and vital status at the time of the last follow-up evaluation. The actuarial survival of each group was calculated by the Kaplan-Meier method. The influence of clinical features on survival was assessed using Cox proportional hazards regression modeling. RESULTS The median age at diagnosis of IBD-related CRC was 48 years. Fifty-five percent of IBD-related tumors were distal to the splenic flexure compared with 78% of sporadic tumors. During a median follow-up period of 5 years, 163 IBD-associated CRC patients died (56%), compared with 164 sporadic CRC patients (57%). The 5-year survival rates were 54% in the IBD-CRC subgroup vs 53% in the sporadic CRC subgroup (P = .94, log-rank). CONCLUSIONS CUC-related CRC is diagnosed at a relatively young age, and IBD-related tumors tend to be distributed more evenly across the colorectum than sporadic tumors. The survival rates for IBD-associated and sporadic CRC were similar.
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Affiliation(s)
- Thierry Delaunoit
- Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
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