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Muller C, Yamada A, Ikegami S, Haider H, Komaki Y, Komaki F, Micic D, Sakuraba A. Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:622-630.e7. [PMID: 34089849 DOI: 10.1016/j.cgh.2021.05.057] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 05/28/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. METHODS Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. RESULTS Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. CONCLUSIONS Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.
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Affiliation(s)
- Charles Muller
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Akihiro Yamada
- Section of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Sachie Ikegami
- Department of Pathology, NorthShore University HealthSystem, Evanston, Illinois
| | - Haider Haider
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Yuga Komaki
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Fukiko Komaki
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Dejan Micic
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Atsushi Sakuraba
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois.
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Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre. Cancers (Basel) 2021; 13:cancers13051066. [PMID: 33802297 PMCID: PMC7959130 DOI: 10.3390/cancers13051066] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 12/30/2022] Open
Abstract
Simple Summary Serrated polyposis syndrome is characterized by the development of large and/or multiple serrated polyps throughout the colorectum and is associated with an increased risk of colorectal cancer (CRC). Even though CRC incidence is low under adequate endoscopic follow-up, a substantial risk of advanced neoplasia (AN) has been described. Nevertheless, very few studies have focused on long-term surveillance. The main aim of this study was to evaluate the incidence of AN in a single-centre cohort followed over 10 years. Within endoscopic surveillance we did not find any CRC and we observed that five-year cumulative incidences of AN were much lower than in other studies. However, a significant reduction of these incidences during follow-up was not proven. Individuals at higher risk of AN were those who fulfilled both 2010 WHO criteria I and III. Our results suggest that at least patients at lower risk might benefit from the extension of surveillance intervals. Abstract Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance.
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Rubio CA, Schmidt PT. Asymmetric crypt fission in sessile serrated lesions. J Clin Pathol 2020; 74:712-717. [PMID: 33046564 DOI: 10.1136/jclinpath-2020-207008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Sessile serrated lesions without dysplasia (SSL-ND) are epitomised by dilated crypts with epithelial serrations and architectural distortions portraying boot-shapes, L-shapes or inverted-T shapes. Recently, crypts in asymmetric fission were detected in SSL-ND. The purpose was to assess the frequency of crypts in asymmetric fission in a cohort of SSL-ND. METHODS The frequency of crypts in fission was assessed in 60 SSL-ND, the distribution of cell proliferation in 48 SSL-ND and the expression of maspin, a tumour-suppressor protein, in 29 SSL-ND. RESULTS Out of the 60 SSL-ND, 40 (66.7%) showed crypts in fission: 39 (65%) SSL-ND had crypts in asymmetric fission and one SSL-ND (1.7%), in symmetric fission (p<0.05). Of 1495 crypts recorded in the 60 SSL-ND, 73 (4.9%) were in asymmetric fission but only one (0.06%), in symmetric fission (p<0.05). Out of the 48 Ki67-immunostained SSL-ND,15 (31%) showed randomly distributed proliferating cell-domains. All 29 SSL-ND revealed maspin-upregulation (including crypts in asymmetric and symmetric fission). In contrast, the normal colon mucosa showed occasional single crypts in symmetric fission, proliferating cell-domains limited to the lower thirds of the crypts, absence of crypts in asymmetric fission and remained maspin negative. CONCLUSIONS SSL-ND thrive with crypts in asymmetric fission displaying randomly distributed proliferating cell-domains and maspin-upregulation. These histo-biological aberrations disclose pathological cryptogenesis and suggest possibly unfolding somatic mutations in SSL-ND. The present findings may open new vistas on the parameters pertinent to the susceptibility of SSL-ND to develop dysplasia and carcinoma.
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Affiliation(s)
- Carlos A Rubio
- Department of Pathology, Karolinska Institute, Stockholm, Sweden
| | - Peter T Schmidt
- Medicine (Solna), Karolinska Institute and Ersta Hospital, Stockholm, Sweden
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Bleijenberg AGC, IJspeert JEG, van Herwaarden YJ, Carballal S, Pellisé M, Jung G, Bisseling TM, Nagetaal ID, van Leerdam ME, van Lelyveld N, Bessa X, Rodríguez-Moranta F, Bastiaansen B, de Klaver W, Rivero L, Spaander MCW, Koornstra JJ, Bujanda L, Balaguer F, Dekker E. Personalised surveillance for serrated polyposis syndrome: results from a prospective 5-year international cohort study. Gut 2020; 69:112-121. [PMID: 30981990 PMCID: PMC6943249 DOI: 10.1136/gutjnl-2018-318134] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC). International guidelines recommend surveillance intervals of 1-2 years. However, yearly surveillance likely leads to overtreatment for many. We prospectively assessed a surveillance protocol aiming to safely reduce the burden of colonoscopies. METHODS Between 2013 and 2018, we enrolled SPS patients from nine Dutch and Spanish hospitals. Patients were surveilled using a protocol appointing either a 1-year or 2-year interval after each surveillance colonoscopy, based on polyp burden. Primary endpoint was the 5-year cumulative incidence of CRC and advanced neoplasia (AN) during surveillance. RESULTS We followed 271 SPS patients for a median of 3.6 years. During surveillance, two patients developed CRC (cumulative 5-year incidence 1.3%[95% CI 0% to 3.2%]). The 5-year AN incidence was 44% (95% CI 37% to 52%), and was lower for patients with SPS type III (26%) than for patients diagnosed with type I (53%) or type I and III (59%, p<0.001). Most patients were recommended a 2-year interval, and those recommended a 2-year interval were not at increased risk of AN: AN incidence after a 2-year recommendation was 15.6% compared with 24.4% after a 1-year recommendation (OR 0.57, p=0.08). CONCLUSION Risk stratification substantially reduced colonoscopy burden while achieving CRC incidence similar to previous studies. AN incidence is considerable in SPS patients, but extension of surveillance intervals was not associated with increased AN in those identified as low-risk by the protocol. We identified SPS type III patients as low-risk group that might benefit from even less frequent surveillance. TRIAL REGISTRATION NUMBER The study was registered on http://www.trialregister.nl; trial-ID NTR4609.
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Affiliation(s)
- Arne GC Bleijenberg
- Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joep EG IJspeert
- Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Yasmijn J van Herwaarden
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Sabela Carballal
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - María Pellisé
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Gerhard Jung
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Tanya M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Iris D Nagetaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Monique E van Leerdam
- Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Niels van Lelyveld
- Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, The Netherlands
| | - Xavier Bessa
- Gastroenterology, Institut Hospital del Mar d’Investigacions Mediques, Barcelona, Spain
| | | | - Barbara Bastiaansen
- Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Willemijn de Klaver
- Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Liseth Rivero
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Manon CW Spaander
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Jan Jacob Koornstra
- Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Luis Bujanda
- Gastroenterology, Donostia Hospital, San Sebastian, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Evelien Dekker
- Gastroenterology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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López-Vicente J, Rodríguez-Alcalde D, Hernández L, Riu Pons F, Vega P, Herrero Rivas JM, Santiago García J, Salces Franco I, Bustamante Balén M, López-Cerón M, Pellisé M. Panchromoendoscopy Increases Detection of Polyps in Patients With Serrated Polyposis Syndrome. Clin Gastroenterol Hepatol 2019; 17:2016-2023.e6. [PMID: 30366156 DOI: 10.1016/j.cgh.2018.10.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 10/02/2018] [Accepted: 10/08/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Serrated polyposis syndrome (SPS), characterized by multiple and/or large proximal serrated lesions, increases the risk of colorectal cancer. Serrated lesions often are missed during colonoscopy but panchromoendoscopy can increase their detection in an average-risk population. We performed a randomized controlled study to determine the efficacy of panchromoendoscopy in detection of polyps in patients with SPS. METHODS Patients with SPS (n = 86 patients) underwent tandem high-definition (HD) colonoscopies from February 2015 through July 2016 at 7 centers in Spain. Patients were assigned randomly to groups that received 2 HD white-light endoscopy examinations (HD-WLE group; n = 43) or HD-WLE followed by 0.4% indigo carmine panchromoendoscopy (HD-CE group; n = 43). For each procedure, polyps detected were described, removed, and analyzed by histology. The primary outcome was additional polyp detection rate, defined as the number of polyps detected during the second inspection divided by the total number of polyps detected during the first and the second examination. RESULTS A total of 774 polyps were detected (362 in the HD-WLE group and 412 in the HD-CE group); 54.2% were hyperplastic, 13.8% were adenomas, and 10.9% were sessile serrated polyps. There was a significantly higher additional polyp detection rate in the HD-CE group (0.39; 95% CI, 0.35-0.44) than in the HD-WLE group (0.22; 95% CI, 0.18-0.27) (P < .001). A higher additional rate of serrated lesions proximal to the sigmoid colon were detected in the second inspection with HD-CE (0.40; 95% CI, 0.33-0.47) than with HD-WLE (0.24; 95% CI, 0.19-0.31) (P = .001). Detection of adenomas and serrated lesions greater than 10 mm did not differ significantly between groups. In a multivariate logistic regression analysis, only use of HD-CE was associated independently with increased polyp detection throughout the colon. CONCLUSIONS In a randomized controlled trial, we found that panchromoendoscopy increases detection of polyps (mostly of small serrated lesions) and should be considered the standard of care in patients with SPS. Studies are needed to determine the effects of this strategy on the incidence of advanced neoplasia during long-term follow-up evaluation. ClinicalTrials.gov no: NCT03476434.
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Affiliation(s)
| | | | - Luis Hernández
- Gastroenterology Department, Hospital Santos Reyes de Aranda de Duero, Spain
| | - Fausto Riu Pons
- Gastroenterology Department, Hospital de Mar de Barcelona, Spain
| | - Pablo Vega
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Spain
| | | | - José Santiago García
- Gastroenterology Department, Hospital Universitario Puerta de Hierro de Madrid, Spain
| | | | | | - María López-Cerón
- Gastroenterology Department, Hospital Universitario 12 de Octubre de Madrid, Spain
| | - María Pellisé
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Spain.
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Bleijenberg AGC, IJspeert JEG, Carballal S, Pellise M, Jung G, van Herwaarden YJ, Bisseling TM, Nagtegaal ID, van Leerdam ME, Spaander MCW, van Lelyveld N, Bessa X, Rodríguez-Alcalde D, Bastiaansen BAJ, de Klaver W, Bemelman WA, Bujanda L, Koornstra JJ, Rivero L, Rodríguez-Moranta F, Balaguer F, Dekker E. Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study. Am J Gastroenterol 2019; 114:1512-1519. [PMID: 31403493 DOI: 10.14309/ajg.0000000000000339] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Serrated polyposis syndrome (SPS) is accompanied by a substantially increased colorectal cancer (CRC) risk. To prevent or treat CRC in patients with a very high polyp burden, (sub)total colectomy with ileorectal or ileosigmoidal anastomosis is regularly performed. The CRC risk after (sub)total colectomy might be decreased, but evidence is lacking. We aimed to assess the yield of endoscopic surveillance in patients with SPS who underwent (sub)total colectomy. METHODS For this post hoc analysis, we used prospectively collected data from a large international prospective cohort study. We included patients diagnosed with SPS (World Health Organization type I and/or III) who underwent (sub)total colectomy. Primary endpoint was the cumulative 5-year incidence of CRC and advanced neoplasia (AN). RESULTS Forty-eight patients (mean age 61 [±7.8]; 52% men) were included and followed up for a median of 4.7 years (interquartile range 4.7-5.1). None of the patients developed CRC during follow-up. Five patients developed AN, corresponding to a cumulative 5-year AN incidence of 13% (95% confidence interval 1.2-23). In 4 patients, AN was diagnosed at the first surveillance endoscopy after study inclusion, and in 1 patient, AN was detected during subsequent rounds of surveillance. The risk of AN was similar for patients with ileorectal and ileosigmoidal anastomosis (logrank P = 0.83). DISCUSSION (Sub)total colectomy mitigates much of the excess risk of CRC in patients with SPS. Advanced neoplasms are mainly detected at the first endoscopy after (sub)total colectomy. Based on these results, after the first surveillance, intervals might be extended beyond the currently recommended 1-2 years.
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Affiliation(s)
- A G C Bleijenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands
| | - J E G IJspeert
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands
| | - S Carballal
- Gastroenterology Department, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - M Pellise
- Gastroenterology Department, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - G Jung
- Gastroenterology Department, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Y J van Herwaarden
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - T M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - M E van Leerdam
- Department of Gastroenterology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - M C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - N van Lelyveld
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - X Bessa
- Gastroenterology Department, Hospital Del Mar, Barcelona, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Spain
| | - D Rodríguez-Alcalde
- Digestive Disease Section, Hospital Universitario de Móstoles, Móstoles, Spain
| | - B A J Bastiaansen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands
| | - W de Klaver
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands
| | - W A Bemelman
- Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands
| | - L Bujanda
- Gastroenterology Department, Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad Del País Vasco (UPV/EHU), San Sebastián, Spain
| | - J J Koornstra
- Department of Gastroenterology & Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - L Rivero
- Gastroenterology Department, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - F Rodríguez-Moranta
- Gastroenterology Department, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - F Balaguer
- Gastroenterology Department, Hospital Clínic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - E Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands
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Valle L, de Voer RM, Goldberg Y, Sjursen W, Försti A, Ruiz-Ponte C, Caldés T, Garré P, Olsen MF, Nordling M, Castellvi-Bel S, Hemminki K. Update on genetic predisposition to colorectal cancer and polyposis. Mol Aspects Med 2019; 69:10-26. [PMID: 30862463 DOI: 10.1016/j.mam.2019.03.001] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 02/26/2019] [Accepted: 03/05/2019] [Indexed: 02/06/2023]
Abstract
The present article summarizes recent developments in the characterization of genetic predisposition to colorectal cancer (CRC). The main themes covered include new hereditary CRC and polyposis syndromes, non-CRC hereditary cancer genes found mutated in CRC patients, strategies used to identify novel causal genes, and review of candidate genes that have been proposed to predispose to CRC and/or colonic polyposis. We provide an overview of newly described genes and syndromes associated with predisposition to CRC and polyposis, including: polymerase proofreading-associated polyposis, NTHL1-associated polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations as a rare cause of hereditary nonpolyposis CRC. The implementation of next generation sequencing approaches for genetic testing has exposed the presence of pathogenic germline variants in genes associated with hereditary cancer syndromes not traditionally linked to CRC, which may have an impact on genetic testing, counseling and surveillance. The identification of new hereditary CRC and polyposis genes has not deemed an easy endeavor, even though known CRC-related genes explain a small proportion of the estimated familial risk. Whole-genome sequencing may offer a technology for increasing this proportion, particularly if applied on pedigree data allowing linkage type of analysis. The final section critically surveys the large number of candidate genes that have been recently proposed for CRC predisposition.
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Affiliation(s)
- Laura Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, Hospitalet de Llobregat, Spain; Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
| | - Richarda M de Voer
- Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Yael Goldberg
- Raphael Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel
| | - Wenche Sjursen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medical Genetics, St Olavs University Hospital, Trondheim, Norway
| | - Asta Försti
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany
| | - Clara Ruiz-Ponte
- Fundación Pública Galega de Medicina Xenómica, Grupo de Medicina Xenómica, Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
| | - Trinidad Caldés
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain; Oncology Molecular Laboratory, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain
| | - Pilar Garré
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain; Oncology Molecular Laboratory, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain
| | - Maren F Olsen
- Department of Medical Genetics, St Olavs University Hospital, Trondheim, Norway
| | - Margareta Nordling
- Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sergi Castellvi-Bel
- Genetic Predisposition to Gastrointestinal Cancer Group, Gastrointestinal and Pancreatic Oncology Team, Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
| | - Kari Hemminki
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
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Cassese G, Amendola A, Maione F, Giglio MC, Pagano G, Milone M, Aprea G, Luglio G, De Palma GD. Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management. Gastroenterol Res Pract 2019; 2019:9179718. [PMID: 30774654 PMCID: PMC6350577 DOI: 10.1155/2019/9179718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023] Open
Abstract
Prompt diagnosis and correct management of the so called "serrated lesions" (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
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Affiliation(s)
- Gianluca Cassese
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Alfonso Amendola
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Francesco Maione
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Mariano Cesare Giglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gianluca Pagano
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Marco Milone
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Aprea
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gaetano Luglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Domenico De Palma
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
- Center of Excellence for Technological Innovation in Surgery, University of Naples “Federico II”, Italy
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9
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Abbass MA, Kalady MF. Serrated polyposis syndrome: Diagnosis and management. SEMINARS IN COLON AND RECTAL SURGERY 2018. [DOI: 10.1053/j.scrs.2018.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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10
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Zorcolo L, Fantola G, Balestrino L, Restivo A, Vivanet C, Spina F, Cabras F, Ambu R, Casula G. MUTYH-associated colon disease: Adenomatous polyposis is only one of the possible phenotypes. A family report and literature review. TUMORI JOURNAL 2018; 97:676-80. [DOI: 10.1177/030089161109700523] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Aims and background The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome. Patients and methods A family with a history of right-sided colon cancer and multiple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MUTYH and the role of prophylactic surgery. Results Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, developed four hyperplastic lesions, while the heterozygote brother had a large flat serrated adenoma of the right colon removed at the age of 50. Conclusion Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrated adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP.
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Affiliation(s)
- Luigi Zorcolo
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | - Giovanni Fantola
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | | | - Angelo Restivo
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | | | | | - Francesco Cabras
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | - Rossano Ambu
- Department of Pathology, University of Cagliari, Cagliari, Italy
| | - Giuseppe Casula
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
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11
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Egoavil C, Juárez M, Guarinos C, Rodríguez-Soler M, Hernández-Illán E, Alenda C, Payá A, Castillejo A, Serradesanferm A, Bujanda L, Fernández-Bañares F, Cubiella J, de-Castro L, Guerra A, Aguirre E, Herreros-de-Tejada A, Bessa X, Herráiz M, Marín-Gabriel JC, Balmaña J, Piñol V, Rodríguez Moranta F, Nicolás-Pérez D, Cuatrecasas M, Balaguer F, Castells A, Soto JL, Zapater P, Jover R. Increased Risk of Colorectal Cancer in Patients With Multiple Serrated Polyps and Their First-Degree Relatives. Gastroenterology 2017; 153:106-112.e2. [PMID: 28400194 DOI: 10.1053/j.gastro.2017.04.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 04/04/2017] [Accepted: 04/04/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated whether patients with multiple serrated polyps, but not meeting the World Health Organization criteria for serrated polyposis syndrome, and their relatives have similar risks for colorectal cancer (CRC) as those diagnosed with serrated polyposis. METHODS We collected data from patients with more than 10 colonic polyps, recruited in 2008-2009 from 24 hospitals in Spain for a study of causes of multiple colonic polyps. We analyzed data from 53 patients who met the criteria for serrated polyposis and 145 patients who did not meet these criteria, but who had more than 10 polyps throughout the colon, of which more than 50% were serrated. We calculated age- and sex-adjusted standardized incidence ratios (SIRs) for CRC in both groups, as well as in their first-degree relatives. RESULTS The prevalence of CRC was similar between patients with confirmed serrated polyposis and multiple serrated polyps (odds ratio, 1.35; 95% confidence interval [CI], 0.64-2.82; P = .40). The SIR for CRC in patients with serrated polyposis (0.51; 95% CI, 0.01-2.82) did not differ significantly from the SIR for CRC in patients with multiple serrated polyps (0.74; 95% CI, 0.20-1.90; P = .70). The SIR for CRC also did not differ significantly between first-degree relatives of these groups (serrated polyposis: 3.28, 95% CI, 2.16-4.77; multiple serrated polyps: 2.79, 95% CI, 2.10-3.63; P = .50). Kaplan-Meier analysis showed no differences in the incidence of CRC between groups during the follow-up period (log-rank, 0.6). CONCLUSIONS The risk of CRC in patients with multiple serrated polyps who do not meet the criteria for serrated polyposis, and in their first-degree relatives, is similar to that of patients diagnosed with serrated polyposis.
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Affiliation(s)
- Cecilia Egoavil
- Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Miriam Juárez
- Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Carla Guarinos
- Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - María Rodríguez-Soler
- Service of Digestive Medicine, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Eva Hernández-Illán
- Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Cristina Alenda
- Pathology Department, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Artemio Payá
- Pathology Department, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Adela Castillejo
- Molecular Genetics Laboratory, Elche University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Anna Serradesanferm
- Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Luis Bujanda
- Gastroenterology Department, Hospital Donostia, Centros de Investigación Biomédica en Red de enfermedades hepáticas y digestivas, Universidad del País Vasco, San Sebastián, Spain
| | | | - Joaquín Cubiella
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Luisa de-Castro
- Gastroenterology Department, Complexo Hospitalario de Vigo, Vigo, Spain
| | - Ana Guerra
- Gastroenterology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - Elena Aguirre
- Oncology Department, Hospital Arnau de Vilanova, Lleida, Spain
| | | | - Xavier Bessa
- Gastroenterology Department, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Maite Herráiz
- Gastroenterology Department, Clínica Universitaria de Navarra, Pamplona, Spain
| | | | - Judith Balmaña
- Oncology Department, Hospital Vall d'Hebrón, Barcelona, Spain
| | - Virginia Piñol
- Gastroenterology Department, Hospital Universitari Dr. Josep Trueta, Girona, Spain
| | | | - David Nicolás-Pérez
- Gastroenterology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | | | - Francesc Balaguer
- Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - Antoni Castells
- Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic, Barcelona, Spain
| | - José-Luis Soto
- Molecular Genetics Laboratory, Elche University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Pedro Zapater
- Clinical Pharmacology Department, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
| | - Rodrigo Jover
- Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain; Service of Digestive Medicine, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain.
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12
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Kim ER, Jeon J, Lee JH, Lee YJ, Hong SN, Chang DK, Kim YH. Clinical characteristics of patients with serrated polyposis syndrome in Korea: comparison with Western patients. Intest Res 2017; 15:402-410. [PMID: 28670238 PMCID: PMC5478766 DOI: 10.5217/ir.2017.15.3.402] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 05/17/2016] [Accepted: 05/25/2016] [Indexed: 02/07/2023] Open
Abstract
Background/Aims Serrated polyposis syndrome (SPS) has been shown to increase the risk of colorectal cancer (CRC). However, little is known about the characteristics of Asian patients with SPS. This study aimed to identify the clinicopathological features and risk of CRC in Korean patients with SPS as well as the differences between Korean and Western patients based on a literature review. Methods This retrospective study included 30 patients with SPS as defined by World Health Organization classification treated at Samsung Medical Center, Korea, between March 1999 and May 2011. Results Twenty patients (67%) were male. The median patient age at diagnosis was 56 years (range, 39–76 years). A total of 702 polyps were identified during a median follow-up of 43 months (range, 0–149 months). Serrated polyps were noted more frequently in the distal colon (298/702, 55%). However, large serrated polyps and serrated adenomas were mainly distributed throughout the proximal colon (75% vs. 25% and 81% vs. 19%, respectively); 73.3% had synchronous adenomatous polyps. The incidence of CRC was 10% (3/30 patients), but no interval CRC was detected. A total of 87% of the patients underwent esophagogastroduodenoscopy and 19.2% had significant lesions. Conclusions The phenotype of SPS in Korean patients is different from that of Western patients. In Korean patients, SPS is more common in men, there were fewer total numbers of serrated adenoma/polyps, and the incidence of CRC was lower than that in Western patients. Korean patients tend to more frequently have abnormal gastric lesions. However, the prevalence of synchronous adenomatous polyps is high in both Western and Korean patients.
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Affiliation(s)
- Eun Ran Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaryong Jeon
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin Hee Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Jung Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Kyung Chang
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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13
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Abstract
Serrated polyps (SPs) of the colorectum pose a novel challenge to practicing gastroenterologists. Previously thought benign and unimportant, there is now compelling evidence that SPs are responsible for a significant percentage of incident colorectal cancer worldwide. In contrast to conventional adenomas, which tend to be slow growing and polypoid, SPs have unique features that undermine current screening and surveillance practices. For example, sessile serrated polyps (SSPs) are flat, predominately right-sided, and thought to have the potential for rapid growth. Moreover, SSPs are subject to wide variations in endoscopic detection and pathologic interpretation. Unfortunately, little is known about the natural history of SPs, and current guidelines are based largely on expert opinion. In this review, we outline the current taxonomy, epidemiology, and management of SPs with an emphasis on the clinical and public health impact of these lesions.
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Affiliation(s)
| | - Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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14
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IJspeert JEG, Rana SAQ, Atkinson NSS, van Herwaarden YJ, Bastiaansen BAJ, van Leerdam ME, Sanduleanu S, Bisseling TM, Spaander MCW, Clark SK, Meijer GA, van Lelyveld N, Koornstra JJ, Nagtegaal ID, East JE, Latchford A, Dekker E. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut 2017; 66:278-284. [PMID: 26603485 DOI: 10.1136/gutjnl-2015-310630] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 09/23/2015] [Accepted: 10/28/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.
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Affiliation(s)
- J E G IJspeert
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - S A Q Rana
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - N S S Atkinson
- Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Y J van Herwaarden
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - B A J Bastiaansen
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - M E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - S Sanduleanu
- Division of Gastroenterology and Hepatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - T M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - M C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - S K Clark
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - G A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - N van Lelyveld
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - J J Koornstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - J E East
- Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - A Latchford
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - E Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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15
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Carballal S, Rodríguez-Alcalde D, Moreira L, Hernández L, Rodríguez L, Rodríguez-Moranta F, Gonzalo V, Bujanda L, Bessa X, Poves C, Cubiella J, Castro I, González M, Moya E, Oquiñena S, Clofent J, Quintero E, Esteban P, Piñol V, Fernández FJ, Jover R, Cid L, López-Cerón M, Cuatrecasas M, López-Vicente J, Leoz ML, Rivero-Sánchez L, Castells A, Pellisé M, Balaguer F. Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut 2016; 65:1829-1837. [PMID: 26264224 DOI: 10.1136/gutjnl-2015-309647] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 07/08/2015] [Accepted: 07/10/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.
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Affiliation(s)
- Sabela Carballal
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | | | - Leticia Moreira
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Luis Hernández
- Digestive Disease Section, Hospital Universitario de Móstoles, Madrid, Spain
| | - Lorena Rodríguez
- Gastroenterology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | | | - Victoria Gonzalo
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain
| | - Luis Bujanda
- Gastroenterology Department, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Xavier Bessa
- Gastroenterology Department, Hospital del Mar, Barcelona, Spain
| | - Carmen Poves
- Gastroenterology Department, Hospital Clínico de San Carlos, Madrid, Spain
| | - Joaquin Cubiella
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense, Pontevedra y Vigo, Ourense, Spain
| | - Inés Castro
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense, Pontevedra y Vigo, Ourense, Spain
| | - Mariano González
- Gastroenterology Department, Hospital Puerta del Hierro, Madrid, Spain
| | - Eloísa Moya
- Gastroenterology Department, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain
| | - Susana Oquiñena
- Gastroenterology Department, Complejo Hospitalario de Navarra, Navarra, Spain
| | - Joan Clofent
- Gastroenterology Department, Hospital de Sagunto, Sagunto, Valencia, Spain
| | - Enrique Quintero
- Gastroenterology Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Pilar Esteban
- Gastroenterology Department, Hospital Morales Meseguer, Murcia, Spain
| | - Virginia Piñol
- Gastroenterology Department, Hospital Josep Trueta, Girona, Spain
| | | | - Rodrigo Jover
- Gastroenterology Department, Hospital General de Alicante, Alicante, Spain
| | - Lucía Cid
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomedica Ourense, Pontevedra, y Vigo, Vigo, Spain
| | - María López-Cerón
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre for Biomedical Diagnosis, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Jorge López-Vicente
- Digestive Disease Section, Hospital Universitario de Móstoles, Madrid, Spain
| | - Maria Liz Leoz
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Liseth Rivero-Sánchez
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - María Pellisé
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
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16
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Bejarano PA, Garcia-Buitrago MT, Berho M, Allende D. Biologic and molecular markers for staging colon carcinoma. COLORECTAL CANCER 2016. [DOI: 10.2217/crc.15.27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Biomarkers in the field of pathology and oncology may allow for the detection of disease, assessment of prognosis or to predict response to certain therapy. Molecular abnormalities in colorectal cancer genesis may occur due to chromosome instability, microsatellite instability and DNA methylation (CpG island methylator phenotype). These alterations are associated in some cases to sporadic carcinomas whereas in others are seen in syndrome-related tumors and are the basis for the use of different biomarkers in the clinical setting. These may include mismatched repair gene/proteins, RAS, BRAF, PIK3CA, which help to determine tumor prognosis and predict response to certain drugs.
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Affiliation(s)
- Pablo A Bejarano
- Department of Pathology Cleveland Clinic Florida, 2900 Weston Road, Weston, FL 33331, USA
| | - Monica T Garcia-Buitrago
- Department of Pathology, University of Miami School of Medicine, 1611 NW 12 Ave. Holtz Bldg, Miami, FL 33136, USA
| | - Mariana Berho
- Department of Pathology Cleveland Clinic Florida, 2900 Weston Road, Weston, FL 33331, USA
| | - Daniela Allende
- Department of Pathology Cleveland Clinic, Cleveland, OH 9500 Euclid Avenue Cleveland, OH 44195, USA
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17
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Yang HM, Mitchell JM, Sepulveda JL, Sepulveda AR. Molecular and histologic considerations in the assessment of serrated polyps. Arch Pathol Lab Med 2015; 139:730-41. [PMID: 26030242 DOI: 10.5858/arpa.2014-0424-ra] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
UNLABELLED CONTEXT : Colorectal cancer is a heterogeneous disease resulting from different molecular pathways of carcinogenesis. Recent data evaluating the histologic features and molecular basis of the serrated polyp-carcinoma pathway have significantly contributed to more comprehensive classifications of and treatment recommendations for these tumors. OBJECTIVE To integrate the most recent molecular findings in the context of histologic classifications of serrated lesions and their implications in diagnostic pathology and colorectal cancer surveillance. DATA SOURCES Published literature focused on serrated polyps and their association with colorectal cancer. CONCLUSIONS Three types of serrated polyps are currently recognized: hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. The BRAF V600E mutation is one of the most frequent molecular abnormalities identified in hyperplastic polyps and sessile serrated adenomas. In contrast, in traditional serrated adenomas, either BRAF V600E or KRAS mutations can be frequently identified. CpG methylation has emerged as a critical molecular mechanism in the sessile serrated pathway. CpG methylation of MLH1 often leads to reduced or lost expression in dysplastic foci and carcinomas arising in sessile serrated adenomas/polyps.
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Affiliation(s)
- Hui-Min Yang
- From the Department of Pathology and Cell Biology, Columbia University, New York, New York
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18
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Edelstein DL, Cruz-Correa M, Soto-Salgado M, Axilbund JE, Hylind LM, Romans K, Blair C, Wiley E, Tersmette AC, Offerhaus JA, Giardiello FM. Risk of Colorectal and Other Cancers in Patients With Serrated Polyposis. Clin Gastroenterol Hepatol 2015; 13:1697-9. [PMID: 25681317 PMCID: PMC4532657 DOI: 10.1016/j.cgh.2015.02.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 01/31/2015] [Accepted: 02/02/2015] [Indexed: 02/02/2023]
Abstract
Patients with serrated polyposis develop multiple colorectal hyperplastic and/or serrated sessile adenomas/polyps. We investigated the risk of colorectal and other cancers by analyzing data from 64 patients with serrated polyposis (mean age at diagnosis, 54 y; 41% men; 92% white) listed in the Johns Hopkins Polyposis Registry. Medical, endoscopic, and histopathology reports were evaluated. Six patients (9.4%) had a history of colorectal cancer, diagnosed at a mean age of 56 years; 6 additional patients (9.4%) had at least 1 advanced colorectal adenoma. Extracolonic cancers were found in 16% of the study population. The standard incidence ratio for colorectal cancer in patients with serrated polyposis was 18.72 (95% confidence interval, 6.87-40.74) and for extracolonic cancer was 31.20 (95% confidence interval, 14.96-57.37), compared with the Surveillance, Epidemiology, and End Results population. Patients with serrated polyposis therefore have a high risk for colorectal cancer and require vigilant colorectal surveillance, starting at the time of diagnosis of serrated polyposis. The risk of extracolonic cancer also appears to be increased, but this requires further evaluation.
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Affiliation(s)
- Daniel L Edelstein
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Marcia Cruz-Correa
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, University of Puerto Rico/MD Anderson Cancer Center Partnership for Excellence in Cancer Research, San Juan, Puerto Rico
| | | | - Jennifer E Axilbund
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Linda M Hylind
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Katharine Romans
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Cherie Blair
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elizabeth Wiley
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | - Francis M Giardiello
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
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19
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Pyleris E, Koutsounas IS, Karantanos P. Three Colon Adenocarcinomas Arising in a Patient with Serrated Polyposis Syndrome: Case Report and Review of the Literature. VISZERALMEDIZIN 2015; 30:136-9. [PMID: 26286237 PMCID: PMC4513800 DOI: 10.1159/000360386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background Serrated polyposis syndrome (SPS) is a rare entity mainly concerning the 6th decade of life and which is characterized by the presence of multiple large hyperplastic polyps, sessile serrated adenomas, and adenomas within the colon. Case Report We describe the case of a SPS patient with 3 synchronous adenocarcinomas. The morphologic features of serrated colorectal lesions, their characteristic molecular alterations, and their role in colorectal cancer development are discussed herein. Conclusion Our findings suggest that SPS is a rare condition with an increased risk for colon cancer. Patients suffering from SPS should have regular colonoscopic surveillance, and perhaps those with numerous dysplastic hyperplastic polyps should be treated with colectomy.
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Affiliation(s)
- Emmanouil Pyleris
- Department of Gastroenterology and Endoscopy Unit, Sismanogleion General Hospital, Marousi, Greece
| | - Ioannis S Koutsounas
- Department of Gastroenterology and Endoscopy Unit, Sismanogleion General Hospital, Marousi, Greece
| | - Panagiotis Karantanos
- Department of Gastroenterology and Endoscopy Unit, Sismanogleion General Hospital, Marousi, Greece
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20
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Abstract
Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding pathogenesis and clinical behaviour. Four decades ago, the adenoma-carcinoma pathway was presented as the main pathway towards CRC, a conclusion that was largely based on evidence from observational morphological studies. This concept was later substantiated at the genomic level. Over the past decade, evidence has been generated for alternative routes in which CRC might develop, in particular the serrated neoplasia pathway. Providing indisputable evidence for the neoplastic potential of serrated polyps has been difficult. Reasons include the absence of reliable longitudinal observations on individual serrated lesions that progress to cancer, a shortage of available animal models for serrated lesions and challenging culture conditions when generating organoids of serrated lesions for in vitro studies. However, a growing body of circumstantial evidence has been accumulated, which indicates that ≥15% of CRCs might arise through the serrated neoplasia pathway. An even larger amount of post-colonoscopy colorectal carcinomas (carcinomas occurring within the surveillance interval after a complete colonoscopy) have been suggested to originate from serrated polyps. The aim of this Review is to assess the current status of the serrated neoplasia pathway in CRC and highlight clinical implications.
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21
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Sreedharanunni S, Paulose R, Jojo A, Dhar P, Gangadharan P. Colonic polyposis syndromes--an experience from a tertiary centre in South India. Indian J Gastroenterol 2015; 34:233-9. [PMID: 25957234 DOI: 10.1007/s12664-015-0558-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2015] [Accepted: 04/01/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several polyposis syndromes of the gastrointestinal tract have been recognized which carry increased risk for cancer and have a genetic predisposition. There is a paucity of literature regarding the occurrence and the burden of colonic polyposis syndromes in the Indian subcontinent. This study attempts to highlight this hitherto unaddressed burden and the associated increased risk for inherited colonic cancer in this geographical location. METHODS A retrospective study of various colonic polyposis syndromes encountered at a tertiary centre in South India over a period of 8 years (2005 to 2012) was performed. The diagnosis in each case was made histologically with clinicopathological correlation. RESULTS Fifty cases were identified as belonging to a colonic polyposis syndrome, during the study period. There were 27 males and 23 females with a median age of 36.5 years (range 19 months to 78 years). The commonest syndrome was familial adenomatous polyposis (n = 27; 54 %) followed by Peutz-Jeghers syndrome (n = 11), attenuated familial adenomatous polyposis (n = 7), juvenile polyposis syndrome (n = 3), hyperplasic polyposis syndrome (n = 1) and Cronkhite-Canada syndrome (n = 1). Colonic malignancy was documented at first presentation in 22 patients (44 %). CONCLUSIONS Our study highlights the various colonic polyposis syndromes encountered in a tertiary care institution in Southern India.
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Affiliation(s)
- Sreejesh Sreedharanunni
- Department of Pathology, Amrita Institute of Medical Sciences, Ponekkara, Kochi, 682 041, India
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22
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Feuerstein JD, Flier SN, Yee EU, Pleskow D, Cheifetz AS. A rare case series of concomitant inflammatory bowel disease, sporadic adenomas, and serrated polyposis syndrome. J Crohns Colitis 2014; 8:1735-1739. [PMID: 25047878 DOI: 10.1016/j.crohns.2014.07.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 06/27/2014] [Accepted: 07/02/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) involving the colon is associated with an increased risk of colon cancer. Patients may develop sporadic adenomas further increasing their risk of colorectal cancer. Current knowledge of IBD with concomitant serrated polyposis syndrome (SPS) is limited. We describe four patients with both IBD and SPS. METHODS Four patients with inflammatory bowel disease and hyperplastic polyps referred to Beth Israel Deaconess Medical Center meeting the World Health Organization (WHO) criteria for SPS were identified. RESULTS Four patients with long standing IBD involving the colon were identified. All of these patients' IBD were in clinical remission. Additionally, 2 of the 4 patients were also noted to have sporadic adenomas. Each patient was also found to have multiple sessile serrated adenomas and hyperplastic polyps meeting the WHO criteria for SPS. Two of the patients had colonoscopy with chromoendoscopy which improved polyp detection. Discussions were held with each patient regarding the potentially increased risk of colorectal cancer with the combination of IBD and SPS. Patients were advised that colectomy would be the safest method to reduce the risk of cancer. None of the patients opted for colectomy and instead planned on a repeat colonoscopy with chromoendoscopy at 3-12 month intervals. CONCLUSION Serrated polyposis syndrome develops in patients with IBD. It is unclear how high the risk of colon cancer is in patients who have both IBD and SPS and what the recommendations should be regarding the frequency of surveillance or surgery. Further studies are necessary to identify the optimal management of these patients.
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Affiliation(s)
- J D Feuerstein
- 330 Brookline Ave. E/Dana 501, Boston, MA 02215, United States; Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
| | - S N Flier
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
| | - E U Yee
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
| | - D Pleskow
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
| | - A S Cheifetz
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
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Toyoshima N, Sakamoto T, Makazu M, Nakajima T, Matsuda T, Kushima R, Shimoda T, Fujii T, Inoue H, Kudo SE, Saito Y. Prevalence of serrated polyposis syndrome and its association with synchronous advanced adenoma and lifestyle. Mol Clin Oncol 2014; 3:69-72. [PMID: 25469272 DOI: 10.3892/mco.2014.423] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 09/12/2014] [Indexed: 12/30/2022] Open
Abstract
We assessed the clinicopathological characteristics of patients with serrated polyposis syndrome (SPS) and the incidence of advanced adenoma/colorectal cancer (CRC). We prospectively enrolled 249 consecutive patients who underwent colonoscopy at the National Cancer Center Hospital over a 6-month period. All the polyps were diagnosed using magnification colonoscopy and resection/biopsy. The enrolled patients were divided into two groups, i) those with ≥5 histologically diagnosed hyperplastic polyps (HPs) proximal to the sigmoid colon, with at least 2 polyps >10 mm in diameter and ii) those with ≥20 HPs distributed throughout the colon. The clinical characteristics of the two groups were compared, including lifestyle, family history of CRC and colonoscopic findings. HPs were identified in 228 patients, of whom 21 (8.4%) had SPS. All 21 patients had ≥20 HPs distributed throughout the colon, with none having >2 HPs ≥1 cm in diameter in the right colon. Synchronous advanced adenoma/CRC was diagnosed in 76/249 (30.5%) patients. The prevalence of advanced adenoma/CRC was higher among patients with compared to those without SPS (P=0.075). SPS was also associated with older age and higher body mass index (BMI). Our results suggested that older age and higher BMI are independent risk factors for SPS. Advanced adenoma/CRC tended to occur more frequently among patients with compared to those without SPS, although the difference was not statistically significant.
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Affiliation(s)
- Naoya Toyoshima
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan ; Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Taku Sakamoto
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Makomo Makazu
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Takeshi Nakajima
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Takahisa Matsuda
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Ryoji Kushima
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0045, Japan
| | - Tadakazu Shimoda
- Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104-0061, Japan
| | | | - Haruhiro Inoue
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa 224-8503, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
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24
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Valle L. Genetic predisposition to colorectal cancer: Where we stand and future perspectives. World J Gastroenterol 2014; 20:9828-9849. [PMID: 25110415 PMCID: PMC4123366 DOI: 10.3748/wjg.v20.i29.9828] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 02/10/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
The development of colorectal cancer (CRC) can be influenced by genetic factors in both familial cases and sporadic cases. Familial CRC has been associated with genetic changes in high-, moderate- and low-penetrance susceptibility genes. However, despite the availability of current gene-identification techniques, the genetic causes of a considerable proportion of hereditary cases remain unknown. Genome-wide association studies of CRC have identified a number of common low-penetrance alleles associated with a slightly increased or decreased risk of CRC. The accumulation of low-risk variants may partly explain the familial risk of CRC, and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance genes. Understanding the predisposition to develop CRC will require investigators to address the following challenges: the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis; the classification of variants of unknown significance in known CRC-predisposing genes; and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation carriers. We performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of low- and moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene approaches. Current challenges and future perspectives in the field of CRC predisposition are also discussed.
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25
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I Young J, Hooper JE, Lu KC, Herzig DO, Tsikitis VL. Serrated polyposis syndrome. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Serrated polyposis syndrome, also called hyperplastic polyposis, is a condition characterized by numerous neoplastic polyps throughout the colon and rectum. The polyps possess a distinct serrated morphology. The term serrated refers to the ‘saw-tooth’ pattern formed by epithelial cells in the colonic crypts on standard histologic preparations. Historically, serrated lesions have been lumped together under the term ‘hyperplastic polyps’, and were assumed to carry no malignant potential. Over the past decade, however, an increasing body of evidence suggests that serrated lesions exist along a spectrum and represent an alternative molecular pathway to the development of colorectal cancer in contrast to the traditional adenocarcinoma sequence. Although a hallmark genetic signature for serrated polyposis syndrome remains unidentified, this is an area of active investigation.
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Affiliation(s)
- John I Young
- Division of General & Gastrointestinal Surgery, Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA
| | - Jody E Hooper
- Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA
| | - Kim C Lu
- Division of General & Gastrointestinal Surgery, Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA
| | - Daniel O Herzig
- Division of General & Gastrointestinal Surgery, Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA
| | - Vassiliki L Tsikitis
- Division of General & Gastrointestinal Surgery, Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA
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26
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Hazewinkel Y, Tytgat KMAJ, van Eeden S, Bastiaansen B, Tanis PJ, Boparai KS, Fockens P, Dekker E. Incidence of colonic neoplasia in patients with serrated polyposis syndrome who undergo annual endoscopic surveillance. Gastroenterology 2014; 147:88-95. [PMID: 24657624 DOI: 10.1053/j.gastro.2014.03.015] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 03/09/2014] [Accepted: 03/14/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with serrated polyposis syndrome (SPS) are advised to undergo endoscopic surveillance for early detection of polyps and prevention of colorectal cancer (CRC). The optimal surveillance and treatment regimen is unknown. We performed a prospective study to evaluate a standardized endoscopic treatment protocol in a large cohort of patients with SPS. METHODS We followed a cohort of patients with SPS who received annual endoscopic surveillance at the Academic Medical Centre in Amsterdam, The Netherlands from January 2007 through December 2012. All patients underwent clearing colonoscopy with removal of all polyps ≥3 mm. After clearance, subsequent follow-up colonoscopies were scheduled annually. The primary outcomes measure was the incidence of CRC and polyps. Secondary outcomes were the incidence of complications and the rate of preventive surgery. RESULTS Successful endoscopic clearance of all polyps ≥3 mm was achieved in 41 of 50 (82%) patients. During subsequent annual surveillance, with a median follow-up time of 3.1 years (interquartile range, 1.5-4.3 years), CRC was not detected. The cumulative risks of detecting CRC, advanced adenomas, or large (≥10 mm) serrated polyps after 3 surveillance colonoscopies were 0%, 9%, 34%, respectively. Twelve patients (24%) were referred for preventive surgery; 9 at initial colonoscopy and 3 during surveillance. Perforations or severe bleeding did not occur. CONCLUSIONS Annual surveillance with complete removal of all polyps ≥3 mm with timely referral of selected high-risk patients for prophylactic surgery prevents development of CRC in SPS patients without significant morbidity. Considering the substantial risk of polyp recurrence, close endoscopic surveillance in SPS seems warranted. www.trialregister.nl ID NTR2757.
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Affiliation(s)
- Yark Hazewinkel
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Kristien M A J Tytgat
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Susanne van Eeden
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - Barbara Bastiaansen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Karam S Boparai
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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27
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Lucci-Cordisco E, Risio M, Venesio T, Genuardi M. The growing complexity of the intestinal polyposis syndromes. Am J Med Genet A 2013; 161A:2777-87. [PMID: 24124059 DOI: 10.1002/ajmg.a.36253] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Accepted: 09/05/2013] [Indexed: 12/12/2022]
Abstract
Familial adenomatous polyposis has been the first form of inherited intestinal polyposis to be recognized. For a long time it has been considered the main polyposis syndrome, associated with an easily recognizable phenotype, with a marginal role attributed to a few very rare hamartomatous conditions. More recently, it has been gradually demonstrated that the intestinal polyposes encompass a range of conditions within a wide spectrum of disease severity, polyp histology, and extraintestinal manifestations. A growing number of genes and phenotypes has been identified, and heterogeneity of somatic molecular pathways underlying epithelial transformation in different syndromes and associated tumors has been documented. Increasing knowledge on the molecular bases and more widespread use of genetic tests has shown phenotypic overlaps between conditions that were previously considered distinct, highlighting diagnostic difficulties. With the advent of next generation sequencing, the diagnosis and the classification of these syndromes will be progressively based more on genetic testing results. However, the phenotypic variability documented among patients with mutations in the same genes cannot be fully explained by different expressivity, indicating a role for as yet unknown modifying factors. Until the latter will be identified, the management of patients with polyposis syndromes should be guided by both clinical and genetic findings.
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Affiliation(s)
- Emanuela Lucci-Cordisco
- Institute of Medical Genetics, "A. Gemelli" School of Medicine, Catholic University, Rome, Italy
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28
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Sweetser S, Smyrk TC, Sinicrope FA. Serrated colon polyps as precursors to colorectal cancer. Clin Gastroenterol Hepatol 2013; 11:760-7; quiz e54-5. [PMID: 23267866 PMCID: PMC3628288 DOI: 10.1016/j.cgh.2012.12.004] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 11/27/2012] [Accepted: 12/07/2012] [Indexed: 02/07/2023]
Abstract
Identification of the serrated neoplasia pathway has improved our understanding of the pathogenesis of colorectal cancer (CRC). Insights include an increased recognition of the malignant potential of different types of serrated polyps such as sessile and traditional serrated adenomas. Sessile serrated adenomas share molecular features with colon tumors that have microsatellite instability and a methylator phenotype, indicating that these lesions are precursors that progress via the serrated neoplasia pathway. These data have important implications for clinical practice and CRC prevention, because hyperplastic polyps were previously regarded as having no malignant potential. There is also evidence that the serrated pathway contributes to interval or missed cancers. Endoscopic detection of serrated polyps is a challenge because they are often inconspicuous with indistinct margins and are frequently covered by adherent mucus. It is important for gastroenterologists to recognize the subtle endoscopic features of serrated polyps to facilitate their detection and removal, and thereby ensure a high-quality colonoscopic examination. Recognition of the role of serrated polyps in colon carcinogenesis has led to the inclusion of these lesions in postpolypectomy surveillance guidelines. However, an enhanced effort is needed to identify and completely remove serrated adenomas, with the goal of increasing the effectiveness of colonoscopy to reduce CRC incidence.
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Affiliation(s)
- Seth Sweetser
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
| | - Thomas C. Smyrk
- Division of Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, MN
| | - Frank A. Sinicrope
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
- Division of Oncology, Mayo Clinic College of Medicine, Rochester, MN
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29
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Serrated lesions and hyperplastic (serrated) polyposis relationship with colorectal cancer: classification and surveillance recommendations. Gastrointest Endosc 2013; 77:858-71. [PMID: 23684091 DOI: 10.1016/j.gie.2013.02.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 02/11/2013] [Indexed: 02/08/2023]
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Guarinos C, Sánchez-Fortún C, Rodríguez-Soler M, Pérez-Carbonell L, Egoavil C, Juárez M, Serradesanferm A, Bujanda L, Fernández-Bañares F, Cubiella J, de-Castro L, Guerra A, Aguirre E, Herreros-de-Tejada A, Bessa X, Herráiz M, Marín-Gabriel JC, Balmaña J, Cuatrecasas M, Balaguer F, Castells A, Soto JL, Alenda C, Payá A, Jover R. Clinical subtypes and molecular characteristics of serrated polyposis syndrome. Clin Gastroenterol Hepatol 2013; 11:705-e46. [PMID: 23376323 DOI: 10.1016/j.cgh.2012.12.045] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Revised: 12/17/2012] [Accepted: 12/21/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated clinical and molecular differences between the different phenotypes of serrated polyposis syndrome (SPS) and the frequency of mutations in BRAF or KRAS in polyps from patients with SPS. METHODS We collected data on clinical and demographic characteristics of 50 patients who fulfilled the criteria for SPS. Polymerase chain reaction and sequence analysis were used to identify BRAF and KRAS mutations in 432 polyps collected from 37 patients; we analyzed CpG island methylator phenotypes in 272 of these polyps. RESULTS Fifteen patients (30%) had type 1 SPS and 35 had type 2 SPS. There were no significant differences in age at diagnosis, sex, smoking frequency, body mass index, or colorectal cancer predisposition between groups of patients, or in the pathologic or molecular characteristics of their polyps. A familial history of colorectal cancer or colonic polyps was reported more frequently by patients with type 2 SPS. BRAF mutations were found in 63% of polyps and KRAS mutations were found in 9.9%; 43.4% of polyps had the CpG island methylator phenotype-high phenotype. A per-patient analysis revealed that all patients had a BRAF or KRAS mutation in more than 25% of their polyps; 84.8% of patients had a mutation in BRAF or KRAS in more than 50% of their polyps. CONCLUSIONS Except for a greater likelihood of familial history of colorectal cancer or colonic polyps in patients with type 2 SPS, we found no significant demographic, pathologic, or molecular differences between types 1 and 2 SPS. All patients had a BRAF or KRAS mutation in at least 25% of their polyps.
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Affiliation(s)
- Carla Guarinos
- Unidad de Investigación, Hospital General Universitario de Alicante, Alicante, Spain
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Carballal S, Moreira L, Balaguer F. Pólipos serrados y síndrome de poliposis serrada. Cir Esp 2013; 91:141-8. [DOI: 10.1016/j.ciresp.2012.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Revised: 11/15/2012] [Accepted: 12/01/2012] [Indexed: 12/23/2022]
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Abstract
INTRODUCTION Serrated polyposis (SP) is an infrequent colorectal cancer (CRC) predisposition syndrome. An unidentified genetic defect is believed to play a role in this condition. The risk of SP and/or CRC for first-degree relatives (FDRs) is not yet well known. The aim of our study was to determine the incidence of both SP and/or CRC by studying the FDRs of our index SP cases and to propose an appropriate interval for colonoscopy surveillance in this group. METHODS From 2005 to December 2011, we prospectively included all patients from our hospital who fulfilled the SP diagnostic criteria. We interviewed FDRs face to face and offered a colonoscopy to those who were 35 years old or older. The study was carried out with conventional and high-definition colonoscopes and chromoendoscopy with indigo carmine at the discretion of a single endoscopist. The samples were assessed by two pathologists. We reviewed the clinical data for CRC diagnosed previously in FDRs. RESULTS From 2005, we collected all the new cases of SP and offered a colonoscopy to 95 FDRs of 34 pedigrees. We performed colonoscopies on 78 FDRs (82.1%). The incidence of SP in the FDRs was 32% (25 patients). Seventy-six percent of patients were diagnosed with SP as they had any number of serrated polyps proximal to the sigmoid colon. Only one patient was diagnosed with CRC as a result of the screening colonoscopy. 44.1% of our index cases had an FDR with a diagnosis of CRC. CONCLUSION Our series, which is the largest prospective cohort of FDRs published, reports an elevated incidence of SP in FDRs, thus supporting the need for screening colonoscopy in FDR and its inclusion in the guidelines.
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Serrated polyposis is an underdiagnosed and unclear syndrome: the surgical pathologist has a role in improving detection. Am J Surg Pathol 2012; 36:1178-85. [PMID: 22790859 DOI: 10.1097/pas.0b013e3182597f41] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Serrated polyposis syndrome (SPS) is poorly defined and patients have an increased but unspecified risk for colorectal carcinoma through the serrated pathway. Despite this association SPS remains relatively obscure and is therefore likely underrecognized. We determined the frequency of SPS among patients with any serrated polyps (SPs) over a 6-month "index" period, and in doing so we assessed the ability of surgical pathologists to improve SPS detection. Particular attention was given to the index procedure to assess the potential predictive value of the findings resulting from a single colonoscopy. A total of 929 patients with at least 1 SP were identified, 17 of whom (1.8%) were determined to meet World Health Organization criteria for SPS. Nine patients met the first criterion (≥ 5 proximal SPs, 2 of which are > 10 mm); 4 met the third criterion (> 20 SPs of any size distributed throughout the colon); and 4 met both criteria. Although no specific SP size or number at the index procedure was clearly superior in its ability to predict SPS, > 50% of cases would be detected if a cutoff of ≥ 3 SPs or a single SP ≥ 15 mm at the index procedure is used. In summary, SPS is rare but more likely underdiagnosed. Additional studies to address the underlying genetic basis for SPS are ongoing in order to shed further light on this syndrome. Surgical pathologists are in a unique position to assist in this endeavor by identifying those patients who either meet or seem to be at high risk of meeting World Health Organization criteria.
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Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, Goldblum JR, Guillem JG, Kahi CJ, Kalady MF, O’Brien MJ, Odze RD, Ogino S, Parry S, Snover DC, Torlakovic EE, Wise PE, Young J, Church J. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012; 107:1315-29; quiz 1314, 1330. [PMID: 22710576 PMCID: PMC3629844 DOI: 10.1038/ajg.2012.161] [Citation(s) in RCA: 827] [Impact Index Per Article: 63.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
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Affiliation(s)
| | - Dennis J. Ahnen
- Staff Physician Denver VA Medical Center and Professor of Medicine, University of Colorado School of Medicine
| | | | | | - Carol A. Burke
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Randall W. Burt
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine
| | | | | | - Charles J. Kahi
- Indiana University School of Medicine; Richard L. Roudebush VA Medical Center
| | | | | | - Robert D. Odze
- Brigham and Womens Hospital, Department of Pathology, Harvard Medical School, Boston MA
| | - Shuji Ogino
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Susan Parry
- New Zealand Familial GI Cancer Registry, Auckland City Hospital, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
| | - Dale C. Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, MN
| | - Emina Emilia Torlakovic
- Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Paul E. Wise
- Department of Surgery, Vanderbilt University Medical Center
| | - Joanne Young
- Cancer Council Queensland Senior Research Fellow, Laboratory Head, Familial Cancer Laboratory, Australia
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Vemulapalli KC, Rex DK. Failure to recognize serrated polyposis syndrome in a cohort with large sessile colorectal polyps. Gastrointest Endosc 2012; 75:1206-10. [PMID: 22425271 DOI: 10.1016/j.gie.2012.01.033] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Accepted: 01/23/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Serrated polyposis syndrome (SPS) is a rare condition of multiple serrated colorectal polyps and cancers. Colorectal cancer risk is increased in SPS. OBJECTIVE We determined the prevalence of SPS in a cohort of patients with large (≥ 2 cm) sessile colorectal polyps and the rate at which the diagnosis was made by the clinicians. DESIGN Review of patient care database. The 2010 World Health Organization (WHO) criteria were used to identify cases of SPS. SETTING Tertiary academic center. PATIENTS 529 consecutive patients referred for endoscopic resection of a sessile colorectal polyp ≥ 2 cm. MAIN OUTCOME MEASUREMENTS Prevalence of SPS in the cohort and frequency with which the referring physician and the endoscopist recognized SPS. RESULTS Of the 529 patients, 20 (4%) met the WHO criteria for SPS. Only 1 of these cases was suspected by a referring physician. Twelve cases (60%) were either diagnosed or suspected by the endoscopist at our center. Compared with all other patients without SPS, those with SPS were more likely to have an index lesion (the lesion that led to referral) that was serrated (60% vs 3.8%), to have a cecal or ascending colon index lesion (70% vs 45%), and to be current smokers (42% vs 15%). Including the first colonoscopy to remove the index lesion and 26 follow-up colonoscopies, the endoscopist at our center removed 183 serrated polyps from the 20 patients with SPS; of those polyps, 68 were >1 cm. Three patients were referred for surgical resection of involved colon. Eighteen of the 20 patients with SPS met the WHO criterion of 5 serrated polyps proximal to the sigmoid, of which 2 are >1 cm. Failure to recognize SPS by the referring physician was at least partly related to unrecognized serrated lesions. Failure to recognize SPS by the endoscopist at our institution was the result of not systematically applying WHO criteria to the polyp findings. LIMITATIONS Retrospective study. CONCLUSIONS SPS was common in a cohort of patients with large sessile colorectal polyps, and it was frequently unrecognized. These data suggest the need for better detection of serrated lesions, better awareness of SPS, and more consistent application of SPS criteria to the polyp findings of individual patients.
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Affiliation(s)
- Krishna C Vemulapalli
- Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Guarinos C, Sánchez-Fortún C, Rodríguez-Soler M, Alenda C, Payá A, Jover R. Serrated polyposis syndrome: Molecular, pathological and clinical aspects. World J Gastroenterol 2012; 18:2452-61. [PMID: 22654442 PMCID: PMC3360443 DOI: 10.3748/wjg.v18.i20.2452] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2011] [Revised: 02/08/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
Hyperplastic polyps have traditionally been considered not to have malignant potential. New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area. Until recently, it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene, but it has been found that this pathway accounts for only approximately 70%-80% of colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability. The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon. Clinical characteristics, etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet. Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described. Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer. In this review, we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.
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Boparai KS, Hazewinkel Y, Dekker E. Serrated polyposis syndrome and the role of serrated polyps in colorectal cancer development. COLORECTAL CANCER 2012. [DOI: 10.2217/crc.11.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Serrated polyposis syndrome is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer risk. The mixture of distinct precursor lesion types and malignancies in serrated polyposis syndrome provides a unique model to study the recently proposed serrated neoplasia pathway. This pathway involves the progression of serrated polyps, that is, hyperplastic polyps, sessile serrated adenoma/polyps and/or traditional serrated adenomas, to colorectal cancer. The early genetic events of this route, as currently identified, are BRAF or KRAS mutations and an enhanced CPG island methylation status of multiple genes. There is evidence to suggest that a proportion of sporadic colorectal cancers originate from serrated polyps, which encompass molecular sequences of events such as hypermethylation of different genes and BRAF mutations. This review discusses the characteristics and clinical relevance of serrated polyps and provides an overview of the clinical aspects and treatment of serrated polyposis syndrome.
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Affiliation(s)
- Karam Singh Boparai
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Yark Hazewinkel
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
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38
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Abstract
Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.
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Boparai KS, Dekker E, Polak MM, Musler AR, van Eeden S, van Noesel CJM. A serrated colorectal cancer pathway predominates over the classic WNT pathway in patients with hyperplastic polyposis syndrome. THE AMERICAN JOURNAL OF PATHOLOGY 2011; 178:2700-7. [PMID: 21641392 DOI: 10.1016/j.ajpath.2011.02.023] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2010] [Revised: 02/10/2011] [Accepted: 02/22/2011] [Indexed: 12/14/2022]
Abstract
Hyperplastic polyposis syndrome (HPS) is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer (CRC) risk. The mixture of distinct precursor lesion types and malignancies in HPS provides a unique model to study the canonical pathway and a proposed serrated CRC pathway in humans. To establish which CRC pathways play a role in HPS and to obtain new support for the serrated CRC pathway, we assessed the molecular characteristics of polyps (n = 84) and CRCs (n = 19) in 17 patients with HPS versus control groups of various sporadic polyps (n = 59) and sporadic microsatellite-stable CRCs (n = 16). In HPS and sporadic polyps, APC mutations were exclusively identified in adenomas, whereas BRAF mutations were confined to serrated polyps. Six of 19 HPS CRCs (32%) were identified in a serrated polyp. Mutation analysis performed in the CRC and the serrated component of these lesions showed identical BRAF mutations. One HPS CRC was located in an adenoma, both components harboring an identical APC mutation. Overall, 10 of 19 HPS CRCs (53%) carried a BRAF mutation versus none in control group CRCs (P = 0.001). Six BRAF-mutated HPS CRCs (60%) were microsatellite unstable owing to MLH1 methylation. These findings provide novel supporting evidence for the existence of a predominant serrated CRC pathway in HPS, generating microsatellite-stable and microsatellite-instable CRCs.
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Affiliation(s)
- Karam S Boparai
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Rosty C, Parry S, Young JP. Serrated polyposis: an enigmatic model of colorectal cancer predisposition. PATHOLOGY RESEARCH INTERNATIONAL 2011; 2011:157073. [PMID: 21660283 PMCID: PMC3109311 DOI: 10.4061/2011/157073] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2010] [Revised: 02/12/2011] [Accepted: 02/25/2011] [Indexed: 01/30/2023]
Abstract
Serrated polyposis has only recently been accepted as a condition which carries an increased personal and familial risk of colorectal cancer. Described over four decades ago, it remains one of the most underrecognized and poorly understood of all the intestinal polyposes. With a variety of phenotypic presentations, it is likely that serrated polyposis represents a group of diseases rather than a single entity. Further, neoplastic progression in serrated polyposis may be associated with premature aging in the normal mucosa, typified by widespread gene promoter hypermethylation. From this epigenetically altered field, arise diverse polyps and cancers which show a range of molecular features. Despite a high serrated polyp count, only one-third of colorectal cancers demonstrate a BRAF V600E mutation, the molecular hallmark of the canonical serrated pathway, suggesting that though multiple serrated polyps act as a marker of an abnormal mucosa, the majority of CRC in these patients arise within lesions other than BRAF-mutated serrated polyps.
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Affiliation(s)
- Christophe Rosty
- Pathology Queensland and UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia
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41
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Migliore L, Migheli F, Spisni R, Coppedè F. Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol 2011; 2011:792362. [PMID: 21490705 PMCID: PMC3070260 DOI: 10.1155/2011/792362] [Citation(s) in RCA: 172] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2010] [Accepted: 12/14/2010] [Indexed: 12/17/2022] Open
Abstract
Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80-85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype.
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Affiliation(s)
- Lucia Migliore
- Department of Human and Environmental Sciences, University of Pisa, Street S. Giuseppe 22, 56126 Pisa, Italy.
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Abstract
BACKGROUND Hyperplastic polyposis syndrome is a rare syndrome of colorectal cancer predisposition. Patterns of inheritance of hyperplastic polyposis syndrome are not obvious and the clinical definition is relatively arbitrary. We hypothesize that there are multiple phenotypes included in what is currently called hyperplastic polyposis syndrome. We performed this review of a large series of patients who presented with multiple serrated polyps to look for clinical patterns that may confirm our hypothesis. METHODS Hereditary colorectal cancer, colonoscopy, and clinical databases from a single institution were queried for patients meeting the following criteria: 1) ≥ 20 serrated colorectal polyps; 2) ≥ 5 serrated polyps proximal to the sigmoid; 3) ≥ 2 serrated polyps ≥ 10 mm in size; 4) any serrated polyps in a person with at least one first-degree relative who has hyperplastic polyposis syndrome. Records were reviewed for demographics, polyp details, and personal or family history of colorectal extracolonic malignancy. RESULTS One-hundred fifteen patients were included. Median age at diagnosis was 62 years and 56% were male. Ninety-seven percent were white. Twenty-five percent of patients had a personal history and 38% had a family history of colorectal cancer. Twenty-eight percent of patients had a personal history and 54% had a family history of extracolonic cancer. Phenotype analysis identified 3 patterns: relatively few large, right-sided polyps (n = 55), many small left-sided polyps (n = 18), and a combination of both left- and right-sided polyps (n = 42). The right-sided phenotype had more sessile serrated polyps and tended to develop colorectal cancer at a younger age. CONCLUSIONS There are at least 3 different but overlapping clinical phenotypes within hyperplastic polyposis. Recognizing this clinical heterogeneity is important in defining underlying genetic causes.
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Huang CS, Farraye FA, Yang S, O'Brien MJ. The clinical significance of serrated polyps. Am J Gastroenterol 2011; 106:229-40; quiz 241. [PMID: 21045813 DOI: 10.1038/ajg.2010.429] [Citation(s) in RCA: 129] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is a heterogeneous disorder than arises via multiple distinct pathways, such as the serrated pathway, in which serrated polyps (including variants of hyperplastic polyps) are the precursor lesions. Approximately 15-20% of all CRCs arise via the serrated pathway, and these serrated carcinomas are clinically, morphologically, and molecularly distinct from conventional CRCs. The prevention of serrated carcinomas represents an important clinical challenge. Gastroenterologists need to recognize and remove potential precursor lesions and implement a post-polypectomy surveillance program when appropriate. This article focuses on the characteristics and significance of clinically relevant serrated polyps and addresses implications for CRC prevention practices.
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Affiliation(s)
- Christopher S Huang
- Department of Medicine, Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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44
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Balaguer F, Castells A. Hyperplastic Polyps: Are They Completely Innocent? CURRENT COLORECTAL CANCER REPORTS 2011. [DOI: 10.1007/s11888-010-0080-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Hiraoka S, Kato J, Fujiki S, Kaji E, Morikawa T, Murakami T, Nawa T, Kuriyama M, Uraoka T, Ohara N, Yamamoto K. The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology 2010; 139:1503-10, 1510.e1-3. [PMID: 20643134 DOI: 10.1053/j.gastro.2010.07.011] [Citation(s) in RCA: 164] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2010] [Revised: 07/01/2010] [Accepted: 07/07/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS There is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. METHODS We performed a multicenter observational study of 10,199 subjects who underwent first-time colonoscopies. Data collected on study subjects included age and sex and the location, size, and histology of polyps or tumors found at colonoscopy. Serrated polyps were defined as those diagnosed by the pathologists in the participating hospitals as a serrated lesion (a lesion given the term of "classical hyperplastic polyp," "traditional serrated adenoma," "sessile serrated adenoma," or "mixed serrated polyp"). Large serrated polyps (LSPs) were defined as those ≥ 10 mm. RESULTS There were 1573 patients (15.4%) with advanced neoplasia, 708 patients (6.9%) with colorectal cancer (CRC), and 140 patients (1.4%) with LSPs in our cohort. Multivariate analysis associated the presence of LSPs with advanced neoplasia (odds ratio [OR], 4.01; 95% confidence interval [CI], 2.83-5.69) and CRC (OR, 3.34; 95% CI, 2.16-5.03). The presence of LSPs was the greatest risk factor for CRC, particularly for proximal CRC (OR, 4.79; 95% CI, 2.54-8.42). Proximal and protruded LSPs were the highest risk factors for proximal CRC (OR, 5.36; 95% CI, 2.40-10.8 and OR, 9.00; 95% CI, 2.75-19.2, respectively). CONCLUSIONS The presence of LSPs is a risk factor for CRC, particularly CRC of the proximal colon.
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Affiliation(s)
- Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Buchanan DD, Roberts A, Walsh MD, Parry S, Young JP. Lessons from Lynch syndrome: a tumor biology-based approach to familial colorectal cancer. Future Oncol 2010; 6:539-49. [PMID: 20373868 DOI: 10.2217/fon.10.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancer (CRC) develops within precursor lesions in the single-celled epithelial lining of the gut. The two most common epithelial lesions are the adenoma and the serrated polyp. CRC is also one of the most familial of the common cancers, and just as there are syndromes associated with increased risk of CRC arising in adenomas, there are also syndromes with increased CRC risk associated with serrated polyps. In this article, we describe the features of such a syndrome, familial serrated neoplasia, which distinguish it from the well-characterized condition Lynch syndrome (or hereditary nonpolyposis CRC), and show that the molecular pathology of tumors forms the basis for this distinction. Lynch syndrome CRC arises almost exclusively within adenomatous precursor lesions, in contrast with familial serrated neoplasia where at least half of the cancers develop in serrated polyps. Finally, rare families exist in which both conditions segregate independently, producing a difficult diagnostic picture.
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Huppertz J, Coriat R, Leblanc S, Gaudric M, Brezault C, Grandjouan S, Chaput U, Prat F, Chaussade S. Application of ANAES guidelines for colonoscopy in France: a practical survey. ACTA ACUST UNITED AC 2010; 34:541-8. [PMID: 20739131 DOI: 10.1016/j.gcb.2010.03.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2009] [Revised: 02/22/2010] [Accepted: 03/07/2010] [Indexed: 01/09/2023]
Abstract
OBJECTIVES In 2004, the French health authorities published guidelines on the indications for colonoscopy. However, no study has evaluated the awareness of healthcare practitioners of these guidelines. The aim of this study was to determine the level of awareness of the ANAES guidelines among French gastroenterologists. PATIENTS AND METHODS A questionnaire comprising 20 multiple choice questions (MCQ) was presented to a group of 79 gastroenterologists between February and June in 2008. The questions covered screening tests for colon cancer (one question), endoscopic mucosal resection (two questions) and the ANAES guidelines (17 questions). According to the number of colonoscopies performed per year (less than 100, 100-500, more than 500), the answers to these questions were analyzed separately. RESULTS Among the practitioners carrying out less than 100, 100-500 and more than 500 colonoscopies per year, the guidelines for colon cancer screening were known by 33, 50 and 56%, respectively, the quality criteria for endoscopic mucosal resection by 0, 0 and 3.7%, respectively, and the ANAES guideline indications for colonoscopy by 34.3, 51.2 and 48.9%, respectively (P<0.001). The ANAES guidelines were significantly better known by practitioners who were performing more than 100 colonoscopies per year, while the indications for control colonoscopy were less often correctly anticipated. No differences were found concerning postponed indications. CONCLUSION The ANAES guidelines consists of the following elements: (1) awareness of the ANAES guidelines is poor, with control colonoscopy being correctly anticipated in just over a third of the gastroenterologists; (2) performing more than 100 colonoscopies per year improves knowledge of the ANAES guidelines; and (3) the ANAES guidelines need to be simplified and should be covered by continuing medical education.
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Affiliation(s)
- J Huppertz
- Service de gastroentérologie, CHU Cochin, faculté René-Descartes-Paris-V, 27 rue du Faubourg-Saint-Jacques, Paris, France
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Risio M. Reprint of: the natural history of adenomas. Best Pract Res Clin Gastroenterol 2010; 24:397-406. [PMID: 20833344 DOI: 10.1016/j.bpg.2010.08.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2010] [Revised: 04/13/2010] [Accepted: 04/13/2010] [Indexed: 01/31/2023]
Abstract
It is well known that adenomas represent the morphologically categorised precursor of the vast majority of colorectal cancers. Only few adenomas actually develop invasive cancer (progressive adenomas), although every adenoma has the capacity of malignant evolution. Most adenomas stabilise their progression or even regress. Easily identifiable but widely ranged pathological features (size, architectural growth, type, grade and gross organisation of dysplasia) are predictive of their natural history in terms of potential of cancerisation and duration of the adenoma-carcinoma sequence. Knowledge of the biological machineries sustaining the progression rates and times could be crucial to refine the natural history assumptions in screening modelling.
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Affiliation(s)
- Mauro Risio
- Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), Strada Provinciale 142, Km. 3,95, 10060 Candiolo, Torino, Italy.
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Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics. PLoS One 2010; 5:e11636. [PMID: 20661287 PMCID: PMC2905435 DOI: 10.1371/journal.pone.0011636] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2010] [Accepted: 06/15/2010] [Indexed: 12/15/2022] Open
Abstract
Background Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.
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Bujanda L, Cosme A, Gil I, Arenas-Mirave JI. Malignant colorectal polyps. World J Gastroenterol 2010; 16:3103-3111. [PMID: 20593495 PMCID: PMC2896747 DOI: 10.3748/wjg.v16.i25.3103] [Citation(s) in RCA: 118] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 04/07/2010] [Accepted: 04/14/2010] [Indexed: 02/06/2023] Open
Abstract
Nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (NHGN), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. NHGN is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic factors include, sessile or pedunculated morphology of the polyp, whether partial or en bloc resection is carried out, the degree of differentiation of the carcinoma, vascular or lymphatic involvement, and whether the polypectomy resection margin is tumor free. A malignant polyp at T1 is considered cured with polypectomy if it is a pedunculated polyp (Ip of the Paris classification), it has been completely resected, it is not poorly differentiated, the resection edge is not affected by the tumor and there is no vascular or lymphatic involvement. The sessile malignant polyp (Is of the Paris classification) at T1 is considered not cured with polypectomy. Only in some cases (e.g. older people with high surgical risk) local excision (polypectomy or endoscopic submucosal dissection or conventional endoscopic mucosal resection) is considered the definitive treatment.
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