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Toyoshima O, Nishizawa T, Yoshida S, Arano T, Watanabe H, Mizutani H, Yamada T, Takatori Y, Ebinuma H, Saito Y. Characteristics of Clinically Significant Hyperplastic Polyps: Distinctions Between Microvesicular and Goblet Cell-Rich Types. J Gastroenterol Hepatol 2025; 40:1182-1187. [PMID: 40025862 DOI: 10.1111/jgh.16921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/07/2025] [Accepted: 02/14/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Clinically significant serrated polyps (CSSPs) are defined as sessile serrated lesions (SSLs), SSLs with dysplasia, traditional serrated adenomas (TSAs), hyperplastic polyps (HPs) ≥ 10 mm, and HPs ≥ 6 mm in the proximal colon. HPs are further classified as microvesicular HPs (MVHPs) and goblet cell-rich HPs (GCHPs). Among CSSPs, HPs were categorized into clinically significant MVHPs (CS-MVHPs) and clinically significant GCHPs (CS-GCHPs). This study compares the characteristics of CS-MVHPs, CS-GCHPs, and SSLs. METHODS This study included patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic between March 2021 and April 2024. Lesions diagnosed as adenomas or CSSPs were removed. Age, sex, number of polyps, detection rate, and polyp size were compared among CS-MVHPs, CS-GCHPs, and SSLs. RESULTS In total, 14 065 patients were enrolled. The detection rates for CS-MVHPs, CS-GCHPs, and SSLs were 5.24%, 1.22%, and 6.36%, respectively. Patients with CS-MVHPs or SSLs were significantly younger and more often female than those with CS-GCHPs. The mean sizes of CS-MVHPs and SSLs were significantly larger than that of CS-GCHPs. The detection rate of CS-GCHPs increased with age, whereas the detection rates of CS-MVHPs and SSLs did not show a similar trend. CONCLUSIONS Compared with CS-GCHPs, CS-MVHPs were larger, more frequent, and more likely to be found in younger patients and females. The characteristics of CS-MVHPs are similar to those of SSLs, supporting the hypothesis that CS-MVHPs are precursors of SSLs.
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Affiliation(s)
| | - Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | | | - Toru Arano
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | | | - Hiroya Mizutani
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoharu Yamada
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yusaku Takatori
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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Fernandes-Mendes H, Azevedo CM, Garrido M, Lemos C, Pedroto I, Pinho SS, Marcos-Pinto R, Fernandes Â. Risk Factors in Serrated Pathway Lesions: N-Glycosylation Profile as a Potential Biomarker of Progression to Malignancy. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:338-350. [PMID: 39360170 PMCID: PMC11444659 DOI: 10.1159/000535920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 11/23/2023] [Indexed: 10/04/2024]
Abstract
Introduction The serrated pathway contributes to interval colorectal cancers, highlighting the need for new biomarkers to assess lesion progression risk. The β1,6-GlcNAc branched N-glycans expression in CRC cells was associated with an invasive phenotype and with immune evasion. Therefore, this study aims to identify potential risk factors for progression of serrated lesions (SLs) to malignancy, analyzing the N-glycosylation profile of epithelial/infiltrating immune cells. Methods A retrospective cohort study was performed with data from 53 colonoscopies (48 patients). Sixty-three serrated pathway lesions (SPLs) were characterized based on N-glycosylation profile (lectin histochemistry/flow cytometry) and MGAT5 expression. Statistical analysis was performed to search for associations between the glycoprofile and clinical variables from each patient. Results Increased β1,6-GlcNAc branched N-glycans expression in epithelial cells is found associated with age (p = 0.007 in SPL), smoking (p = 0.038 in SL), increased BMI (p = 0.036 in sessile serrated lesions [SSL]), and polyp dimensions ≥10 mm (p = 0.001 in SL), while increased expression of these structures on immune cells is associated with synchronous CA number (CD4+T cells: p = 0.016; CD8+T cells: p = 0.044 in SL) and female gender (p = 0.026 in SL). Moreover, a lower high-mannose N-glycans expression in immune cells is associated with smoking (p = 0.010 in SPL) and synchronous CA presence (p = 0.010 in SPL). Higher expression of these glycans is associated with female (p = 0.016 in SL) and male (p = 0.044 in SL) gender, left colon location (p = 0.028), dysplasia (p = 0.028), and adenocarcinoma (p = 0.010). Conclusions We identified an association between an abnormal glycoprofile and several clinical risk factors, proposing the N-glycosylation profile as a potential biomarker of tumor progression in the serrated pathway. The N-glycosylation anatomopathological profile analysis could be further used to decide shorter interval follow-up in patients with SPL.
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Affiliation(s)
- Henrique Fernandes-Mendes
- Department of Gastroenterology, Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Catarina M. Azevedo
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
| | - Mónica Garrido
- Department of Gastroenterology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Carolina Lemos
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
| | - Isabel Pedroto
- Department of Gastroenterology, Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Salomé S. Pinho
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
| | - Ricardo Marcos-Pinto
- Department of Gastroenterology, Centro Hospitalar Universitário de Santo António, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal
| | - Ângela Fernandes
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
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Yan L, Shi J, Zhu J. Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions. Discov Oncol 2024; 15:294. [PMID: 39031216 PMCID: PMC11265098 DOI: 10.1007/s12672-024-01163-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/15/2024] [Indexed: 07/22/2024] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.
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Affiliation(s)
- Lei Yan
- Medical Department, The Central Hospital of Shaoyang Affiliated to University of South China, Shaoyang, China
| | - Jia Shi
- Department of Obstetrics and Gynecology, The Central Hospital of Shaoyang Affiliated to University of South China, Shaoyang, China
| | - Jiazuo Zhu
- Department of Oncology, Xuancheng City Central Hospital, No. 117 Tong Road, Xuancheng, Anhui, China.
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Sutherland RL, Boyne DJ, Brenner DR, Cheung WY. The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada. Cancers (Basel) 2023; 15:5748. [PMID: 38136294 PMCID: PMC10741517 DOI: 10.3390/cancers15245748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/27/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan-Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis.
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Affiliation(s)
- R. Liam Sutherland
- Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Devon J. Boyne
- Department of Oncology, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Darren R. Brenner
- Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 4N1, Canada
- Department of Oncology, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Winson Y. Cheung
- Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 4N1, Canada
- Department of Oncology, University of Calgary, Calgary, AB T2N 4N1, Canada
- Department of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
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Boylan KE, Kanth P, Delker D, Hazel MW, Boucher KM, Affolter K, Clayton F, Evason KJ, Jedrzkiewicz J, Pletneva M, Samowitz W, Swanson E, Bronner MP. Three pathologic criteria for reproducible diagnosis of colonic sessile serrated lesion versus hyperplastic polyp. Hum Pathol 2023; 137:25-35. [PMID: 37044202 PMCID: PMC10330587 DOI: 10.1016/j.humpath.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/05/2023] [Accepted: 04/06/2023] [Indexed: 04/14/2023]
Abstract
Colonic SSLs are thought to predispose to ∼30% of colonic adenocarcinomas. This increased risk, compared to benign HPs, makes their distinction vitally important. However, no gold standard exists to differentiate them, and wide observer variability is reported. To better distinguish these polyps, we investigated 94 serrated polyps (53 SSLs and 41 HPs) using an easy-to-apply pathologic scoring system that combines, for the first time, three established distinguishing features: polyp morphology, location, and size. As an additional novel approach, polyp size was assessed by serrated biopsy number compared to endoscopic size. RNA expression profiling served as an additional biomarker. The considerable morphologic overlap across serrated polyps was quantitated for the first time. Interobserver variability was assessed by 8 expert gastrointestinal pathologists. By ROC analysis, polyp size by biopsy number performed best, followed by polyp location and morphology (areas under the curves [AUCs] = 85.9%, 81.2%, and 65.9%, respectively). Optimal discrimination combined all 3 features (AUC = 92.9%). For polyp size, the biopsy number proved superior to endoscopic size (AUC = 85.9% versus 55.2%, P = .001). Interobserver variability analysis yielded the highest reported Fleiss and Kappa statistics (0.879) and percent agreement (96.8%), showing great promise toward improved diagnosis. The proposed 3-criteria pathologic system, combining size by biopsy number, location, and morphology, yields an improved, easy-to-use, and highly reproducible diagnostic approach for differentiating SSLs and HPs.
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Affiliation(s)
| | | | - Don Delker
- Division of Gastroenterology, 84112, USA
| | | | - Kenneth M Boucher
- Division of Epidemiology, University of Utah, Salt Lake City, UT, 84112, USA
| | - Kajsa Affolter
- Department of Pathology and ARUP Laboratories, 84112, USA
| | - Fred Clayton
- Department of Pathology and ARUP Laboratories, 84112, USA
| | | | | | - Maria Pletneva
- Department of Pathology and ARUP Laboratories, 84112, USA
| | - Wade Samowitz
- Department of Pathology and ARUP Laboratories, 84112, USA
| | - Eric Swanson
- Department of Pathology and ARUP Laboratories, 84112, USA
| | - Mary P Bronner
- Department of Pathology and ARUP Laboratories, 84112, USA
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Vithayathil M, Smith S, Song M. Epidemiology of overall and early-onset serrated polyps versus conventional adenomas in a colonoscopy screening cohort. Int J Cancer 2023; 152:1085-1094. [PMID: 36178673 DOI: 10.1002/ijc.34306] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/12/2022] [Accepted: 09/23/2022] [Indexed: 01/21/2023]
Abstract
Serrated polyps (SPs) are precursors to one-third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early-onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy-based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early-onset polyps. Ninety-four thousand four hundred and twenty-seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High-risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high-grade dysplasia. We examined polyp prevalence with age and compared early- (age < 50) and late-onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty-five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High-risk SSLs were enriched in the ascending colon (44.1% vs 2.6-35.8% for other locations; P < .003). Early- and late-onset SPs had similar subsite distribution. Early-onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P < .001). Multiple conventional adenomas were more represented in late-onset groups (40.8% vs 33.8%, P < .001), with no difference in SSLs. The prevalence of conventional adenomas/high-risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high-risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early-onset than late-onset SSLs (62.9% vs 57.6%, P = .03). Conventional adenomas, SSLs, early- and late-onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC.
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Affiliation(s)
- Mathew Vithayathil
- Department of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Scott Smith
- Department of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Mingyang Song
- Department of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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O'Sullivan DE, Ruan Y, Forbes N, Heitman SJ, Hilsden RJ, Pader J, Brenner DR. Long-term Use of Hormone Replacement Therapy is Associated With a Lower Risk of Developing High-risk Serrated Polyps in Women. J Clin Gastroenterol 2022; 56:697-704. [PMID: 34406174 DOI: 10.1097/mcg.0000000000001606] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/20/2021] [Indexed: 01/25/2023]
Abstract
GOALS/BACKGROUND Hormone replacement therapy (HRT) and parity have been suggested protective factors against the development of colorectal polyps. However, there are a limited number of studies that have examined the relationship of these factors with high-risk adenomatous polyps (HRAP) or high-risk serrated polyps (HRSP), which may have different causes and therefore implications for screening programs. STUDY Data from a cross-sectional study of 1384 women undergoing screening-related colonoscopy between 2008 and 2016 were analyzed. Modified Poisson regression models with robust error variance were used to determine the relative risk of developing adenomatous polyps, serrated polyps, HRAPs, and HRSPs associated with pregnancy, menopausal status, and the use of HRT (duration and type). RESULTS Women that used HRT for ≥6 years were at a significantly lower risk of developing a HRSP [risk ratios (RR): 0.53; 95% confidence interval (CI): 0.29-0.97]. Irrespective of the duration of use, the use of HRT that included progesterone alone or with estrogen was associated with a significantly lower risk of developing a HRSP (RR: 0.54; 95% CI: 0.30-0.95). The use HRT with progesterone for ≥6 years was associated with a nonsignificant lower risk of developing a HRSP (RR: 0.42; 95% CI: 0.17-1.04). None of the reproductive factors assessed or HRT were associated with the development of adenomatous polyps or HRAPs. CONCLUSIONS The results of this study suggests that the long-term use of HRT, and therapies that include progesterone are associated with a lower risk of developing HRSPs. These results could have implications for targeted screening for serrated polyps among women.
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Affiliation(s)
- Dylan E O'Sullivan
- Departments of Community Health Sciences
- Oncology
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada
| | - Yibing Ruan
- Department of Cancer Epidemiology and Prevention Research, Alberta Health Services
| | - Nauzer Forbes
- Departments of Community Health Sciences
- Medicine, Cumming School of Medicine, University of Calgary
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada
| | - Steven J Heitman
- Departments of Community Health Sciences
- Medicine, Cumming School of Medicine, University of Calgary
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada
| | - Robert J Hilsden
- Departments of Community Health Sciences
- Medicine, Cumming School of Medicine, University of Calgary
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada
| | - Joy Pader
- Department of Cancer Epidemiology and Prevention Research, Alberta Health Services
| | - Darren R Brenner
- Departments of Community Health Sciences
- Oncology
- Department of Cancer Epidemiology and Prevention Research, Alberta Health Services
- Forzani and MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB, Canada
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Crockett SD, Barry EL, Mott LA, Snover DC, Wallace K, Baron JA. Predictors of Incident Serrated Polyps: Results from a Large Multicenter Clinical Trial. Cancer Epidemiol Biomarkers Prev 2022; 31:1058-1067. [PMID: 35506244 DOI: 10.1158/1055-9965.epi-21-1226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/07/2022] [Accepted: 02/16/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Serrated polyps (SP) are important colorectal cancer precursors, yet their epidemiology is incompletely understood. We measured risk factors for incident sessile-serrated lesions (SSL) and microvesicular (MVHP) and goblet-cell rich (GCHP) hyperplastic polyp subtypes. METHODS We conducted a cohort study of patients undergoing colonoscopic surveillance nested within a chemoprevention trial. Outcomes of interest were ≥1 SPs, including SSLs, MVHPs, and GCHPs specifically. Multivariable generalized estimating equation models were used to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for different polyp types. RESULTS Among 2,102 participants, a total of 1,615 SPs (including 212 SSLs) were found among 758 participants during follow-up. Prior history of SPs was strongly associated with subsequent occurrence of SPs. There was no apparent association between age, sex, or education and risk of SPs. Black participants were at lower risk of SSLs and MVHPs, but higher risk of GCHPs compared with white participants [RR, 0.40; 95% CI, 0.16-0.99); RR, 0.63 (95% CI, 0.42-0.96); and RR, 1.83 (95% CI, 1.23-2.72) respectively]. Alcohol and smoking exposure were also associated with SPs, including hyperplastic polyp subtypes in particular. CONCLUSIONS In this prospective study, the risk of SP subtypes differed by race, alcohol, and smoking status, and prior history of SPs. Risk factor associations for SPs differ from risk factors for conventional adenomas, supporting the concept of etiologic heterogeneity of colorectal cancer. IMPACT These findings allow for better risk stratification of patients undergoing colorectal cancer screening and could inform screening test selection.
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Affiliation(s)
- Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Elizabeth L Barry
- Department of Epidemiology, Geisel Dartmouth School of Medicine, Lebanon, New Hampshire
| | - Leila A Mott
- Department of Epidemiology, Geisel Dartmouth School of Medicine, Lebanon, New Hampshire
| | - Dale C Snover
- University of Minnesota (Retired), Minneapolis, Minnesota
| | - Kristin Wallace
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
| | - John A Baron
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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Papastergiou V, Viazis N, Mantzaris GJ. Letter: towards gender-stratified colorectal cancer screening and surveillance? Aliment Pharmacol Ther 2022; 55:504-505. [PMID: 35092048 DOI: 10.1111/apt.16737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Vasilios Papastergiou
- Gastroenterology Department, Evangelismos-Polykliniki General Hospitals of Athens, Athens, Greece
| | - Nikos Viazis
- Gastroenterology Department, Evangelismos-Polykliniki General Hospitals of Athens, Athens, Greece
| | - Gerassimos J Mantzaris
- Gastroenterology Department, Evangelismos-Polykliniki General Hospitals of Athens, Athens, Greece
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Lall V, Ismail AGM, Ayonrinde OT. Disparate age and sex distribution of sessile serrated lesions and conventional adenomas in an outpatient colonoscopy population-implications for colorectal cancer screening? Int J Colorectal Dis 2022; 37:1569-1579. [PMID: 35660947 PMCID: PMC9262786 DOI: 10.1007/s00384-022-04191-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/21/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE Colorectal cancer (CRC) is increasingly diagnosed in individuals aged < 50 years, resulting in advocacy of screening from age 45 years. Despite existing knowledge associating CRC with conventional adenomas, the significance of sessile serrated lesions (SSLs) on the burden of CRC is less detailed. We aimed to provide contemporary estimates for SSL prevalence and examine patient and procedure factors associated with SSL detection. METHODS Retrospective observational study examining associations between SSL and conventional adenoma detection, polyp histopathology, patient, and procedure characteristics in an outpatient colonoscopy unit over 12 months. RESULTS From 2097 colonoscopies, SSL detection was 13.8% overall and 12.5% in patients < 50 years. SSLs were mostly proximal in location (64%), and SSL detection was significantly higher in females compared with males (16.2% vs. 11.7%, p = 0.003), particularly in those < 50 years (16.8% vs. 8.6%, p < 0.001). In multivariable analysis, SSL detection was associated with female sex (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.15-1.91), synchronous conventional adenoma detection (aOR 1.36, 95% CI 1.04-1.78) and BMI ≥ 25 kg/m2 (aOR 1.34, 95% CI 1.02-1.77). Conventional adenoma detection was 33.6% and associated with age ≥ 50 years (aOR 3.57, 95% CI 2.84-4.47) and synchronous SSL detection (aOR 1.36, 95% CI 1.03-1.79). CONCLUSIONS We observed age and sex disparities in polyp types and prevalence in this outpatient colonoscopy population. SSLs were most prevalent in females aged < 50 years, suggesting a potential increased susceptibility of young females to SSLs and CRC. Our findings may have implications for the design of CRC screening programs.
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Affiliation(s)
- Vidit Lall
- Sir Charles Gairdner Hospital, Nedlands, Australia ,Medical School, The University of Western Australia, Nedlands, Australia
| | - Ali Galalah Mostafa Ismail
- Royal Perth Hospital, Perth, Australia ,Medical School, The University of Western Australia, Nedlands, Australia
| | - Oyekoya Taiwo Ayonrinde
- Medical School, The University of Western Australia, Nedlands, Australia ,Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, Australia ,Faculty of Health Sciences, Curtin University, Bentley, Australia
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Heckroth M, Eiswerth M, Elmasry M, Gala K, Cai W, Diamond S, Shine A, Liu D, Liu N, Tholkage S, Kong M, Parajuli D. Serrated polyp detection rate in colonoscopies performed by gastrointestinal fellows. Ther Adv Gastrointest Endosc 2022; 15:26317745221136775. [PMCID: PMC9749503 DOI: 10.1177/26317745221136775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 10/17/2022] [Indexed: 12/15/2022] Open
Abstract
Background: Clinically significant serrated polyp detection rate (CSSDR) and proximal serrated polyp detection rate (PSDR) have been suggested as the potential quality benchmarks for colonoscopy (CSSDR = 7% and PSDR = 11%) in comparison to the established benchmark adenoma detection rate (ADR). Another emerging milestone is the detection rate of lateral spreading lesions (LSLs). Objectives: This study aimed to evaluate CSSDR, PSDR, ADR, and LSL detection rates among gastrointestinal (GI) fellows performing a colonoscopy. A secondary aim was to evaluate patient factors associated with the detection rates of these lesions. Design and Methods: A retrospective review of 799 colonoscopy reports was performed. GI fellow details, demographic data, and pathology found on colonoscopy were collected. Multiple logistic regression analysis was performed to identify the factors associated with CSSDR, PSDR, ADR, and LSL detection rates. A p value < 0.05 was considered statistically significant. Results: For our patient population, the median age was 58 years; 396 (49.8%) were male and 386 (48.6%) were African American. The 15 GI fellows ranged from first (F1), second (F2), or third (F3) year of training. We found an overall CSSDR of 4.4%, PSDR of 10.5%, ADR of 42.1%, and LSL detection rate of 3.2%. Female gender was associated with CSSDR, while only age was associated with PSDR. GI fellow level of training was associated with LSL detection rate, with the odds of detecting them expected to be four times higher in F2/F3s than F1s. Conclusion: Although GI fellows demonstrated an above-recommended ADR and nearly reached target PSDR, they failed to achieve target CSSDR. Future studies investigating a benchmark for LSL detection rate are needed to quantify if GI fellows are detecting these lesions at adequate rates.
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Affiliation(s)
- Matthew Heckroth
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Michael Eiswerth
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Mohamed Elmasry
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Khushboo Gala
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Wenjing Cai
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Scott Diamond
- Department of Internal Medicine, University of Louisville, Louisville, KY, USA
| | - Amal Shine
- Department of Gastroenterology and Hepatology, University of Louisville, Louisville, KY, USA
| | - David Liu
- School of Medicine, University of Louisville, Louisville, KY, USA
| | - Nanlong Liu
- Department of Gastroenterology and Hepatology, University of Louisville, Louisville, KY, USA
| | - Sudaraka Tholkage
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA
| | - Maiying Kong
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA
| | - Dipendra Parajuli
- Department of Gastroenterology and Hepatology, University of Louisville, 550 S Jackson St, Louisville, KY 40202, USA
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Chavda V, Siaw O, Chaudhri S, Runau F. Management of early rectal cancer; current surgical options and future direction. World J Gastrointest Surg 2021; 13:655-667. [PMID: 34354799 PMCID: PMC8316852 DOI: 10.4240/wjgs.v13.i7.655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/13/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Rectal cancer is the second commonest cause of cancer death within the United Kingdom. Utilization of national screening programmes have resulted in a greater proportion of patients presenting with early-stage disease. The technique of transanal endoscopic microsurgery was first described in 1984 following which further options for local excision have emerged with transanal endoscopic operation and, more recently, transanal minimally invasive surgery. Owing to the risks of local recurrence, the current role of minimally invasive techniques for local excision in the management of rectal cancer is limited to the treatment of pre-invasive disease and low risk early-stage rectal cancer (T1N0M0 disease). The roles of chemotherapy and radiotherapy for the management of early rectal cancer are yet to be fully established. However, results of high-quality research such as the GRECCAR II, TESAR and STAR-TREC randomised control trials may highlight a wider role for local excision surgery in the future, when used in combination with oncological therapies. The aim of our review is to provide an overview in the current management of early rectal cancer, the surgical options available for local excision and the future multimodal direction of early rectal cancer treatment.
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Affiliation(s)
- Vijay Chavda
- Department of General Surgery, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Oliver Siaw
- Department of General Surgery, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Sanjay Chaudhri
- Department of General Surgery, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
| | - Franscois Runau
- Department of General Surgery, Leicester General Hospital, Leicester LE5 4PW, United Kingdom
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13
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Ebner DW, Eckmann JD, Burger KN, Mahoney DW, Bering J, Kahn A, Rodriguez EA, Prichard DO, Wallace MB, Kane SV, Finney Rutten LJ, Gurudu SR, Kisiel JB. Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA. Clin Transl Gastroenterol 2021; 12:e00375. [PMID: 34140458 PMCID: PMC8216679 DOI: 10.14309/ctg.0000000000000375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/20/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.
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Affiliation(s)
- Derek W. Ebner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jason D. Eckmann
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kelli N. Burger
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Douglas W. Mahoney
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Jamie Bering
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Allon Kahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Eduardo A. Rodriguez
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - David O. Prichard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic Health System, La Crosse, Wisconsin, USA
| | - Michael B. Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Sunanda V. Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Suryakanth R. Gurudu
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - John B. Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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14
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Sacco M, De Palma FDE, Guadagno E, Giglio MC, Peltrini R, Marra E, Manfreda A, Amendola A, Cassese G, Dinuzzi VP, Pegoraro F, Tropeano FP, Luglio G, De Palma GD. Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways. Open Med (Wars) 2020; 15:1087-1095. [PMID: 33336065 PMCID: PMC7718641 DOI: 10.1515/med-2020-0226] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 07/14/2020] [Accepted: 08/07/2020] [Indexed: 12/26/2022] Open
Abstract
In 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70-90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10-20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts' opinions.
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Affiliation(s)
- Michele Sacco
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Fatima Domenica Elisa De Palma
- CEINGE Biotecnologie Avanzate s.c.ar.l., Via Comunale Margherita, 80131, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Elia Guadagno
- Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy
| | - Mariano Cesare Giglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Roberto Peltrini
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Ester Marra
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Andrea Manfreda
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Alfonso Amendola
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Gianluca Cassese
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Vincenza Paola Dinuzzi
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Francesca Pegoraro
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Francesca Paola Tropeano
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Gaetano Luglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
| | - Giovanni Domenico De Palma
- Department of Clinical Medicine and Surgery, University of Naples Federico II via Sergio Pansini, 5 – 80131, Naples, Italy
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15
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Chang MC, Ma CC, Yu HC, Hsu PI, Liao JB, Huang CC. Detection and clinical characteristics of serrated polyps and conventional adenomas between patients in the outpatient and physical checkup unit receiving colonoscopy. Int J Colorectal Dis 2020; 35:1979-1987. [PMID: 32556459 DOI: 10.1007/s00384-020-03665-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE The sessile serrated adenoma/polyp detection rate (SSA/PDR) among different colonoscopy indications from daily practice has not been fully understood. This study aimed to evaluate the detection and clinical characteristics of serrated polyps and conventional adenomas between outpatient department (OPD) and physical checkup unit (PCU) patients receiving colonoscopy. METHODS The data for this retrospective study were collected between 2016 and 2017 at Kaohsiung Veterans General Hospital in Taiwan. A total of 7047 individuals were included, and information on polyp and adenoma detection was extracted from the colonoscopy reports. RESULTS The adenoma detection rate, the SSA/PDR, and the detection rate of traditional serrated adenoma (TSA) were 32.2%, 0.60%, and 0.50%, respectively. Risk analysis revealed no significant difference (p = 0.095) in SSA/PDR between individuals < 50 years and ≥ 50 years, and no trend of increased SSA/PDR as age increased was observed (p = 0.320). SSA/P and TSA had higher risks for synchronous advanced neoplasia than conventional adenoma, but with proximal hyperplastic polyps lower (p < 0.001, respectively). No significant difference of SSA/PDR between OPD and PCU patients was observed (p = 1.000); however, the age of SSA/P was significantly older in OPD than in PCU patients (p = 0.048). CONCLUSION The detection rates of CA and TSA were associated with age groups; however, SSA/PDR was insignificantly higher among individuals aged < 50 years than those with other age groups. In addition, SSA/PDR between OPD and PCU patients was not significantly found in daily practice of colonoscopies.
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Affiliation(s)
- Min-Chi Chang
- Division of Colorectal Surgery, Surgical Department, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Health Business Administration, Meiho University, Pingtung, Taiwan
| | - Chen-Chung Ma
- Department of Healthcare Administration, I-Shou University, Kaohsiung City, Taiwan
| | - Hsien-Chung Yu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Department of Medicine, Tainan Municipal An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Jia-Bin Liao
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
- College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chun-Che Huang
- Department of Healthcare Administration, I-Shou University, Kaohsiung City, Taiwan.
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16
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Bozorg SR, Song M, Emilsson L, Ludvigsson JF. Validation of serrated polyps (SPs) in Swedish pathology registers. BMC Gastroenterol 2019; 20:3. [PMID: 31892305 PMCID: PMC6938642 DOI: 10.1186/s12876-019-1134-6] [Citation(s) in RCA: 5] [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: 05/05/2019] [Accepted: 12/04/2019] [Indexed: 12/18/2022] Open
Abstract
Background Little is known about the natural history of serrated polyps (SPs), partly due to the lack of large-scale epidemiologic data. In this study, we examined the validity of SP identification according to SNOMED (Systematised Nomenclature of Medicine) codes and free text from colorectal histopathology reports. Methods Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, we retrieved data on SPs from all pathology departments in Sweden in 2015–2017 by using SNOMED codes and free-text search in colorectal histopathology reports. Randomly selected individuals with a histopathology report of SPs were validated against patient charts using a structured, retrospective review. Results SPs were confirmed in 101/106 individuals with a histopathology report of SPs, yielding a positive predictive value (PPV) of 95% (95%CI = 89–98%). By year of diagnosis, the PPV was 89% (95%CI = 69–97%), 96% (95%CI = 81–99%) and 97% (95%CI = 89–99%) for individuals diagnosed before 2001 (n = 19), between 2001 and 2010 (n = 26) and after 2010 (n = 61), respectively. According to search method, the PPV for individuals identified by SNOMED codes was 100% (95%CI = 93–100%), and 93% (95%CI = 86–97%) using free-text search. Recorded location (colon vs. rectum) was correct in 94% of all SP histopathology reports (95%CI = 84–98%) identified by SNOMED codes. Individuals with SPs were classified into hyperplastic polyps (n = 34; 32%), traditional serrated adenomas (n = 3; 3%), sessile serrated adenomas/polyps (SSA/Ps) (n = 70; 66%), unspecified SPs (n = 3, 3%), and false positive SPs (n = 5, 5%). For individuals identified by SNOMED codes, SSA/Ps were confirmed in 49/52 individuals, resulting in a PPV of 94% (95%CI: 84–98%). In total, 57% had ≥2 polyps (1: n = 44, 2–3: n = 33 and ≥ 4: n = 27). Some 46% of SPs (n = 71) originated from the proximal colon and 24% were ≥ 10 mm in size (n = 37). Heredity for colorectal cancer, intestinal polyposis syndromes, or both was reported in seven individuals (7%). Common comorbidities included diverticulosis (n = 45, 42%), colorectal cancer (n = 19, 18%), and inflammatory bowel disease (n = 10, 9%). Conclusion Colorectal histopathology reports are a reliable data source to identify individuals with SPs.
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Affiliation(s)
- Soran R Bozorg
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77, Solna, Sweden.
| | - Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Louise Emilsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77, Solna, Sweden.,Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Institute of Health and Society, University of Oslo, Oslo, Norway.,Vårdcentralen Värmlands Nysäter and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77, Solna, Sweden.,Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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He Z, Chen L, Chen G, Smaldini P, Bongers G, Catalan-Dibene J, Furtado GC, Lira SA. Interleukin 1 beta and Matrix Metallopeptidase 3 Contribute to Development of Epidermal Growth Factor Receptor-Dependent Serrated Polyps in Mouse Cecum. Gastroenterology 2019; 157:1572-1583.e8. [PMID: 31470007 PMCID: PMC7006742 DOI: 10.1053/j.gastro.2019.08.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 08/02/2019] [Accepted: 08/21/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Transgenic mice (HBUS) that express the epidermal growth factor receptor (EGFR) ligand HBEGF (heparin-binding epidermal growth factor-like growth factor) and a constitutively active G protein-coupled receptor (US28) in intestinal epithelial cells develop serrated polyps in the cecum. Development of serrated polyps depends on the composition of the gut microbiota and is associated with bacterial invasion of the lamina propria, accompanied by induction of inflammation and up-regulation of interleukin 1 beta (IL1B) and matrix metalloproteinase (MMP) 3 in the cecum. We investigated the mechanisms by which these changes contribute to development of serrated polyps. METHODS We performed studies with C57BL/6 (control) and HBUS mice. To accelerate polyp development, we increased the exposure of the bacteria to the lamina propria by injecting HBUS mice with diphtheria toxin, which binds transgenic HBEGF expressed by the epithelial cells and causes apoptosis. Mice were given injections of IL1B-neutralizing antibody and the MMP inhibitor N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid. Intestinal tissues were collected from mice and analyzed by histology, reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and flow cytometry. We examined fibroblast subsets in polyps using single-cell RNA sequencing. RESULTS Administration of diphtheria toxin to HBUS mice accelerated development of serrated polyps (95% of treated mice developed polyps before 100 days of age, compared with 53% given vehicle). IL1B stimulated subsets of platelet-derived growth factor receptor alpha+ (PDGRFA+) fibroblasts isolated from cecum, resulting in increased expression of MMP3. Neutralizing antibodies against IL1B or administration of the MMP inhibitor reduced the number of serrated polyps that formed in the HBUS mice. Single-cell RNA sequencing analysis showed subsets of fibroblasts in serrated polyps that express genes that regulate matrix fibroblasts and inflammation. CONCLUSIONS In studies of mice, we found that barrier breakdown and expression of inflammatory factors contribute to development of serrated polyps. Subsets of cecal PDGFRA+ fibroblasts are activated by release of IL1B from myeloid cells during the early stages of serrated polyp development. MMP3 produced by PDGFRA+ fibroblasts is important for serrated polyp development. Our findings confirm the functions of previously identified serrated polyp-associated molecules and indicate roles for immune and stromal cells in serrated polyp development.
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Affiliation(s)
- Zhengxiang He
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Lili Chen
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Grace Chen
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Paola Smaldini
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Gerold Bongers
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jovani Catalan-Dibene
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Glaucia C. Furtado
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Sergio A. Lira
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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18
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Kim J, Lee JY, Hwang SW, Park SH, Yang DH, Ye BD, Myung SJ, Yang SK, Koo JE, Lee HJ, Choe J, Byeon JS. Risk factors of traditional serrated adenoma and clinicopathologic characteristics of synchronous conventional adenoma. Gastrointest Endosc 2019; 90:636-646.e9. [PMID: 31063737 DOI: 10.1016/j.gie.2019.04.241] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 04/21/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Traditional serrated adenoma (TSA) is rare and known to have a malignant potential. We aimed to investigate the prevalence and risk factors of TSA and compare the characteristics of synchronous conventional adenoma (AD) in patients with TSA with those of AD in patients with AD only. METHODS We reviewed medical records of 31,932 healthy subjects who underwent screening colonoscopy at a single hospital between 2012 and 2017. RESULTS TSA was observed in 116 patients (.4%). Among them, 47 patients (40.5%) had TSA only and 69 patients (59.5%) had synchronous AD. Multivariable analysis showed independent risk factors for TSA to include age ≥50 years (odds ratio [OR], 3.34; 95% confidence interval [CI], 1.72-6.49; P < .001), hypertension (OR, 2.07; 95% CI, 1.09-3.92; P = .026), and current smoking (OR, 2.58; 95% CI, 1.28-5.23; P = .008). There were significantly more ADs (2.5 ± 2.0 vs 1.8 ± 1.6, P = .009) and ADs were of larger size (6.7 ± 5.0 vs 5.3 ± 3.6 mm, P = .027) in TSA patients than in AD-only patients. Furthermore, advanced adenoma and high-risk adenoma were more frequently observed in TSA patients than in AD-only patients (24.2% vs 11.2%, P = .002; 43.5% vs 23.6%, P < .001). CONCLUSIONS The prevalence of TSA in healthy adults was .4%. Age ≥50 years, hypertension, and current smoking may be risk factors of TSA. Synchronous AD is often observed with TSA and may show more advanced features than those in AD-only patients.
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Affiliation(s)
- Jeongseok Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ji Young Lee
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ja Eun Koo
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hyo Jeong Lee
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jaewon Choe
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Zimmermann-Fraedrich K, Sehner S, Rex DK, Kaltenbach T, Soetikno R, Wallace M, Leung WK, Guo C, Gralnek IM, Brand EC, Groth S, Schachschal G, Ikematsu H, Siersema PD, Rösch T. Right-Sided Location Not Associated With Missed Colorectal Adenomas in an Individual-Level Reanalysis of Tandem Colonoscopy Studies. Gastroenterology 2019; 157:660-671.e2. [PMID: 31103625 DOI: 10.1053/j.gastro.2019.05.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 05/07/2019] [Accepted: 05/10/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Interval cancers occur more frequently in the right colon. One reason could be that right-sided adenomas are frequently missed in colonoscopy examinations. We reanalyzed data from tandem colonoscopies to assess adenoma miss rates in relation to location and other factors. METHODS We pooled data from 8 randomized tandem trials comprising 2218 patients who had diagnostic or screening colonoscopies (adenomas detected in 49.8% of patients). We performed a mixed-effects logistic regression with patients as cluster effects with different independent parameters. Factors analyzed included location (left vs right, splenic flexure as cutoff), adenoma size, form, and histologic features. Analyses were controlled for potential confounding factors such as patient sex and age, colonoscopy indication, and bowel cleanliness. RESULTS Right-side location was not an independent risk factor for missed adenomas (odds ratio [OR] compared with the left side, 0.94; 95% CI, 0.75-1.17). However, compared with adenomas ≤5 mm, the OR for missing adenomas of 6-9 mm was 0.62 (95% CI, 0.44-0.87), and the OR for missing adenomas of ≥10 mm was 0.51 (95% CI, 0.33-0.77). Compared with pedunculated adenomas, sessile (OR, 1.82; 95% CI, 1.16-2.85) and flat adenomas (OR, 2.47; 95% CI, 1.49-4.10) were more likely to be missed. Histologic features were not significant risk factors for missed adenomas (OR for adenomas with high-grade intraepithelial neoplasia, 0.68; 95% CI, 0.34-1.37 and OR for sessile serrated adenomas, 0.87; 95% CI, 0.47-1.64 compared with low-grade adenomas). Men had a higher number of adenomas per colonoscopy (1.27; 95% CI, 1.21-1.33) than women (0.86; 95% CI, 0.80-0.93). Men were less likely to have missed adenomas than women (OR for missed adenomas in men, 0.73; 95% CI, 0.57-0.94). CONCLUSIONS In an analysis of data from 8 randomized trials, we found that right-side location of an adenoma does not increase its odds for being missed during colonoscopy but that adenoma size and histologic features do increase risk. Further studies are needed to determine why adenomas are more frequently missed during colonoscopies in women than men.
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Affiliation(s)
| | - Susanne Sehner
- Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Douglas K Rex
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Tonya Kaltenbach
- Veterans Administration San Francisco and University of California San Francisco, San Francisco, California
| | - Roy Soetikno
- Veterans Administration San Francisco and University of California San Francisco, San Francisco, California
| | - Michael Wallace
- Division of and Hepatology, Mayo Clinic Jacksonville, Jacksonville, Florida
| | - Wai K Leung
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
| | - Chuanguo Guo
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
| | - Ian M Gralnek
- Institute of Gastroenterology and Hepatology, Emek Medical Center, Afula, Israel
| | - Eelco C Brand
- Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands
| | - Stefan Groth
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Schachschal
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Hiroaki Ikematsu
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
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20
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Rezasoltani S, Khatibi S, Pezeshkiyan Z, Nazemalhosseini-Mojarad E, Sharafkhah M, Sadeghi A, Asadzadeh Aghdaei H, Zali MR. Investigating the TLR9 mRNA Expression Level in Different Histological Types of Colorectal Polyps. Asian Pac J Cancer Prev 2019; 20:2299-2302. [PMID: 31450898 PMCID: PMC6852833 DOI: 10.31557/apjcp.2019.20.8.2299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Indexed: 01/14/2023] Open
Abstract
Toll-like receptor 9 (TLR9) is a cellular DNA receptor of the innate immune system which plays a pivotal role in inflammatory response. Recently, changing expression levels of TLR9 has been observed in a wide range of cancer cells; however, there is little information about colorectal polyps. Herein, we assessed the mRNA expression of TLR9 in different colorectal polyp types compared to normal group in order to investigate its expression level during CRC initiation. Fifty-four biopsy samples from colorectal polyp patients and from 20 healthy subjects were collected. The mucosal mRNA expression level of TLR9 gene was identified by real time PCR. Fold change of gene expression was evaluated by 2-ΔΔct method. There was a significant relationship between the lower expression of TLR9 gene in the polyp cases compared to normal individuals (P value = 0.0005), Also, decreased TLR9 mRNA expression was obtained in adenomas in contrast to hyperplastic and normal groups (P value = 0.0008). Based on the current results, we hypothesized that aberrant surface expression of TLR9 on tumor cells may promote the growth and invasion of colorectal polyps. Further, TLR9 modulation may have an important impact on the development of novel therapeutic strategies.
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Affiliation(s)
- Sama Rezasoltani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Khatibi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Pezeshkiyan
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Sharafkhah
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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21
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The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer. Cancers (Basel) 2019; 11:cancers11071017. [PMID: 31330830 PMCID: PMC6678087 DOI: 10.3390/cancers11071017] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/15/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional serrated adenomas/polyps. Serrated polyps are characterized by genetic (BRAF or KRAS mutations) and epigenetic (CpG island methylator phenotype (CIMP)) alterations that cooperate to initiate and drive malignant transformation from normal colon mucosa to polyps, and then to CRC. The high heterogeneity of the serrated lesions renders their diagnostic and pathological interpretation difficult. Hence, novel genetic and epigenetic biomarkers are required for better classification and management of CRCs. To date, several molecular alterations have been associated with the serrated polyp-CRC sequence. In addition, the gut microbiota is emerging as a contributor to/modulator of the serrated pathway. This review summarizes the state of the art of the genetic, epigenetic and microbiota signatures associated with serrated CRCs, together with their clinical implications.
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22
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Pickhardt PJ, Pooler BD, Matkowskyj KA, Kim DH, Grady WM, Halberg RB. Volumetric growth rates of sessile serrated adenomas/polyps observed in situ at longitudinal CT colonography. Eur Radiol 2019; 29:5093-5100. [PMID: 30741343 DOI: 10.1007/s00330-019-5999-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 11/21/2018] [Accepted: 01/04/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Sessile serrated adenomas/polyps (SSA/Ps) are now recognized as potential cancer precursors, but little is known about their natural history. We assessed the in vivo growth rates of histologically proven SSA/Ps at longitudinal CT colonography (CTC) and compared results with non-advanced tubular adenomas (TAs). METHODS We identified a cohort of 53 patients (mean age, 54.8 ± 5.5 years; M:F, 26:27) from one center with a total of 58 SSA/Ps followed longitudinally at CTC (mean follow-up interval, 5.3 ± 1.9 years). Initial and final size measurements were determined using dedicated CTC software. Findings were compared with 141 non-advanced TAs followed at CTC (mean, 4.1 ± 2.3 years) in 113 patients (mean age, 56.8 ± 6.9 years). RESULTS SSA/Ps were more often flat (62% [36/58] vs. 14% [20/141], p < 0.0001) and right-sided (98% [57/58] vs. 46% [65/141], p < 0.0001) compared with TAs. Initial average diameter was greater for SSA/Ps (9.3 mm vs. 6.3 mm; p < 0.0001). Mean annual volumetric growth was + 12.7%/year for SSA/Ps vs. + 36.4%/year for TAs (p = 0.028). Using a previously defined threshold of + 20% increase in volume/year to define progression, 22% (13/58) of SSA/Ps and 41% (58/141) of TAs progressed (p = 0.014). None of the SSA/Ps had dysplasia or invasive cancer at histopathology. CONCLUSIONS Sessile serrated adenoma/polyps demonstrate slower growth compared with conventional non-advanced tubular adenomas, despite larger initial linear size. This less aggressive behavior may help explain the more advanced patient age for serrated pathway cancers. Furthermore, these findings could help inform future colonoscopic surveillance strategies, as current guidelines are largely restricted to expert opinion related to the absence of natural history data. KEY POINTS • Sessile serrated adenoma/polyps (SSA/Ps) tend to be flat, right-sided, and demonstrate slower growth compared with conventional non-advanced tubular adenomas. • This less aggressive behavior of SSA/Ps may help explain the more advanced patient age for serrated pathway cancers.
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Affiliation(s)
- P J Pickhardt
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. .,Department of Radiology, University of Wisconsin School of Medicine and E3/311 Clinical Science Center, 600 Highland Ave., Madison, WI, 53792-3252, USA.
| | - B D Pooler
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - K A Matkowskyj
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - D H Kim
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - W M Grady
- Fred Hutchinson Cancer, University of Washington, Seattle, WA, USA
| | - R B Halberg
- University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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23
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Crockett SD, Gourevitch RA, Morris M, Carrell DS, Rose S, Shi Z, Greer JB, Schoen RE, Mehrotra A. Endoscopist factors that influence serrated polyp detection: a multicenter study. Endoscopy 2018; 50:984-992. [PMID: 29689571 PMCID: PMC6160341 DOI: 10.1055/a-0597-1740] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Serrated polyps are important colorectal cancer precursors that are variably detected during colonoscopy. We measured serrated polyp detection rate (SPDR) in a large, multicenter, cross-sectional study of colonoscopy quality to identify drivers of SPDR variation. METHODS Colonoscopy and pathology reports were collected for a 2-year period (10/2013-9/2015) from four sites across the United States. Data from reports, including size, location, and histology of polyps, were abstracted using a validated natural language processing algorithm. SPDR was defined as the proportion of colonoscopies with ≥ 1 serrated polyp (not including hyperplastic polyps). Multivariable logistic regression was performed to determine endoscopist characteristics associated with serrated polyp detection. RESULTS A total of 104 618 colonoscopies were performed by 201 endoscopists who varied with respect to specialty (86 % were gastroenterologists), sex (18 % female), years in practice (range 1 - 51), and number of colonoscopies performed during the study period (range 30 - 2654). The overall mean SPDR was 5.1 % (SD 3.8 %, range 0 - 18.8 %). In multivariable analysis, gastroenterology specialty training (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.33 - 2.70), fewer years in practice (≤ 9 years vs. ≥ 27 years: OR 1.52, 95 %CI 1.14 - 2.04)], and higher procedure volumes (highest vs. lowest quartile: OR 1.77, 95 %CI 1.27 - 2.46)] were independently associated with serrated polyp detection. CONCLUSIONS Gastroenterology specialization, more recent completion of training, and greater procedure volume are associated with serrated polyp detection. These findings imply that both repetition and training are likely to be important contributors to adequate detection of these important cancer precursors. Additional efforts to improve SPDR are needed.
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Affiliation(s)
- Seth D. Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
| | | | - Michele Morris
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - David S. Carrell
- Kaiser Permanente of Washington Health Research Institute, Seattle, Washington, United States
| | - Sherri Rose
- Harvard Medical School, Boston, Massachusetts, United States
| | - Zhuo Shi
- Harvard Medical School, Boston, Massachusetts, United States
| | - Julia B. Greer
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
| | - Robert E. Schoen
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
| | - Ateev Mehrotra
- Harvard Medical School, Boston, Massachusetts, United States
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24
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Shah J, Shahidullah A. Spontaneous Expulsion per Rectum of a Colorectal Polyp: A Rare and Unusual Case. Gastroenterology Res 2018; 11:329-332. [PMID: 30116435 PMCID: PMC6089584 DOI: 10.14740/gr1054w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 06/12/2018] [Indexed: 12/31/2022] Open
Abstract
Colorectal polyps are growths that form on the epithelium of the colon and rectum. While their prevalence varies considerably from region to region, they are common in adults. In fact, among asymptomatic, average-risk individuals at 50 years of age, the prevalence of colorectal polyps averages roughly 10% in sigmoidoscopy studies and more than 25% in colonoscopy studies. Approximately two-thirds of all colorectal polyps are adenomatous precancerous lesions that have the potential to become malignant. Usually, they are discovered and resected during colonoscopy. The spontaneous expulsion per rectum of a colorectal polyp is exceedingly rare. Here, we report a rare and unusual case that we believe is the first of spontaneous expulsion of an adenomatous polyp during defecation. These patients should undergo colonoscopy to search for additional polyps as well as other gastrointestinal pathology.
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Affiliation(s)
- Jamil Shah
- Department of Internal Medicine, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, 121 Dekalb Avenue, Brooklyn, NY 11201, USA
| | - Abul Shahidullah
- Department of Medicine, Henry J. Carter Specialty Hospital and Nursing Facility, 1752 Park Avenue, New York, NY 10035, USA
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25
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Pioche M, Denis A, Allescher HD, Andrisani G, Costamagna G, Dekker E, Fockens P, Gerges C, Groth S, Kandler J, Lienhart I, Neuhaus H, Petruzziello L, Schachschal G, Tytgat K, Wallner J, Weingart V, Touzet S, Ponchon T, Rösch T. Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study. Gastrointest Endosc 2018; 88:107-116. [PMID: 29410020 DOI: 10.1016/j.gie.2018.01.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 01/18/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Numerous randomized studies have shown that changing certain features of colonoscopes, usually incorporated when switching from one endoscope generation to the next, mostly do not increase adenoma yield. There is, however, indirect evidence that it may be necessary to skip one instrument generation (ie, changing from one generation to the next but one) to achieve this effect. METHODS We compared the latest-generation colonoscopes from one company (Olympus Exera III, 190-C) with the next to last one (Olympus 160/5-C) in a prospective multicenter study randomized for the order of colonoscopes in a tandem fashion, involving 2 different examiners. Patients with increased risk for colorectal neoplasia undergoing colonoscopy (positive fecal occult blood test, personal/familial history of colorectal cancer/adenoma, rectal bleeding, recent change in bowel movements) were included. The primary outcome was the adenoma miss rate with the 190 (190-C) colonoscope in comparison with the 160/5 colonoscope (160/5-C). RESULTS A total of 856 patients (48.8% male; mean age, 58.3 years) with a personal (41%) or family (38%) history of colorectal neoplasia, rectal bleeding (19%), and other indications were included. Of the 429 patients in the 190-C first group, 16.6% (95% confidence interval [CI], 13.0%-20.1%) had at least one adenoma missed during the first procedure, compared with 30.2% (95% CI, 25.9%-34.6%) in the group with 160/5-C first (P < .001). Similarly, the adenoma detection rate during the first colonoscopy was 43.8% versus 36.5% (P = .030) for 190-C versus 160/5-C, respectively. CONCLUSIONS This randomized tandem trial showed lower adenoma miss rates and higher adenoma detection rates for the newer 190 colonoscopes compared with the 160/5 series. These results suggest that it takes multiple improvements, such as those implemented over 2 instrument generations, before an effect on adenoma (miss) rate can be observed. (Study registration number: ISRCTN 2010-A01256-33.).
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Affiliation(s)
- Mathieu Pioche
- Gastroenterology and Endoscopy Division, Hôpital Edouard Herriot, Lyon, France
| | - Angélique Denis
- Hospices Civils de Lyon, Pôle Information médicale Evaluation Recherche, Lyon, France; Université de Lyon, Laboratoire Health Services and Performance Research (HESPER) Lyon, France
| | - Hans-Dieter Allescher
- Department of Medicine, Klinikum Garmisch-Partenkirchen, Academic Teaching Hospital of the LMU Munich, Garmisch-Partenkirchen, Germany
| | | | | | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Christian Gerges
- Department of Gastroenterology, Evangelisches Krankenhaus, Dusseldorf, Germany
| | - Stefan Groth
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Jennis Kandler
- Department of Gastroenterology, Evangelisches Krankenhaus, Dusseldorf, Germany
| | - Isabelle Lienhart
- Gastroenterology and Endoscopy Division, Hôpital Edouard Herriot, Lyon, France
| | - Horst Neuhaus
- Department of Gastroenterology, Evangelisches Krankenhaus, Dusseldorf, Germany
| | | | - Guido Schachschal
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Kristien Tytgat
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands
| | - Jürgen Wallner
- Department of Medicine, Klinikum Garmisch-Partenkirchen, Academic Teaching Hospital of the LMU Munich, Garmisch-Partenkirchen, Germany
| | - Vincens Weingart
- Department of Medicine, Klinikum Garmisch-Partenkirchen, Academic Teaching Hospital of the LMU Munich, Garmisch-Partenkirchen, Germany
| | - Sandrine Touzet
- Hospices Civils de Lyon, Pôle Information médicale Evaluation Recherche, Lyon, France; Université de Lyon, Laboratoire Health Services and Performance Research (HESPER) Lyon, France
| | - Thierry Ponchon
- Gastroenterology and Endoscopy Division, Hôpital Edouard Herriot, Lyon, France
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
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26
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Liu TY, Jin DC, Khan S, Chen X, Shi T, Dong WX, Qi YR, Guo ZX, Wang BM, Cao HL. Clinicopathological features of advanced colorectal serrated lesions: A single-center study in China. J Dig Dis 2018. [PMID: 29542866 DOI: 10.1111/1751-2980.12589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE A growing body of evidence indicates that patients with colorectal serrated lesions, especially advanced serrated lesions (ASLs), are at risk of subsequent malignancy. This study aimed to analyze the clinicopathological features of ASLs and the association between ASLs and synchronous advanced colorectal neoplasia (sACN) in a single center of China. METHODS A retrospective cross-sectional study of consecutive symptomatic patients and healthy individuals who underwent colonoscopy between January 2010 and March 2016 was performed. Clinicopathological characteritics of the patients with ASLs were documented from the colonoscopy database. RESULTS Colorectal serrated lesions were pathologically confirmed in 277 (N = 38 981, 0.7%) cases. Among them, 156 (56.3%) were found to have ASLs, with a total of 161 lesions including 71 sessile serrated adenoma/polyps (SSA/P) and 90 traditional serrated adenomas (TSAs). There were no differences in age and gender between the ASL and non-ASL patients. Among the 161 ASLs, 29 (18.0%) were ≥10 mm in diameter. Compared with non-ASLs, ASLs appeared more in the proximal colon (P = 0.007). Flat and subpedunculated lesions were more commonly found in the ASL group compared with the non-ASL group. Nearly all ASLs (160/161) had dysplasia. Moreover, 16 sACN lesions were found in 156 ASL patients, and large diameter (≥10 mm) might be a significant risk factor for sACN (odds ratio 4.35, 95% confidence interval 1.467-12.894, P < 0.05). CONCLUSIONS ASLs are more likely to occur in the proximal colon, and mainly present as flat and sub-pedunculated types. Large ASLs are significantly associated with sACN.
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Affiliation(s)
- Tian Yu Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Duo Chen Jin
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Samiullah Khan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Xue Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Tao Shi
- Department of Pathology, Tianjin Medical University General Hospital, Tianjin, China
| | - Wen Xiao Dong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Yan Rong Qi
- Department of Gastroenterology and Hepatology, Tianjin Haibin People's Hospital, Tianjin, China
| | - Zi Xuan Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Bang Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Hai Long Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
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27
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Fan C, Younis A, Bookhout CE, Crockett SD. Management of Serrated Polyps of the Colon. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2018; 16:182-202. [PMID: 29445907 PMCID: PMC6284520 DOI: 10.1007/s11938-018-0176-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the management of serrated colorectal polyps (SPs), with a particular focus on the most common premalignant SP, sessile serrated adenoma or polyp (SSA/P). These lesions present a challenge for endoscopists with respect to detection and resection, and are also susceptible to pathologic misdiagnosis. RECENT FINDINGS Patients with SSA/Ps are at an increased risk of future colorectal neoplasia, including advanced polyps and cancer. Reasonable benchmarks for SP detection rates are 5-7% for SSA/Ps and 10-12% for proximal SPs. Certain endoscopic techniques such as chromoendoscopy, narrow band imaging, water immersion, and wide-angle viewing may improve SSA/P detection. Emerging endoscopic techniques such as underwater polypectomy, suction pseudopolyp technique, and piecemeal cold snare polypectomy are helpful tools for the endoscopist's armamentarium for removing SSA/Ps. Proper orientation of SSA/P specimens can improve the accuracy of pathology readings. Patients with confirmed SSA/Ps and proximal HPs should undergo surveillance at intervals similar to what is recommended for patients with conventional adenomas. Patients with SSA/Ps may also be able to lower their risk of future polyps by targeting modifiable risk factors including tobacco and alcohol use and high-fat diets. NSAIDs and aspirin appear to be protective agents. SPs and SSA/Ps in particular are important colorectal cancer precursors that merit special attention to ensure adequate detection, resection, and surveillance.
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Affiliation(s)
- Claire Fan
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Adam Younis
- Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Christine E Bookhout
- Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, CB#7080, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
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Senore C, Bellisario C, Segnan N. Distribution of colorectal polyps: Implications for screening. Best Pract Res Clin Gastroenterol 2017; 31:481-488. [PMID: 28842058 DOI: 10.1016/j.bpg.2017.04.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 04/16/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND During the last decades data from different studies reported modifications of the topographic distribution of colorectal cancers (CRCs), with an increased frequency of tumours in proximal colonic segments. Given the documented link between adenomas and CRC, a proximal migration of adenomas over time could be expected as well. AIM To evaluate available evidence about the prevalence of adenomas and of sessile serrated polyps across colonic segments, the changing trends in their distribution across the colon and the diagnostic performance of screening tests currently adopted in population based screening programs for lesions located in different colonic segments. METHODS Literature search on PubMed, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects with reference to preferred reporting items for systematic reviews and meta-analysis (PRISMA), considering all adult human studies in English, published between January 2000 and February 2017. RESULTS Cross-sectional analysis of endoscopy and pathology data-bases are consistently showing a trend toward an increase with age of the proportion of adenomas located in the proximal colon. Several observational studies analysed the site distribution of adenomas, testing the hypothesis of a proximal shift of these lesions, and most of them reported an increase in the proportion of right-sided adenomas over time, although a similar trend was not confirmed by others. Also the quality of the retrieved evidence was low. Both endoscopy and FIT are showing a different level of sensitivity for lesions arising in different colonic segments, depending also on screenees characteristics. CONCLUSION Available evidence is supporting the hypothesis of an increase in the proportion of right-sided adenomas with age, while a similar increase has not been reported for SSP/A, at least among subjects aged 50 or older. The trend toward a proximalization of colorectal adenomas over time, reported by some authors, likely results from improved diagnostic performances and/or the process of population ageing.
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Affiliation(s)
- Carlo Senore
- AOU Città della Salute e della Scienza, SC Epidemiologia, screening, registro tumori - CPO, Turin, Italy.
| | - Cristina Bellisario
- AOU Città della Salute e della Scienza, SC Epidemiologia, screening, registro tumori - CPO, Turin, Italy
| | - Nereo Segnan
- AOU Città della Salute e della Scienza, SC Epidemiologia, screening, registro tumori - CPO, Turin, Italy
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