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Utsumi T, Yamada Y, Diaz-Meco MT, Moscat J, Nakanishi Y. Sessile serrated lesions with dysplasia: is it possible to nip them in the bud? J Gastroenterol 2023; 58:705-717. [PMID: 37219625 PMCID: PMC10366009 DOI: 10.1007/s00535-023-02003-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/14/2023] [Indexed: 05/24/2023]
Abstract
The serrated neoplasia pathway constitutes an "alternative route" to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic (> 10-15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their flat shapes and the relatively short window of this intermediate state make it difficult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identified distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME). Molecular studies at the single-cell level have identified distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignant-SSLs. Recent progress in all aspects of the field has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications.
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Affiliation(s)
- Takahiro Utsumi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yosuke Yamada
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Maria Teresa Diaz-Meco
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA
| | - Jorge Moscat
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA
| | - Yuki Nakanishi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
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Promsorn J, Chadbunchachai P, Somsap K, Paonariang K, Sa-ngaimwibool P, Apivatanasiri C, Lahoud RM, Harisinghani M. Imaging features associated with survival outcomes among colorectal cancer patients with and without KRAS mutation. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-020-00393-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Abstract
Background
Mutations in Kirsten rat sarcoma proto-oncogene (KRAS) have been shown to be associated with advanced-stage colorectal cancer (CRC), negative disease outcomes, and poor response to treatment. The purpose of this study was to investigate which CT features are biomarkers for KRAS gene mutation and impact the survival outcomes of colorectal cancer patients.
Results
Of the 113 CRC patients included in the study, 46 had KRAS mutations (40.71%) and 67 had no mutations (59.29%). Regional lymph node necrosis was the only imaging feature significantly associated with KRAS mutation (P = 0.011). Higher T staging and liver, lung, and distant metastasis were prognostic factors for CRC (P = 0.014, P < 0.001, P = 0.022, P < 0.001, respectively). There were no significant differences in overall survival between patients with KRAS mutations and those without (P = 0.159). However, in patients with no KRAS mutation, those with CRC on the left side had a significantly higher rate of survival than those with CRC on the right (P = 0.005).
Conclusion
Regional lymph node necrosis may be an imaging biomarker of CRC with KRAS mutation, possibly indicating poor prognosis.
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Crockett SD, Nagtegaal ID. Terminology, Molecular Features, Epidemiology, and Management of Serrated Colorectal Neoplasia. Gastroenterology 2019; 157:949-966.e4. [PMID: 31323292 DOI: 10.1053/j.gastro.2019.06.041] [Citation(s) in RCA: 230] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 06/07/2019] [Accepted: 06/15/2019] [Indexed: 12/11/2022]
Abstract
In addition to the adenoma to carcinoma sequence, colorectal carcinogenesis can occur via the serrated pathway. Studies have focused on clarification of categories and molecular features of serrated polyps, as well as endoscopic detection and risk assessment. Guidelines from the World Health Organization propose assigning serrated polyps to categories of hyperplastic polyps, traditional serrated adenomas, and sessile serrated lesions (SSLs). Traditional serrated adenomas and SSLs are precursors to colorectal cancer. The serrated pathway is characterized by mutations in RAS and RAF, disruptions to the Wnt signaling pathway, and widespread methylation of CpG islands. Epidemiology studies of serrated polyps have been hampered by inconsistencies in terminology and reporting, but the prevalence of serrated class polyps is 20%-40% in average-risk individuals; most serrated polyps detected are hyperplastic. SSLs, the most common premalignant serrated subtype, and are found in up to 15% of average-risk patients by high-detecting endoscopists. Variations in rate of endoscopic detection of serrated polyps indicate the need for careful examination, with adequate bowel preparation and sufficient withdrawal times. Risk factors for SSLs include white race, family history of colorectal cancer, smoking, and alcohol intake. Patients with serrated polyps, particularly SSLs and traditional serrated adenomas, have an increased risk of synchronous and metachronous advanced neoplasia. Surveillance guidelines vary among countries, but SSLs and proximal hyperplastic polyps require special attention in assignment of surveillance interval-especially in light of concerns regarding incomplete detection and resection.
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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.
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
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Rubio CA, Edvardsson Å, Björk J, Tuomisto A, Väisänen T, Mäkinen M. Compound traditional serrated adenoma and sessile serrated adenoma. J Clin Pathol 2016; 69:745-6. [DOI: 10.1136/jclinpath-2016-203716] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 04/10/2016] [Indexed: 11/04/2022]
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Burgess NG, Pellise M, Nanda KS, Hourigan LF, Zanati SA, Brown GJ, Singh R, Williams SJ, Raftopoulos SC, Ormonde D, Moss A, Byth K, P'Ng H, McLeod D, Bourke MJ. Clinical and endoscopic predictors of cytological dysplasia or cancer in a prospective multicentre study of large sessile serrated adenomas/polyps. Gut 2016; 65:437-446. [PMID: 25731869 DOI: 10.1136/gutjnl-2014-308603] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Accepted: 02/07/2015] [Indexed: 12/29/2022]
Abstract
OBJECTIVE The serrated neoplasia pathway accounts for up to 30% of all sporadic colorectal cancers (CRCs). Sessile serrated adenomas/polyps (SSA/Ps) with cytological dysplasia (SSA/P-D) are a high-risk serrated CRC precursor with little existing data. We aimed to describe the clinical and endoscopic predictors of SSA/P-D and high grade dysplasia (HGD) or cancer. DESIGN Prospective multicentre data of SSA/Ps ≥20 mm referred for treatment by endoscopic mucosal resection (September 2008-July 2013) were analysed. Imaging and lesion assessment was standardised. Histological findings were correlated with clinical and endoscopic findings. RESULTS 268 SSA/Ps were found in 207/1546 patients (13.4%). SSA/P-D comprised 32.4% of SSA/Ps ≥20 mm. Cancer occurred in 3.9%. On multivariable analysis, SSA/P-D was associated with increasing age (OR=1.69 per decade; 95% CI (1.19 to 2.40), p0.004) and increasing lesion size (OR=1.90 per 10 mm; 95% CI (1.30 to 2.78), p0.001), an 'adenomatous' pit pattern (Kudo III, IV or V) (OR=3.98; 95% CI (1.94 to 8.15), p<0.001) and any 0-Is component within a SSA/P (OR=3.10; 95% CI (1.19 to 8.12) p0.021). Conventional type dysplasia was more likely to exhibit an adenomatous pit pattern than serrated dysplasia. HGD or cancer was present in 7.2% and on multivariable analysis, was associated with increasing age (OR=2.0 per decade; 95% CI 1.13 to 3.56) p0.017) and any Paris 0-Is component (OR=10.2; 95% CI 3.18 to 32.4, p<0.001). CONCLUSIONS Simple assessment tools allow endoscopists to predict SSA/P-D or HGD/cancer in SSA/Ps ≥20 mm. Correct prediction is limited by failure to recognise SSA/P-D which may mimic conventional adenoma. Understanding the concept of SSA/P-D and the pitfalls of SSA/P assessment may improve detection, recognition and resection and potentially reduce interval cancer. TRIAL REGISTRATION NUMBER NCT01368289.
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Affiliation(s)
- Nicholas G Burgess
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
| | - Maria Pellise
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia
| | - Kavinderjit S Nanda
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia
| | - Luke F Hourigan
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia Department of Gastroenterology and Hepatology, Greenslopes Private Hospital, Brisbane, Queensland, Australia
| | - Simon A Zanati
- Department of Gastroenterology and Hepatology, The Alfred Hospital, Melbourne, Victoria, Australia Department of Gastroenterology and Hepatology, Western Hospital, Melbourne, Victoria, Australia
| | - Gregor J Brown
- Department of Gastroenterology and Hepatology, The Alfred Hospital, Melbourne, Victoria, Australia Department of Gastroenterology and Hepatology, Epworth Hospital, Melbourne, Victoria, Australia
| | - Rajvinder Singh
- Department of Gastroenterology and Hepatology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
| | - Stephen J Williams
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia
| | - Spiro C Raftopoulos
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Donald Ormonde
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Alan Moss
- Department of Gastroenterology and Hepatology, Western Hospital, Melbourne, Victoria, Australia
| | - Karen Byth
- University of Sydney NHMRC Clinical Trials Centre, Sydney, New South Wales, Australia
| | - Heok P'Ng
- Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, New South Wales, Australia
| | - Duncan McLeod
- Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, New South Wales, Australia
| | - Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, New South Wales, Australia Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
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Abstract
Colonoscopy offers incomplete protection from colorectal cancer, particularly in the right colon. Part of this inadequacy may be related to serrated neoplasia. Serrated polyps of the colorectum are now understood to be a heterogeneous group of polyps, some of which are cancer precursors, such as the sessile serrated adenoma (SSA) and the traditional serrated adenoma (TSA). In contrast to conventional adenomas, there is limited published literature on the epidemiology and natural history of these lesions. Furthermore, existing guidelines regarding screening and surveillance practices for these polyps are based largely on expert opinion without firm evidence. In this review, we describe the current understanding of the molecular biology, histopathology, and endoscopic features of serrated neoplasia of the colorectum, with an emphasis on aspects relevant to the practicing gastroenterologist.
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Establishing a biological profile for interval colorectal cancers. Dig Dis Sci 2014; 59:2390-402. [PMID: 24839919 DOI: 10.1007/s10620-014-3210-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 05/07/2014] [Indexed: 12/16/2022]
Abstract
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in North America. Screening for CRC and its precursor lesions is highly effective in reducing the incidence and deaths due to the disease. However, there remain a substantial number of individuals who are diagnosed with CRC soon after a negative/clearing colonoscopy with no documented evidence of CRC. The occurrence of these interval CRCs (I-CRCs) reduces the effectiveness of CRC screening and detection tests and has only recently attracted wide spread attention. I-CRCs can be subdivided into those that occur most likely due to the failure of the colonoscopy examination (missed CRC and CRC that developed from missed or incompletely resected precursor lesions) and those that develop rapidly after the colonoscopy (de novo I-CRCs). In this review, we discuss the current literature and present both the clinical and biological factors that have been identified to account for I-CRCs, with a particular focus on the aberrant molecular features that are candidate causative agents for I-CRCs. We conclude additional studies are required to fully understand the molecular features that lead to the development of I-CRCs, which in turn is essential to develop measures to prevent the occurrence of this group of CRCs and thereby improve CRC screening and detection strategies.
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Burgess NG, Tutticci NJ, Pellise M, Bourke MJ. Sessile serrated adenomas/polyps with cytologic dysplasia: a triple threat for interval cancer. Gastrointest Endosc 2014; 80:307-10. [PMID: 24890425 DOI: 10.1016/j.gie.2014.03.050] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2014] [Accepted: 03/27/2014] [Indexed: 02/08/2023]
Affiliation(s)
- Nicholas G Burgess
- Department of Gastroenterology and Hepatology, Westmead Hospital Westmead, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia
| | - Nicholas J Tutticci
- Department of Gastroenterology and Hepatology, Westmead Hospital Westmead, Sydney, New South Wales, Australia
| | - Maria Pellise
- Department of Gastroenterology and Hepatology, Westmead Hospital Westmead, Sydney, New South Wales, Australia
| | - Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, Sydney, New South Wales, Australia, University of Sydney, Sydney, New South Wales, Australia
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Yamane L, Scapulatempo-Neto C, Reis RM, Guimarães DP. Serrated pathway in colorectal carcinogenesis. World J Gastroenterol 2014; 20:2634-2640. [PMID: 24627599 PMCID: PMC3949272 DOI: 10.3748/wjg.v20.i10.2634] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Revised: 06/15/2013] [Accepted: 07/05/2013] [Indexed: 02/06/2023] Open
Abstract
Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.
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Świątkowski M, Meder A, Sobczyński L, Koza J, Szamocka M, Brudny J, Korenkiewicz J. Serrated polyps detected during screening colonoscopies. Contemp Oncol (Pozn) 2014; 18:54-9. [PMID: 24876822 PMCID: PMC4037994 DOI: 10.5114/wo.2014.40435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 03/21/2013] [Accepted: 07/16/2013] [Indexed: 11/17/2022] Open
Abstract
AIM OF THE STUDY It is estimated that between 15% and 35% of sporadic colorectal cancers (CRC) developing from adenomas come from serrated polyps. Currently, the most effective method used to prevent CRC is the removal of adenomas, including serrated polyps, during colonoscopy. The aim of this paper is to analyze the changes characterized as serrated polyps and detected during screening colonoscopies performed as part of the Screening Program for Early Colorectal Cancer Detection (SPED). MATERIAL AND METHODS In our center, as part of the nationwide SPED between 2000 and 2009, 1,442 screening colonoscopies were performed. RESULTS Serrated polyps were found in 11.9% of all patients and in 45.8% of patients who had polyps removed by endoscopy. In screening colonoscopy of the large intestine, the following polyps were found most frequently: hyperplastic, < 1 cm, without a stalk, multiple, located in the distal part of the large intestine, in men and in patients with a first-degree relative with a history of abdominal cancer. Detecting and removing polyps was facilitated by the fact that the cecum was intubated and the bowel preparation had been performed either very well or well. The detection rate of serrated polyps was not influenced by patients' place of residence or their age. CONCLUSIONS Serrated polyps constitute a frequent, and very frequent among removed polyps, abnormality detected during screening colonoscopy.
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Affiliation(s)
- Maciej Świątkowski
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Agnieszka Meder
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Lesław Sobczyński
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Jarosław Koza
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Małgorzata Szamocka
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Janina Brudny
- Chair and Department of Gastroenterology, Vascular and Internal Diseases, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland
| | - Jadwiga Korenkiewicz
- Division of Pathomorphology, Dr Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
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Bettington M, Walker N, Clouston A, Brown I, Leggett B, Whitehall V. The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology 2013; 62:367-86. [DOI: 10.1111/his.12055] [Citation(s) in RCA: 350] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
BACKGROUND Serrated polyps of the large bowel are potentially premalignant, difficult to see, but important to remove. Few studies describe the technique or outcomes of serrated polypectomy. We sought to present outcomes of a series of polypectomies of large serrated polyps in comparison to a series of endoscopic resections of large adenomas. METHODS This retrospective, comparative, single endoscopist study was performed in an outpatient colonoscopy department of a tertiary referral medical center. Patients had outpatient colonoscopy where a large (≥2 cm) serrated polyp or adenoma was removed. Outcomes were completeness of excision and complications of polypectomy. A database of endoscopic polypectomies was reviewed. Polypectomy of large serrated polyps was compared with polypectomy of large adenomas. RESULTS There were 132 large serrated polyps in 112 patients and 563 adenomas in 428 patients. More serrated polyps were right sided (120 of 130, 92.3 %, vs. 379 of 563, 67 %) (p < 0.0001). The serrated polyps were smaller than the adenomas (mean 25.5 ± 7.9 mm standard deviation) versus 36.8 ± 16.9 mm standard deviation (p < 0.001). There were four complications of serrated polypectomy in four patients (4 % of polyps, 5 % of patients): three postpolypectomy bleeds and one postpolypectomy syndrome. There were 33 complications of adenoma removal (31 postpolypectomy bleeding and two postpolypectomy syndrome) (6.9 % of polyps, p = 0.376, 8.4 % of patients, p = 0.371). On follow-up, 36 of 51 patients (71 %) with serrated polyps had metachronous lesions compared to 133 of 298 patients (45 %) with adenomas (p < 0.0001). There were fewer residual polyps in the serrated group (4 of 47 vs. 64 of 298, p = 0.001). CONCLUSIONS Removal of large serrated colorectal polyps is no more complicated than polypectomy of similarly sized adenomas. However, large serrated polyps have a higher rate of metachronous polyps than similarly sized adenomas and surveillance should be adapted to reflect these findings.
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Buda A, De Bona M, Dotti I, Piselli P, Zabeo E, Barbazza R, Bellumat A, Valiante F, Nardon E, Probert CS, Pignatelli M, Stanta G, Sturniolo GC, De Boni M. Prevalence of different subtypes of serrated polyps and risk of synchronous advanced colorectal neoplasia in average-risk population undergoing first-time colonoscopy. Clin Transl Gastroenterol 2012; 3:e6. [PMID: 23238028 PMCID: PMC3365671 DOI: 10.1038/ctg.2011.5] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES: A growing body of evidence indicates that patients with sessile serrated adenoma/polyp (SSA/P) and traditional serrated adenoma (TSA) are at risk for subsequent malignancy. Despite increasing knowledge on histological categorization of serrated polyps (SPs) data are lacking on the actual prevalence and the association of each SP subtype with advanced colorectal neoplasia. METHODS: We prospectively determined the prevalence of different SP subtypes and evaluate the association with synchronous advanced neoplasia in asymptomatic average-risk subjects undergoing first-time colonoscopy. All retrieved polyps were examined by two independent pathologists. Serrated lesions were classified into hyperplastic polyps (HP), SSA/P (without and with cytological dysplasia, SSA/P/DIS), and TSA, and were screened for BRAF and K-ras mutations. RESULTS: Among 258 polyps detected in 985 subjects, the proportion of SSA/P and TSA was 8.9% and 1.9% with an overall prevalence of 2.3% and 0.6%, respectively. SSA/Ps were small without significant difference in their location between proximal and distal colon; TSA were predominantly left-sided. BRAF mutation was common in SSA/Ps and K-ras mutation was present in all TSA. Independent predictors of advanced neoplasia were male sex (odds ratio (OR)=2.0, 95% confidence interval (CI) 1.0–4.0), increasing age (OR=4.5, 95% CI 1.5–13.4 for 50–69 years and OR=9.9, 95% CI 3.1–31.5 for >70 years), current smoking (OR=2.0, 95% CI 1.3–6.8), >3 tubular adenoma (OR=3.6, 95% CI 1.9–6.4), and SSA/P (OR=6.0, 95% CI 1.9–19.5). CONCLUSIONS: The substantial prevalence of BRAF-mutated SSA/P and the independent association with synchronous advanced colorectal neoplasia in asymptomatic average-risk subjects support the overall impact of the serrated pathway on colorectal cancer (CRC) risk in general population. The endoscopic characteristics of SSA/P emphasize the need of high-quality colonoscopy as a key factor for an effective CRC screening program.
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Affiliation(s)
- Andrea Buda
- 1] University of Bristol, School of Clinical Sciences, Bristol, UK [2] University of Padova, Surgical and Gastroenterological Sciences, Padova, Italy
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