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Thompson A, Dierick NR, Heiniger L, Kostalas SN. Health anxiety and work loss in patients diagnosed with serrated polyposis syndrome: A cross sectional study. World J Clin Oncol 2025; 16:97107. [PMID: 39995560 PMCID: PMC11686561 DOI: 10.5306/wjco.v16.i2.97107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 09/04/2024] [Accepted: 11/08/2024] [Indexed: 12/11/2024] Open
Abstract
BACKGROUND Serrated polyposis syndrome (SPS) is a polyposis condition with neoplastic potential, but its psychological impact is not well understood. AIM To assess health anxiety prevalence in a regional Australian cohort of SPS patients and explore factors influencing it, including workforce impacts of regular surveillance. METHODS This cross-sectional study screened patients aged 18-65 undergoing colonoscopy in a regional gastroenterology practice between January 2015 and June 2022. Eligible SPS patients were invited to participate. Data included the Short Health Anxiety Inventory, employment status, and previous demographic and medical findings. RESULTS Health anxiety was found in 21.57% of SPS patients, with anxious patients being significantly more concerned about surveillance (OR = 7.70). Patients lost an average of 11.04 work hours per colonoscopy. CONCLUSION Health anxiety in SPS patients aligns with rates in other gastroenterology populations. Identifying it may improve management, though further research is needed to better understand prevalence and care improvements.
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Affiliation(s)
- Angus Thompson
- School of Clinical Medicine, University of New South Wales, Port Macquarie 2444, New South Wales, Australia
| | - Natalie R Dierick
- School of Clinical Medicine, University of New South Wales, Port Macquarie 2444, New South Wales, Australia
| | - Louise Heiniger
- Department of Gastroenterology, Port Macquarie Gastroenterology, Port Macquarie 2444, New South Wales, Australia
| | - Stuart N Kostalas
- Department of Gastroenterology, Port Macquarie Gastroenterology, Port Macquarie 2444, New South Wales, Australia
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Chawla T, Hurrell C, Keough V, Lindquist CM, Mohammed MF, Samson C, Sugrue G, Walsh C. Canadian Association of Radiologists Practice Guidelines for Computed Tomography Colonography. Can Assoc Radiol J 2024; 75:54-68. [PMID: 37411043 DOI: 10.1177/08465371231182975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023] Open
Abstract
Colon cancer is the third most common malignancy in Canada. Computed tomography colonography (CTC) provides a creditable and validated option for colon screening and assessment of known pathology in patients for whom conventional colonoscopy is contraindicated or where patients self-select to use imaging as their primary modality for initial colonic assessment. This updated guideline aims to provide a toolkit for both experienced imagers (and technologists) and for those considering launching this examination in their practice. There is guidance for reporting, optimal exam preparation, tips for problem solving to attain high quality examinations in challenging scenarios as well as suggestions for ongoing maintenance of competence. We also provide insight into the role of artificial intelligence and the utility of CTC in tumour staging of colorectal cancer. The appendices provide more detailed guidance into bowel preparation and reporting templates as well as useful information on polyp stratification and management strategies. Reading this guideline should equip the reader with the knowledge base to perform colonography but also provide an unbiased overview of its role in colon screening compared with other screening options.
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Affiliation(s)
- Tanya Chawla
- Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
- Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Casey Hurrell
- Canadian Association of Radiologists, Ottawa, Ontario, Canada
| | - Valerie Keough
- Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Chris M Lindquist
- Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Mohammed F Mohammed
- Abdominal Radiology Section, Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Caroline Samson
- Département de Radiologie, Radio-oncologie et Médecine Nucléaire, Université de Montréal, Montreal, Quebec, Canada
| | - Gavin Sugrue
- Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - Cynthia Walsh
- Department of Radiology, Radiation Oncology and Medical Physics, University of Ottawa, Ottawa, Ontario, Canada
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3
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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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Harewood R, Wooldrage K, Robbins EC, Kinross J, von Wagner C, Cross AJ. Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study. Br J Cancer 2022; 126:1744-1754. [PMID: 35149853 PMCID: PMC9174477 DOI: 10.1038/s41416-022-01719-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 01/03/2022] [Accepted: 01/25/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC). METHODS Endoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics. RESULTS Among 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42-3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10-2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20-2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44-4.04), but not PCC (p-heterogeneity = 0.023). CONCLUSIONS Baseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.
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Affiliation(s)
- Rhea Harewood
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK.
| | - Kate Wooldrage
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - Emma C Robbins
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
| | - James Kinross
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Christian von Wagner
- Research Department of Behavioural Science and Health, University College London, London, UK
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Cancer Screening and Prevention Research Group (CSPRG), Department of Surgery and Cancer, Imperial College London, London, UK
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5
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Muller C, Rao VL. Surveillance Recommendation for Colonoscopy after Polypectomy. Gastrointest Endosc Clin N Am 2022; 32:371-384. [PMID: 35361341 DOI: 10.1016/j.giec.2021.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The incidence and mortality of colorectal cancer (CRC) have declined over the past several decades, largely due to improvement and uptake in screening, particularly with colonoscopy. The US Multi-Society Task Force on CRC published guidelines for surveillance after polypectomy in 2012, which were updated in 2020 with some important changes, and this review will provide an updated overview of evidence and outcomes of surveillance after polypectomy. Notable modifications to surveillance guidelines include increasing interval time between colonoscopies from 5 to 7 to 10 years for 1 to 2 low-risk adenomas (<10 mm) and from 3 years to 3 to 5 years when 3 to 4 low-risk adenomas are identified.
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Affiliation(s)
- Charles Muller
- Division of Gastroenterology & Hepatology, Northwestern Memorial Hospital, 259 East Erie, Suite 1600, Chicago, IL 60611, USA. https://twitter.com/cmmuller7
| | - Vijaya L Rao
- Section of Gastroenterology, Hepatology & Nutrition, University of Chicago Medicine, 5841 South Maryland Avenue, Rm S-401, Chicago, IL 60637, USA.
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Chu JE, Hamm J, Gentile L, Telford JJ, Schaeffer DF. Serrated Lesion Detection in a Population-based Colon Screening Program. J Clin Gastroenterol 2022; 56:243-248. [PMID: 33780220 DOI: 10.1097/mcg.0000000000001519] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/28/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND Serrated lesions give rise to 15% to 30% of all colorectal cancers, driven predominantly by the sessile serrated polyp (SSP). Fecal immunochemical test (FIT), has low sensitivity for SSPs. SSP detection rate (SSPDR) is influenced by performance of both endoscopists and pathologists, as diagnosis can be subtle both on endoscopy and histology. GOALS To evaluate the SSPDR in a population-based screening program, and the influence of subspecialty trained pathologists on provincial reporting practices. STUDY The colon screening program database was used to identify all FIT-positive patients that received colonoscopy between January 2014 and June 2017. Patient demographics, colonoscopy quality indicators, pathologic diagnoses, and FIT values were collected. This study received IRB approval. RESULTS A total of 74,605 colonoscopies were included and 26.6% had at least 1 serrated polyp removed. The SSPDR was 7.0%, with 59% of the SSPs detected having a concurrent conventional adenoma. The mean FIT value for colonoscopies with only serrated lesions was less than that for colonoscopies with a conventional adenoma or colorectal cancer (P<0.0001). Centers with a gastrointestinal subspecialty pathologist diagnosed proportionally more SSPs (P<0.0001), and right-sided SSPs than centers without subspecialists. CONCLUSIONS Serrated lesions often occur in conjunction with conventional adenomas and are associated with lower FIT values. Knowledge of the characteristics of SSPs is essential for pathologists to ensure accurate diagnosis of SSPs.
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Affiliation(s)
- Jenny E Chu
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital
| | | | | | - Jennifer J Telford
- BC Cancer
- Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - David F Schaeffer
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital
- BC Cancer
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7
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Muller C, Yamada A, Ikegami S, Haider H, Komaki Y, Komaki F, Micic D, Sakuraba A. Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:622-630.e7. [PMID: 34089849 DOI: 10.1016/j.cgh.2021.05.057] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 05/28/2021] [Accepted: 05/31/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. METHODS Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. RESULTS Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. CONCLUSIONS Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.
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Affiliation(s)
- Charles Muller
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Akihiro Yamada
- Section of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Sachie Ikegami
- Department of Pathology, NorthShore University HealthSystem, Evanston, Illinois
| | - Haider Haider
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Yuga Komaki
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Fukiko Komaki
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Dejan Micic
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois
| | - Atsushi Sakuraba
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago Medicine, Chicago, Illinois.
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Lao W, Prasoon P, Cao G, Tan LT, Dai S, Devadasar GH, Huang X. Risk factors for incomplete polyp resection during colonoscopy. LAPAROSCOPIC, ENDOSCOPIC AND ROBOTIC SURGERY 2021. [DOI: 10.1016/j.lers.2021.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Detection of High-Risk Sessile Serrated Lesions: Multi-Target Stool DNA Versus CT Colonography. AJR Am J Roentgenol 2021; 218:670-676. [PMID: 34755523 DOI: 10.2214/ajr.21.26719] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Background: The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Patients with sessile serrated lesions (SSLs) that are large (≥10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of non-invasive screening tests for detection of high-risk SSLs is unclear. Objective: The aim of this study was to compare non-invasive screen detection of high-risk SSLs between the multi-target stool DNA test (mt-sDNA; Cologuard) and CT colonography (CTC). Methods: This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age 60.0 years) who underwent CRC screening at a single center by mt-sDNA (Cologuard) from 2014-2019 (n=3987) or by CTC from 2009-2019 (n=3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. Results: The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p=.23) and 6.5% (260/3987; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA, versus 14.4% (66/457; p<.001) and 25.9% (63/243; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; p<.001) and 1.6% (63/3987; p<.001) for CTC at 6-mm and 10-mm thresholds, respectively. Conclusions: CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. Clinical Impact: The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.
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Monreal-Robles R, Jáquez-Quintana JO, Benavides-Salgado DE, González-González JA. Serrated polyps of the colon and rectum: a concise review. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 86:276-286. [PMID: 34116964 DOI: 10.1016/j.rgmxen.2021.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
"Serrated polyps" is the term used for epithelial lesions of the colon and rectum that have a "sawtooth" pattern on the polyp's surface and crypt epithelium. The so-called serrated pathway describes the progression of sessile serrated adenomas and traditional serrated adenomas to colorectal cancer. Said pathway is well recognized as an alternative mechanism of carcinogenesis and accounts for 15-30% of the cases of colorectal cancer. It also explains a large number of the cases of interval colorectal cancer. Thus, due to their usually aggressive and uncertain behavior, serrated polyps are of the utmost importance in colorectal cancer screening. Our aim was to review the history, current nomenclature, pathophysiology, morphology, treatment, and surveillance of serrated polyps.
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Affiliation(s)
- R Monreal-Robles
- Servicio de Gastroenterología, Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico; Escuela de Medicina y Ciencias de la Salud, Instituto Tecnológico y de Estudios Superiores de Monterrey, Monterrey, Nuevo León, Mexico.
| | - J O Jáquez-Quintana
- Servicio de Gastroenterología, Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - D E Benavides-Salgado
- Servicio de Gastroenterología, Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - J A González-González
- Servicio de Gastroenterología, Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
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Aoki H, Adachi Y, Yamamoto E, Yoshida Y, Ishii Y, Yamano HO, Suzuki H, Endo T. The continuum of transformation of TSA to low-grade neoplasia and cancer with BRAF mutation - A case with molecular analysis. Pathol Int 2021; 71:368-370. [PMID: 33559224 DOI: 10.1111/pin.13078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/26/2021] [Accepted: 01/31/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Hironori Aoki
- Department of Internal Medicine, Division of Gastroenterology, Sapporo Shirakaba-dai Hospital, Hokkaido, Japan
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Hokkaido, Japan
- Center for Gastroenterology, Teine-Keijinkai Hospital, Hokkaido, Japan
| | - Yasushi Adachi
- Department of Internal Medicine, Division of Gastroenterology, Sapporo Shirakaba-dai Hospital, Hokkaido, Japan
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Eiichiro Yamamoto
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Hokkaido, Japan
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Yukinari Yoshida
- Department of Internal Medicine, Division of Gastroenterology, Sapporo Shirakaba-dai Hospital, Hokkaido, Japan
| | - Yoshifumi Ishii
- Department of Pathology, Sapporo Shirakaba-dai Hospital, Hokkaido, Japan
| | - Hiro-O Yamano
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Hiromu Suzuki
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Hokkaido, Japan
| | - Takao Endo
- Department of Internal Medicine, Division of Gastroenterology, Sapporo Shirakaba-dai Hospital, Hokkaido, Japan
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12
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Discovering the Mutational Profile of Early Colorectal Lesions: A Translational Impact. Cancers (Basel) 2021; 13:cancers13092081. [PMID: 33923068 PMCID: PMC8123354 DOI: 10.3390/cancers13092081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most common malignancies worldwide. Next-generation sequencing technologies have identified new candidate genes and deepened the knowledge of the molecular mechanisms underlying the progression of colonic adenomas towards CRC. The main genetic, epigenetic, and molecular alterations driving the onset and progression of CRC in both hereditary and sporadic settings have also been investigated. The evaluation of the CRC risk based on the molecular characterization of early pre-cancerous lesions may contribute to the development of targeted preventive strategies development, help define specific risk profiles, and identify patients who will benefit from targeted endoscopic surveillance. Abstract Colorectal cancer (CRC) develops through a multi-step process characterized by the acquisition of multiple somatic mutations in oncogenes and tumor-suppressor genes, epigenetic alterations and genomic instability. These events lead to the progression from precancerous lesions to advanced carcinomas. This process requires several years in a sporadic setting, while occurring at an early age and or faster in patients affected by hereditary CRC-predisposing syndromes. Since advanced CRC is largely untreatable or unresponsive to standard or targeted therapies, the endoscopic treatment of colonic lesions remains the most efficient CRC-preventive strategy. In this review, we discuss recent studies that have assessed the genetic alterations in early colorectal lesions in both hereditary and sporadic settings. Establishing the genetic profile of early colorectal lesions is a critical goal in the development of risk-based preventive strategies.
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13
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Pitchumoni CS. Colorectal Cancer. GERIATRIC GASTROENTEROLOGY 2021:1963-1989. [DOI: 10.1007/978-3-030-30192-7_80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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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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Tao EW, Wang YF, Zou TH, Cui Y, Chen YX, Gao QY. Relationship between serrated polyps and synchronous and metachronous advanced neoplasia: A retrospective study. J Dig Dis 2020; 21:558-565. [PMID: 32761806 DOI: 10.1111/1751-2980.12928] [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: 04/22/2020] [Revised: 07/21/2020] [Accepted: 08/02/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Serrated polyps (SP) are regarded as precursor lesions of colorectal cancer (CRC). We conducted this single-center study aiming to investigate the relationship between SP and synchronous and metachronous advanced neoplasia in the Chinese population. METHODS The data for this retrospective study were collected from the Endoscopy Center and Department of Gastroenterology of Renji Hospital, School of Medicine, Shanghai Jiao Tong University between May 2012 and May 2019. Altogether 2205 patients were pathologically confirmed with colorectal SP. RESULTS The detection rate of SP among all polyps has gradually increased since 2014 and reached 8.74% by 2019. Among all the SP cases, 1540 (69.84%) were confirmed as having hyperplasic polyps (HP), 486 (22.04%) were having sessile serrated lesions (SSL), and 171 (7.76%) had traditional serrated adenomas (TSA). Compared with HP (2.14%), SSL and TSA were larger and more likely to be accompanied by synchronous and metachronous advanced neoplasia (6.79% and 6.08%). We next found that large SP (diameter ≥10 mm) (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.40-4.55, P = 0.002) and SSL with high-grade intraepithelial neoplasia (OR 13.85, 95% CI 3.28-58.56, P < 0.001) were associated with an increased risk of synchronous advanced neoplasia. However, we failed to find a relationship between SP and metachronous advanced neoplasia because few patients had developed metachronous advanced neoplasia. CONCLUSION Large SP and SSL with high-grade intraepithelial neoplasia are associated with synchronous advanced neoplasia and require timely surveillance.
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Affiliation(s)
- En-Wei Tao
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yong Feng Wang
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian Hui Zou
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Cui
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Xuan Chen
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qin Yan Gao
- Division of Gastroenterology and Hepatology, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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16
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Hua X, Newcomb PA, Chubak J, Malen RC, Ziebell R, Kamineni A, Zhu LC, Upton MP, Wurscher MA, Thomas SS, Newman H, Hardikar S, Burnett-Hartman AN. Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia. Cancer Causes Control 2020; 31:631-640. [PMID: 32358694 DOI: 10.1007/s10552-020-01304-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 04/24/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia. METHODS Study subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers. RESULTS We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51). CONCLUSION Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.
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Affiliation(s)
- Xinwei Hua
- School of Public Health, University of Washington, Seattle, WA, USA
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Polly A Newcomb
- School of Public Health, University of Washington, Seattle, WA, USA
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Jessica Chubak
- School of Public Health, University of Washington, Seattle, WA, USA
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Rachel C Malen
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Rebecca Ziebell
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Aruna Kamineni
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Lee-Ching Zhu
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Melissa P Upton
- Department of Pathology, University of Washington, Seattle, WA, USA
| | | | | | - Hana Newman
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Sheetal Hardikar
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Andrea N Burnett-Hartman
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Kaiser Permanente Colorado, Institute for Health Research, 2550 S Parker Rd, Suite 200, Waterpark III, 2nd floor, Aurora, CO, 80014, USA.
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17
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Jennings P, Seigneurin A, Delafosse P, Baysson H, Exbrayat C. A twelve-year study of the prevalence, risk factors and characteristics of interval colorectal cancers after negative colonoscopy. Clin Res Hepatol Gastroenterol 2020; 44:230-238. [PMID: 31302010 DOI: 10.1016/j.clinre.2019.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 05/12/2019] [Accepted: 06/13/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The objective of our study was to describe and analyse the Post-Colonoscopy Colorectal Cancers (PCCRCs) and endoscopist performance-related risk factors in the Isère regional screening programme. METHOD This was a population-based retrospective cohort study between 2002-2013, where Post-Colonoscopy Colorectal Cancers (PCCRCs) were defined as colorectal adenocarcinoma diagnosed between six and sixty months post-colonoscopy following a positive gFOBT. We analysed the endoscopist performance-related risk factors of the 62 gastroenterologists who had carried out at least 30 colonoscopies during this period. RESULTS During the period reviewed, there were 10,557 negative colonoscopies performed. Fifteen post-colonoscopy colorectal cancers were diagnosed from 2002-2013 with an average patient age of 67.1 years. Men comprised 73% of the cases and 53% of all the cases were found in the distal colon. These 15 cases comprised 1.1% of all Colorectal Cancers (CRCs) diagnosed in the screening programme, with an incidence rate of 0.42 (0.21-0.77) per 1,000 person-years. The aetiological breakdown was as follows: 47% related to missed cancers, 27% were new cancers, 20% were failed biopsy detection, and 6% related to incomplete removal. The Adenoma Detection Rate (ADR) among gastroenterologists was an average of 30%, but large heterogeneity was present within this number, ranging from 11% to 49%. CONCLUSION The post-colonoscopy colorectal cancer prevalence and incident rate were low relative to the literature. However, significant heterogeneity was present in the adenoma detection rate. Decreasing this heterogeneity by establishing a national benchmark, regular performance feedback and training modules should homogenise adenoma detection rates and decrease the number of interval cancers in the region.
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Affiliation(s)
- Paul Jennings
- Office de lutte contre le cancer, 38240 Meylan, France.
| | - Arnaud Seigneurin
- Registre du cancer de l'Isère, CHU de Grenoble, pavillon E, BP 217, 38043 Grenoble cedex 9, France
| | - Patricia Delafosse
- Registre du cancer de l'Isère, CHU de Grenoble, pavillon E, BP 217, 38043 Grenoble cedex 9, France
| | - Hélène Baysson
- Centre hospitalier Annecy-Genevois, 74370 Metz-Tessy, France
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18
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Multitarget Stool DNA Screening in Clinical Practice: High Positive Predictive Value for Colorectal Neoplasia Regardless of Exposure to Previous Colonoscopy. Am J Gastroenterol 2020; 115:608-615. [PMID: 32068535 PMCID: PMC7127971 DOI: 10.14309/ajg.0000000000000546] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.
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19
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Rameshshanker R, Saunders BP. Number of significant polyps detected per six-minute withdrawal time at colonoscopy (SP6): a new measure of colonoscopy efficiency and quality. Frontline Gastroenterol 2020; 11:491-493. [PMID: 33101628 PMCID: PMC7569513 DOI: 10.1136/flgastro-2019-101184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 01/02/2020] [Accepted: 01/04/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Rajaratnam Rameshshanker
- Wolfson Unit for Endoscopy, St Mark’s Hospital, Harrow, London, UK,Department of Surgery and Cancer, Imperial College London, London, UK
| | - Brian P Saunders
- Wolfson Unit for Endoscopy, St Mark’s Hospital, Harrow, London, UK,Department of Surgery and Cancer, Imperial College London, London, UK
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20
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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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21
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Nakanishi Y, Diaz-Meco MT, Moscat J. Serrated Colorectal Cancer: The Road Less Travelled? Trends Cancer 2019; 5:742-754. [PMID: 31735291 DOI: 10.1016/j.trecan.2019.09.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 09/09/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023]
Abstract
Studies of colorectal cancer (CRC) originating through the conventional adenoma-carcinoma sequence have provided insight into the molecular mechanisms controlling its initiation and progression. Less is known about the alternative 'serrated' pathway, which has been associated with BRAF mutation and microsatellite instability. Recent transcriptomics approaches to classify human CRC revealed that mesenchymal and/or desmoplastic features combined with an immunosuppressive microenvironment are key determinants of CRC with the poorest prognosis. Importantly, these aggressive CRCs harbor the characteristics of serrated tumors, suggesting that initiation through this alternative pathway determines how aggressive the CRC becomes. Here, we review recent evidence on how serrated carcinogenesis contributes to the subtype of CRC with the poorest prognosis.
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Affiliation(s)
- Yuki Nakanishi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Maria T Diaz-Meco
- Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
| | - Jorge Moscat
- Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
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22
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Ahmed S, Galle PR, Neumann H. Molecular endoscopic imaging: the future is bright. Ther Adv Gastrointest Endosc 2019; 12:2631774519867175. [PMID: 31517311 PMCID: PMC6724493 DOI: 10.1177/2631774519867175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 07/10/2019] [Indexed: 12/24/2022] Open
Abstract
The prediction and final survival rate of gastrointestinal cancers are dependent on the stage of disease. The ideal would be to detect those gastrointestinal lesions at early stage or even premalignant forms which are difficult to detect by conventional endoscopy with white light optical imaging as they show minimum or no changes in morphological characteristics and are thus left untreated. The introduction of molecular imaging has greatly changed the pattern for detecting gastrointestinal lesions from purely macroscopic structural imaging to the molecular level. It allows microscopic examination of the gastrointestinal mucosa with endoscopy after the topical or systemic application of molecular probes. In recent years, major advancements in endoscopic instruments and specific molecular probes have been achieved. This review focuses on the current status of endoscopic imaging and highlights the application of molecular imaging in gastrointestinal and hepatic disease in the context of diagnosis and therapy based on recently published literature in this field. We also discuss the challenges of molecular endoscopic imaging, its future directions and potential that could have a tremendous impact on endoscopic research and clinical practice in future.
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Affiliation(s)
- Shakil Ahmed
- Department of Interdisciplinary Endoscopy, I. Medical Clinic and Polyclinic, University Hospital Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Peter R Galle
- Department of Interdisciplinary Endoscopy, I. Medical Clinic and Polyclinic, University Hospital Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Helmut Neumann
- Department of Interdisciplinary Endoscopy, I. Medical Clinic and Polyclinic, University Hospital Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
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23
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Hissong E, Fernandes H, Jessurun J. Colonic Mucosa With Polypoid Hyperplasia. Am J Clin Pathol 2019; 152:423-430. [PMID: 31152544 DOI: 10.1093/ajcp/aqz053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES Define the morphologic and molecular features of colonic polyps with subtle histologic features. METHODS Two hundred specimens were obtained of surveillance colonoscopies. Endoscopic findings were reviewed. Histologic features of the polyps were compared with the flat mucosa. Next-generation sequencing was performed on 30 study polyps and 20 control samples. RESULTS Polyps with subtle changes comprised 12% of all polyps. All polyps were sessile and small (<0.5 cm) and were located predominantly in the distal colon (60%). Synchronous hyperplastic, sessile serrated, and dysplastic polyps were found in 30%, 7%, and 51% of patients, respectively. A total of 169 (84.5%) polyps showed wide, nonserrated crypts, increased intraluminal mucus, and patent openings. KRAS alterations were present in 30% of polyps. CONCLUSIONS Most polyps with subtle histologic features have recognizable morphologic changes. About one-third harbored KRAS alterations. These polyps should not be regarded as variants of hyperplastic polyps.
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Affiliation(s)
- Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Helen Fernandes
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY
| | - Jose Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
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Rönnow CF, Uedo N, Stenfors I, Toth E, Thorlacius H. Forceps Biopsies Are Not Reliable in the Workup of Large Colorectal Lesions Referred for Endoscopic Resection: Should They Be Abandoned? Dis Colon Rectum 2019; 62:1063-1070. [PMID: 31318770 DOI: 10.1097/dcr.0000000000001440] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Biopsies are routinely obtained in the workup of large colorectal polyps before endoscopic resection. OBJECTIVE This study aimed to examine how reliable biopsies are in terms of reflecting the true histopathology of large colorectal polyps, in the clinical routine. DESIGN This is a retrospective study. SETTINGS Data from patients undergoing polypectomy of large colorectal polyps at the endoscopy unit, Skåne University Hospital Malmö, between January 2014 and December 2016 were scrutinized. PATIENTS A total of 485 colorectal lesions were biopsied within 1 year before complete endoscopic removal. Biopsy-obtained specimens were compared with completely resected specimens in terms of concordance and discordance and if the final result was upgraded or downgraded. MAIN OUTCOME MEASURES The primary outcome measured was the concordance between biopsy-obtained specimens and completely resected specimens. RESULTS Median lesion size was 3 cm (range 1-11). In 189 cases (39%), biopsies did not provide a correct dysplastic grade compared with final pathology after complete resection. One hundred forty-three cases (29%) and 46 cases (9%) were upgraded and downgraded. The percentage of cases with discordant biopsy results was 40% in cases with 1 biopsy taken and 38% in cases where multiple biopsies had been sampled. Time from biopsy to complete resection did not influence the erroneous outcome of biopsies. Notably, the percentage of discordant biopsy results was 37% and 35% in lesions measuring 1 to 2 cm and 2 to 4 cm. However, this percentage increased to 48% in colorectal lesions larger than 4 cm. LIMITATIONS This study was designed to reflect the clinical routine, the number of biopsies obtained and forceps technique were hence not standardized, which constitutes a limitation. CONCLUSIONS This study demonstrates that cancer-negative forceps biopsies of large colorectal polyps, referred for endoscopic resection, are not reliable. Considering that endoscopic resection of lesions containing superficial cancer is plausible, the clinical value of forceps biopsies in lesions suitable for endoscopic resection is questionable. See Video Abstract at http://links.lww.com/DCR/A984. LAS BIOPSIAS CON FÓRCEPS NO SON CONFIABLES EN EL ESTUDIO DE LAS LESIONES COLORRECTALES GRANDES REFERIDAS PARA RESECCIÓN ENDOSCÓPICA: ¿DEBERÍAN ABANDONARSE?: Las biopsias se obtienen de forma rutinaria en el estudio de pólipos colorrectales grandes previo a resección endoscópica. OBJETIVO Analizar que tan confiables son las biopsias en cuanto a reflejar la verdadera histopatología de los pólipos colorrectales grandes, en la rutina clínica. DISEÑO:: Este es un estudio retrospectivo. AJUSTES Los datos de pacientes sometidos a polipectomía de pólipos colorrectales grandes en la unidad de endoscopia, en Skåne University Hospital Malmö, entre enero de 2014 y diciembre de 2016 fueron examinados. PACIENTES Un total de 485 lesiones colorrectales se biopsiaron dentro de un año antes de la resección endoscópica completa. Las muestras obtenidas mediante biopsia se compararon con las muestras completas resecadas en términos de concordancia y discordancia, y si el resultado final ascendió o disminuyó de categoría. PRINCIPALES MEDIDAS DE RESULTADO Concordancia entre muestras obtenidas mediante biopsia y muestras completamente resecadas. RESULTADOS La mediana de tamaño de lesiones fue de 3 cm (rango 1-11). En 189 casos (39%) las biopsias no proporcionaron un grado de displasia correcto en comparación con la patología final después de la resección completa. 143 casos (29%) y 46 casos (9%) ascendieron y descendieron de categoría, respectivamente. El porcentaje de casos con resultados de biopsia discordantes fue del 40% en los casos con una sola biopsia tomada y del 38% en los casos en los que se tomaron múltiples biopsias. El tiempo desde la biopsia hasta la resección completa no influyó en el resultado erróneo de las biopsias. Notablemente, el porcentaje de resultados de biopsia discordantes fue de 37% y 35% en lesiones que midieron 1-2 cm y 2-4 cm, respectivamente. Sin embargo, este porcentaje aumentó a 48% en lesiones colorrectales mayores de 4 cm. LIMITACIONES Este estudio se diseñó para reflejar la rutina clínica, el número de biopsias obtenidas y la técnica de fórceps no fueron estandarizadas, lo que constituye una limitación. CONCLUSIONES Este estudio demuestra que las biopsias con fórceps negativas a cáncer, de pólipos colorrectales grandes referidas para resección endoscópica, no son confiables. Teniendo en cuenta que la resección endoscópica de lesiones que contienen cáncer superficial es posible, el valor clínico de las biopsias con fórceps en lesiones aptas para la resección endoscópica es cuestionable. Vea el Resumen en video en http://links.lww.com/DCR/A984.
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Affiliation(s)
- Carl-Fredrik Rönnow
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Iréne Stenfors
- Section of Gastroenterology, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Ervin Toth
- Section of Gastroenterology, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Henrik Thorlacius
- Section of Surgery, Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden
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Villanacci V, Baronchelli C, Manenti S, Bassotti G, Salviato T. Serrated lesions of the colon A window on a more clear classification. Ann Diagn Pathol 2019; 41:8-13. [PMID: 31112900 DOI: 10.1016/j.anndiagpath.2019.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/11/2019] [Indexed: 01/26/2023]
Abstract
Serrated polyps evaluation represents a challenge for pathologists for lacking of univocal criteria that leads to different inter -individual interpretation. The aim of our review is to offer an alternative simpler histologic and endoscopic approach to these lesions for a more correct relationship between endoscopists and pathologists.
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Affiliation(s)
| | | | | | - Gabrio Bassotti
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia, Italy
| | - Tiziana Salviato
- Pathology Institute, Azienda Ospedaliera Universitaria, Ospedali Riuniti di Trieste, Trieste, Italy.
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26
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Clinicopathologic and genetic characteristics of interval colorectal carcinomas favor origin from missed or incompletely excised precursors. Mod Pathol 2019; 32:666-674. [PMID: 30455417 DOI: 10.1038/s41379-018-0176-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 10/30/2018] [Accepted: 10/31/2018] [Indexed: 12/17/2022]
Abstract
Interval colorectal cancers may arise from missed or incompletely excised precursors or from a unique rapid progression pathway. We compared the clinicopathologic and molecular profiles of interval and matched non-interval colorectal cancer to determine whether interval colorectal cancers harbor any unique genetic characteristics. Fifty one of 982 colorectal cancer (5.2%) were categorized as interval colorectal cancer, defined as colorectal cancer detected in a diagnostic examination prior to the next recommended colonoscopy and at least 1 year after the last colonoscopy. Clinicopathologic characteristics of interval colorectal cancer were compared to non-interval colorectal cancer matched 1:1 on age, gender, and tumor location. Molecular profile of a subset of interval colorectal cancer (n = 20) and matched (1:2) non-interval colorectal cancer (n = 40) were evaluated using next generation sequencing. Interval colorectal cancer were more likely to occur in the right colon (55% vs. 35%; p = 0.02) and in patients > 70 years of age (55% vs. 34%; p = 0.002). Clinicopathologic features and aberrant DNA mismatch repair protein expression were not significantly different between interval and matched non-interval colorectal cancer. The frequency and spectrum of genetic alterations was also similar in interval and matched non-interval colorectal cancer. Similar findings were seen when analysis was restricted to interval colorectal cancer diagnosed <5 years after last colonoscopy (n = 42). Interval and non-interval colorectal cancers share similar clinicopathologic and genetic profiles when matched for tumor location. Interval colorectal cancers and are more likely to develop from missed or incompletely excised precursors rather than a unique rapid progression pathway.
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27
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Leung JW, Yen AW, Jia H, Opada C, Melnik A, Atkins J, Feller C, Wilson MD, Leung FW. A prospective RCT comparing combined chromoendoscopy with water exchange (CWE) vs water exchange (WE) vs air insufflation (AI) in adenoma detection in screening colonoscopy. United European Gastroenterol J 2019; 7:477-487. [PMID: 31065365 DOI: 10.1177/2050640619832196] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 01/22/2019] [Indexed: 12/15/2022] Open
Abstract
Background A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. Aims We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. Methods After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. Results Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. Conclusions When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).
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Affiliation(s)
- J W Leung
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA.,Division of Gastroenterology and Hepatology, University of California, Davis School of Medicine, Sacramento, CA, USA
| | - A W Yen
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - H Jia
- Department of Gastroenterology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - C Opada
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - A Melnik
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - J Atkins
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - C Feller
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - M D Wilson
- Clinical and Translational Science Center, Department of Public Health Sciences, Division of Biostatistics, University of California, Davis, Sacramento, CA, USA
| | - F W Leung
- Sepulveda Ambulatory Care Center, Veteran Affairs Greater Los Angeles Healthcare System (VAGLAHS) and David Geffen School of Medicine at UCLA, North Hills, CA, USA
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28
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Cassese G, Amendola A, Maione F, Giglio MC, Pagano G, Milone M, Aprea G, Luglio G, De Palma GD. Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management. Gastroenterol Res Pract 2019; 2019:9179718. [PMID: 30774654 PMCID: PMC6350577 DOI: 10.1155/2019/9179718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023] Open
Abstract
Prompt diagnosis and correct management of the so called "serrated lesions" (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
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Affiliation(s)
- Gianluca Cassese
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Alfonso Amendola
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Francesco Maione
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Mariano Cesare Giglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gianluca Pagano
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Marco Milone
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Aprea
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gaetano Luglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Domenico De Palma
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
- Center of Excellence for Technological Innovation in Surgery, University of Naples “Federico II”, Italy
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29
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Hirai HW, Ching JYL, Wu JCY, Sung JJY, Chan FKL, Ng SC. Risk factors for advanced colorectal neoplasms in the proximal colon in 6218 subjects undergoing complete colonoscopy. J Gastroenterol Hepatol 2019; 34:113-119. [PMID: 29932241 DOI: 10.1111/jgh.14357] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 06/13/2018] [Accepted: 06/14/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Proximal migration of colonic lesion has been observed; however, risk factors of lesions in the proximal colon remain uncertain. This study aimed to investigate risk factors of lesions in the proximal colon. METHODS Consecutive subjects with complete colonoscopy were included. The primary outcome was risk factors associated with advanced neoplasm (AN) and serrated lesion in the proximal colon. Age, gender, first-degree relative (FDR) with colorectal cancer (CRC), smoking, alcohol consumption, body mass index, hypertension, diabetes, ischemic heart disease, and the use of aspirin, non-steroidal anti-inflammatory drug, and anticoagulants were fitted into a regression model, with reference to subjects without colonic finding. Results were measured by odds ratio (OR) with 95% confidence interval (CI). RESULTS Among 6218 subjects (mean age 56.65 ± 6.15 years; 46.8% male), 352 (5.7%) had AN; 809 (13.0%) had serrated lesions, and 3648 (58.7%) had no colonic finding. There were 148 (2.4%) and 235 (3.8%) subjects having AN and serrated lesion in the proximal colon. Age ≥ 50 (OR: 13.30; 95% CI: 1.85-95.76), male gender (OR: 1.82; 95% CI: 1.26-2.62), FDR with CRC (OR: 2.12; 95% CI: 1.43-3.15), and hypertension (OR: 1.86; 95% CI: 1.30-2.68) were associated with AN in the proximal colon. Age ≥ 50 (OR: 5.72; 95% CI: 2.10-15.53), male gender (OR: 1.54; 95% CI: 1.15-2.05), and smoking (OR: 1.85; 95% CI: 1.23-2.79) increased risk of serrated lesions in the proximal colon. CONCLUSION Age ≥ 50 and male gender were associated with both proximally located AN and serrated lesion; FDR with CRC and hypertension increased the risk of proximal AN, while ever smoking increased the risk of proximal serrated lesion. FDR with CRC was not associated with serrated lesion.
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Affiliation(s)
- Hoyee W Hirai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Jessica Y L Ching
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Francis K L Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Siew C Ng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
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30
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Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology 2019; 156:218-226. [PMID: 30340754 DOI: 10.1053/j.gastro.2018.07.016] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
| | - Katarina B Greer
- Division of Gastroenterology and Liver Disease, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Joel J Heidelbaugh
- Departments of Family Medicine and Urology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Yngve Falck-Ytter
- Division of Gastroenterology, Case Western Reserve University and Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio
| | - Brian J Hanson
- Division of Gastroenterology, University of Minnesota and Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota
| | - Shahnaz Sultan
- Division of Gastroenterology, University of Minnesota and Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota
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31
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A Retrospective Analysis of Colorectal Serrated Lesions from 2005 to 2014 in a Single Center: Importance of the Establishment of Diagnostic Patterns. Gastroenterol Res Pract 2018; 2018:5946057. [PMID: 30420877 PMCID: PMC6215568 DOI: 10.1155/2018/5946057] [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: 07/23/2018] [Accepted: 09/03/2018] [Indexed: 11/17/2022] Open
Abstract
Background Serrated colorectal lesions are increasingly recognized as an important process in the development of colorectal cancer. Endoscopic and histological diagnosis may be difficult, and knowledge of the serrated lesions is important for the establishment of strategies for treating colorectal lesions. We aimed to analyze serrated lesions diagnosed at a single center and evaluate if there was an increase in their identification over the years. Design and Setting A retrospective analysis of colonoscopy reports was performed at a specialized center from 2005 to 2014. Methods Colonoscopy reports about any resected endoscopic lesions were reviewed and subjected to histological diagnosis from 2005 to 2014. Then, serrated lesions were evaluated based on morphological characterization, location, size, occurrence of synchronous lesions, and the patient's history of colorectal cancer and polyps. Results A total of 2126 colonoscopy examination reports were reviewed, and 3494 lesions were analyzed. On histopathological examination, 1089 (31.2%) were classified as hyperplastic polyps, 22 (0.6%) as sessile serrated adenomas, and 21 (0.6%) as traditional serrated adenomas. There was an increase in the number of cases of sessile and traditional serrated adenomas diagnosed after 2010. Before 2010, two cases of sessile serrated adenomas and seven cases of traditional serrated adenomas were diagnosed; after 2010, 20 cases of sessile serrated adenoma and 14 cases of traditional serrated adenomas were diagnosed. Conclusion There was an increase in the diagnosis of sessile serrated adenomas over the years, which can be attributed to better accuracy in colonoscopy and histological classification.
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32
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Zhou G, Peng K, Song Y, Yang W, Shu W, Yu T, Yu L, Lin M, Wei Q, Chen C, Yin L, Cong Y, Liu Z. CD177+ neutrophils suppress epithelial cell tumourigenesis in colitis-associated cancer and predict good prognosis in colorectal cancer. Carcinogenesis 2018; 39:272-282. [PMID: 29228136 DOI: 10.1093/carcin/bgx142] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 12/01/2017] [Indexed: 12/25/2022] Open
Abstract
Neutrophils are found to be infiltrated in tumour tissues of patients with colitis-associated cancer (CAC) and colorectal cancer (CRC), and CD177 is mainly expressed in neutrophils. In our study, expression of CD177 in tumour tissues from patients with CAC or CRC was analysed byquantitative real-time polymerase chain reaction, flow cytometry and immunohistochemistry. We recruited 378 patients with CRC, determined CD177 expression in tumours and examined its correlation with clinicopathological features. Moreover, CAC model was induced in wild-type and CD177-/- mice by azoxymethane/dextran sodium sulphate. CD177+ neutrophils were significantly increased in colon tumour tissues from patients with CRC or CAC compared with controls. Expression of CD177 mRNA and percentages of CD177+ neutrophils were also markedly increased in tumour tissues from CRC patients compared with controls. Patients with high density of CD177+ neutrophils had better overall survival and disease-free survival compared with controls. Multivariate analyses revealed that the density of CD177+ neutrophils was an independent factor in predicting overall survival and disease-free survival. Consistently, CD177 depletion aggravated azoxymethane/dextran sodium sulphate-induced CAC in mice. Expression of Ki67 and proliferating cell nuclear antigen was increased in tumour tissues from CD177-/- mice compared with wild-type counterparts. Moreover, CD177-/- neutrophils failed to migrate in response to fMLP[AU: Please expand fMLP, DN, TNM and HIF-1α.] stimulation compared with wild-type controls. Our data indicate that CD177+ neutrophils suppress epithelial cell tumourigenesis and act as an independent factor in predicting the prognosis in patients with CRC. CD177+ neutrophils may serve as a novel therapeutic target in the treatment and predict the prognosis of CAC and CRC.
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Affiliation(s)
- Guangxi Zhou
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Kangsheng Peng
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Yang Song
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Wenjing Yang
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Weigang Shu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Tianming Yu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Lin Yu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Moubin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai, China
| | - Qing Wei
- Department of Pathology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Chunqiu Chen
- Department of General Surgery, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Lu Yin
- Department of General Surgery, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Yingzi Cong
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
| | - Zhanju Liu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
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Yoon JY, Cha JM, Shin JE, Kim KO, Yang HJ, Kim HG, Cho YS, Boo SJ, Lee J, Jung Y, Lee HJ, Koo HS, Joo YE. An Adjusted Level of Adenoma Detection Rate is Necessary for Adults Below 50 Years Old. J Clin Gastroenterol 2018; 52:703-708. [PMID: 28787362 DOI: 10.1097/mcg.0000000000000901] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Although adenoma prevalence is lower in younger people compared with screening-aged adults 50 years old and above, there is no adjustment recommendation for the target adenoma detection rate (ADR) in young people. Herein, we estimated a different target ADR for adults below 50 years old based on screening colonoscopy findings. MATERIALS AND METHODS Asymptomatic, average-risk adults below 50 years old who underwent screening colonoscopy were enrolled at 12 endoscopy centers in Korea between February 2006 and March 2012. Screening colonoscopies were stratified into low or high ADR groups with ADR levels of 20% and 25%, respectively. RESULTS The ADRs from 12 endoscopy centers ranged from 12.1% to 43.8% (median ADR, 24.1%) based on 5272 young adults receiving screening colonoscopies. Using 20% as an ADR level, the risks for metachronous adenoma and advanced adenoma were significantly higher in the low ADR group than the high ADR group (35.4% vs. 25.7%, P<0.001; 8.3% vs. 3.7%, P=0.001, respectively). However, using ADR level of 25%, the risk for metachronous neoplasia was similar in the high and low ADR groups in young adults according to screening colonoscopy. In subgroup analysis, similar findings were found in males, but not in females. CONCLUSIONS Optimal target ADR may be different between younger and older populations, and the adoption of a 20% target ADR could be used as a performance indicator for young populations.
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Affiliation(s)
- Jin Young Yoon
- Department of Internal Medicine, Kyung Hee University School of Medicine
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University School of Medicine
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu
| | - Hyo-Joon Yang
- Department of Internal Medicine, Kangbuk Samsung Hospital
| | - Hyun Gun Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine
| | - Young-Seok Cho
- Department of Internal Medicine, Catholic University College of Medicine
| | - Sun-Jin Boo
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju
| | - Jun Lee
- Department of Internal Medicine, Chosun University College of Medicine
| | - Yunho Jung
- Department of Internal Medicine, Soonchunhyang University College of Medicine
| | - Hyun Jung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul
| | - Hoon Sup Koo
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Young-Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju
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Kim SY, Kim TI. Serrated neoplasia pathway as an alternative route of colorectal cancer carcinogenesis. Intest Res 2018; 16:358-365. [PMID: 30090034 PMCID: PMC6077295 DOI: 10.5217/ir.2018.16.3.358] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 01/10/2023] Open
Abstract
In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes. With increasing information of the morphologic and molecular features of serrated lesions, one major challenge is how to reflect this knowledge in clinical practice, such as pathologic and endoscopic diagnosis, and guidelines for treatment and surveillance.
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Affiliation(s)
- Soon Young Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Pyo JH, Ha SY, Hong SN, Chang DK, Son HJ, Kim KM, Kim H, Kim K, Kim JE, Choi YH, Kim YH. Identification of risk factors for sessile and traditional serrated adenomas of the colon by using big data analysis. J Gastroenterol Hepatol 2018; 33:1039-1046. [PMID: 29087626 DOI: 10.1111/jgh.14035] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/23/2017] [Accepted: 10/24/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Little is known about the risk factors associated with serrated polyps, because the early studies, which occurred before the new World Health Organization classification was introduced, included mixtures of serrated polyps. This study aimed to evaluate the risk factors associated with the presence of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) using big data analytics. METHODS Using a case-control design, we evaluated the risk factors associated with the presence of SSAs and TSAs. Subjects who underwent colonoscopies from 2002 to 2012 as part of the comprehensive health screening programs undertaken at the Samsung Medical Center, Korea, participated in this study. RESULTS Of the 48 677 individuals who underwent colonoscopies, 183 (0.4%) had SSAs and 212 (0.4%) had TSAs. The multivariate analysis determined that being aged ≥ 50 years (odds ratio [OR] 1.91, 95% confidential interval [CI] 1.27-2.90, P = 0.002) and a history of colorectal cancer among first-degree relatives (OR 3.14, 95% CI 1.57-6.27, P = 0.001) were significant risk factors associated with the presence of SSAs and that being aged ≥ 50 years (OR 2.61, 95% CI 1.79-3.80, P < 0.001), obesity (OR 1.63, 95% CI 1.12-2.36, P = 0.010), and a higher triglyceride level (OR 1.63, 95% CI 1.12-2.36, P = 0.010) were independent risk factors associated with the presence of TSAs. CONCLUSIONS We used big data analytics to determine the risk factors associated with the presence of specific polyp subgroups, and individuals who have these risk factors should be carefully scrutinized for the presence of SSAs or TSAs during screening colonoscopies.
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Affiliation(s)
- Jeung Hui Pyo
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Jung Son
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea.,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyeseung Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Jee Eun Kim
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea
| | - Yoon-Ho Choi
- Center for Health Promotion, Samsung Medical Center, Seoul, Korea.,Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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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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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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Detection rate and proximal shift tendency of adenomas and serrated polyps: a retrospective study of 62,560 colonoscopies. Int J Colorectal Dis 2018; 33:131-139. [PMID: 29282495 DOI: 10.1007/s00384-017-2951-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/14/2017] [Indexed: 02/04/2023]
Abstract
PURPOSE The purpose of this study is to estimate the detection rates of adenomas and serrated polyps and to identify proximalization and associate risk factors in patients from Southern China. METHODS Consecutive patients undergoing colonoscopy from 2004 to 2013 in Guangzhou were included. The proportions of proximal adenomas to advanced adenomas and serrated polyps were compared and potential predictors were evaluated. RESULTS Colonoscopies (n = 62,560) were performed, and 11,427 patients were diagnosed with polyps. Detection rates for adenomas, hyperplastic polyps, and serrated adenomas were 12.0, 2.5, and 0.2 patients per 100 colonoscopies. When comparing the 1st (2004-2008) to the 2nd period (2009-2013), adenoma and serrated polyp detection in proximal and distal colon both increased significantly (proximal colon [adenoma 3.9 vs. 6.1 patients/100 colonoscopies, P < 0.001; serrated polyp 0.4 vs. 1.1 patients/100 colonoscopies, P < 0.001]; distal colon [adenoma 6.6 vs. 7.2 patients/100 colonoscopies, P = 0.003; serrated polyp 1.2 vs. 2.4 patients/100 colonoscopies, P < 0.001]). Advanced adenoma detection increased over these two periods only in proximal colon (1st vs. 2nd period: 1.5 vs. 2.4 patients/100 colonoscopies, P < 0.001), not the distal colon (P = 0.114). Multivariate analyses showed that diagnostic period was an independent predictor for adenoma proximalization (OR = 1.36, 95% CI 1.25-1.48, P < 0.001), but not for advanced adenomas (P = 0.117) or serrated polyps (P = 0.928). CONCLUSIONS Adenomas and serrated polyps were increasingly detected throughout the colon, whereas advanced adenomas were only in proximal colon. A proximal shift tendency detected by colonoscopy was observed for adenomas, but not advanced adenomas or serrated polyps, in Southern China. The screening for proximal polyps should be emphasized and colonoscopy might be a preferred initial screening tool.
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Park SJ, Yoon H, Jung IS, Shin CM, Park YS, Kim NY, Lee DH. Clinical outcomes of surveillance colonoscopy for patients with sessile serrated adenoma. Intest Res 2018; 16:134-141. [PMID: 29422808 PMCID: PMC5797260 DOI: 10.5217/ir.2018.16.1.134] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 05/03/2017] [Accepted: 05/07/2017] [Indexed: 01/09/2023] Open
Abstract
Background/Aims Sessile serrated adenomas (SSAs) are known to be precursors of colorectal cancer (CRC). The proper interval of follow-up colonoscopy for SSAs is still being debated. We sought to determine the proper interval of colonoscopy surveillance in patients diagnosed with SSAs in South Korea. Methods We retrospectively reviewed the medical records of patients diagnosed with SSAs who received 1 or more follow-up colonoscopies. The information reviewed included patient baseline characteristics, SSA characteristics, and colonoscopy information. Results From January 2007 to December 2011, 152 SSAs and 8 synchronous adenocarcinomas were identified in 138 patients. The mean age of the patients was 62.2 years and 60.1% patients were men. SSAs were located in the right colon (i.e., from the cecum to the hepatic flexure) in 68.4% patients. At the first follow-up, 27 SSAs were identified in 138 patients (right colon, 66.7%). At the second follow-up, 6 SSAs were identified in 65 patients (right colon, 66.7%). At the 3rd and 4th follow-up, 21 and 11 patients underwent colonoscopy, respectively, and no SSAs were detected. The total mean follow-up duration was 33.9 months. The mean size of SSAs was 8.1±5.0 mm. SSAs were most commonly found in the right colon (126/185, 68.1%). During annual follow-up colonoscopy surveillance, no cancer was detected. Conclusions Annual colonoscopy surveillance is not necessary for identifying new CRCs in all patients diagnosed with SSAs. In addition, the right colon should be examined more carefully because SSAs occur more frequently in the right colon during initial and follow-up colonoscopies.
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Affiliation(s)
- Sung Jae Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - In Sub Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Na Young Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Tamoto A, Yashima K, Hosoda K, Yamamoto S, Kawata S, Ikebuchi Y, Matsumoto K, Kawaguchi K, Harada K, Murawaki Y, Isomoto H. Protein expression of Fragile Histidine Triad and cyclooxgenase-2 in serrated neoplasia of the colorectum. Oncol Lett 2017; 14:3683-3688. [PMID: 28927131 PMCID: PMC5587971 DOI: 10.3892/ol.2017.6634] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 03/09/2017] [Indexed: 12/20/2022] Open
Abstract
The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma (CRC). However, the mechanism triggered by the serrated pathway remains unclear. Therefore, to clarify the molecular and clinicopathological characteristics of the serrated tumorigenic pathway, immunohistochemistry was used to examine the expression of Fragile Histidine Triad (FHIT), cyclooxygenase-2 (COX-2), MutL homolog 1 (MLH1), MutS protein homolog 2 (MSH2) and P53 in endoscopically resected samples of 62 serrated polyps. These samples included 20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs), 26 sessile serrated adenoma/polyps (SSA/Ps), 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure CRCs without any adenoma component (EPCs). FHIT expression was markedly reduced or absent in 50% of TSA samples, 92.3% of SSA/Ps and 44% of EPCs, but only rarely in HPs, non-serrated adenomas and CIAs. COX-2 expression was more common in non-serrated adenomas compared with in serrated polyps, and was present in 25 and 3.2% of the cases respectively (P<0.01). Furthermore, COX-2 expression was more frequent in CIAs (60%) compared with in EPCs (22.2%; P<0.05). The incidence of negative COX-2 expression was higher in FHIT-negative SSA/Ps compared with in FHIT-positive SSA/Ps (P=0.08). A total of 16.7% of EPC samples and 11.5% of SSA/Ps demonstrated a loss of MLH1/MSH2 expression, but none of the other tumor types did. P53 overexpression was significantly increased in EPC (77.8%) and CIA (60%) samples compared with in HP (0%), TSA (6.6%), SSA/P (0%) and non-serrated adenoma (10%) samples (P<0.01). These findings demonstrated that there are different expression patterns between the serrated pathway and ACS, indicating that aberrant FHIT and inhibited COX-2 expression may be associated with serrated tumorigenesis. In addition, this data indicated that EPC may contain tumors derived from the serrated pathway as well as ACS.
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Affiliation(s)
- Akihiro Tamoto
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Kazuo Yashima
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Kohei Hosoda
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Sohei Yamamoto
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Soichiro Kawata
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Yuichiro Ikebuchi
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Kazuya Matsumoto
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Koichiro Kawaguchi
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Kenichi Harada
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Yoshikazu Murawaki
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
| | - Hajime Isomoto
- Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
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O'Connell B, Hafiz N, Crockett S. The Serrated Polyp Pathway: Is It Time to Alter Surveillance Guidelines? Curr Gastroenterol Rep 2017; 19:52. [PMID: 28853002 DOI: 10.1007/s11894-017-0588-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW In this manuscript, we review current surveillance guidelines for serrated polyps (SPs) and discuss how recent studies inform the selection of appropriate surveillance intervals for patients with SPs. RECENT FINDINGS Large and/or proximal SPs, particularly sessile serrated polyps (SSPs), are associated with increased risk of both synchronous and metachronous neoplasia, including advanced adenomas and colorectal cancer (CRC). Persons harboring multiple SSPs or dysplastic SSPs are at the highest risk. Moreover, a high percentage of large and/or proximal SPs are reclassified as SSPs when read by trained gastrointestinal pathologists, even if they were originally reported as hyperplastic polyps. These findings support the adoption of surveillance guidelines that prescribe closer surveillance of large and/or proximal SPs, regardless of subtype. SSPs remain a challenge to reliably identify, resect, and diagnose via histology. The increased risk of future neoplasia in patients with SSPs is likely driven by a combination of underdetection, inadequate removal, misclassification, and biology. Until further evidence emerges, we support guidelines that recommend close surveillance of patients with a history of large and/or proximal SPs and SSPs specifically in order to mitigate the threat of interval CRC.
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Affiliation(s)
- Brendon O'Connell
- Department of Medicine, University of North Carolina School of Medicine, CB 7080, Chapel Hill, NC, 27599, USA
| | - Nazar Hafiz
- Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Seth Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
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Epidemiology and risk factors of colorectal polyps. Best Pract Res Clin Gastroenterol 2017; 31:419-424. [PMID: 28842051 DOI: 10.1016/j.bpg.2017.06.004] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 06/07/2017] [Accepted: 06/25/2017] [Indexed: 02/06/2023]
Abstract
The lifetime risk of colorectal cancer (CRC) in the Western world is around 5%. CRC commonly develops from precursor lesions termed polyps, classified as adenomatous or serrated polyps according to growth pattern. Despite the well-known connection between polyps and cancer, most polyps will never develop into CRC. For those that do, the time until CRC development is generally thought of as >10 years. This gives opportunity for interventional strategies to prevent transformation into cancer. This article aims to provide an overview of the epidemiology of and risk factors for colorectal polyps in the average risk population, and will encompass the effect of age, gender, ethnicity, smoking, obesity, alcohol, physical activity, NSAIDs and dietary factors on colorectal polyps.
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Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine 2017; 99:35-42. [PMID: 28689023 DOI: 10.1016/j.cyto.2017.06.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 06/01/2017] [Accepted: 06/20/2017] [Indexed: 12/20/2022]
Abstract
Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be further validated with larger sample size cohort to produce a panel of biomarkers for CRC and P patients. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.
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Thorlacius H, Takeuchi Y, Kanesaka T, Ljungberg O, Uedo N, Toth E. Serrated polyps - a concealed but prevalent precursor of colorectal cancer. Scand J Gastroenterol 2017; 52:654-661. [PMID: 28277895 DOI: 10.1080/00365521.2017.1298154] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 02/14/2017] [Accepted: 02/18/2017] [Indexed: 02/04/2023]
Abstract
Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1-2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.
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Affiliation(s)
- Henrik Thorlacius
- a Department of Clinical Sciences, Section, of Surgery , Skåne University Hospital, Lund University , Malmö , Sweden
| | - Yoji Takeuchi
- b Department of Gastrointestinal Oncology , Osaka Medical Center for Cancer and Cardiovascular Diseases , Osaka , Japan
| | - Takashi Kanesaka
- b Department of Gastrointestinal Oncology , Osaka Medical Center for Cancer and Cardiovascular Diseases , Osaka , Japan
| | - Otto Ljungberg
- c Department of Clinical Sciences, Section, of Gastroenterology , Skåne University Hospital, Lund University , Malmö , Sweden
| | - Noriya Uedo
- b Department of Gastrointestinal Oncology , Osaka Medical Center for Cancer and Cardiovascular Diseases , Osaka , Japan
| | - Ervin Toth
- d Department of Clinical Sciences, Section, of Pathology , Skåne University Hospital, Lund University , Malmö , Sweden
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Johdi NA, Ait-Tahar K, Sagap I, Jamal R. Molecular Signatures of Human Regulatory T Cells in Colorectal Cancer and Polyps. Front Immunol 2017; 8:620. [PMID: 28611777 PMCID: PMC5447675 DOI: 10.3389/fimmu.2017.00620] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 05/10/2017] [Indexed: 01/26/2023] Open
Abstract
Regulatory T cells (Tregs), a subset of CD4+ or CD8+ T cells, play a pivotal role in regulating immune homeostasis. An increase in Tregs was reported in many tumors to be associated with immune suppression and evasion in cancer patients. Despite the importance of Tregs, the molecular signatures that contributed to their pathophysiological relevance remain poorly understood and controversial. In this study, we explored the gene expression profiles in Tregs derived from patients with colorectal cancer [colorectal carcinoma (CRC), n = 15], colorectal polyps (P, n = 15), and in healthy volunteers (N, n = 15). Tregs were analyzed using CD4+CD25+CD127lowFoxP3+ antibody markers. Gene expression profiling analysis leads to the identification of 61 and 66 immune-related genes in Tregs derived from CRC and P patients, respectively, but not in N-derived Treg samples. Of these, 30 genes were differentially expressed both in CRC- and P-derived Tregs when compared to N-derived Tregs. Most of the identified genes were involved in cytokine/chemokine mediators of inflammation, chemokine receptor, lymphocyte activation, and T cell receptor (TCR) signaling pathways. This study highlights some of the molecular signatures that may affect Tregs’ expansion and possible suppression of function in cancer development. Our findings may provide a better understanding of the immunomodulatory nature of Tregs and could, therefore, open up new avenues in immunotherapy.
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Affiliation(s)
- Nor Adzimah Johdi
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Kamel Ait-Tahar
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Ismail Sagap
- Faculty of Medicine, Department of Surgery, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Rahman Jamal
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
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Herreros de Tejada A, González-Lois C, Santiago J. Serrated lesions and serrated polyposis syndrome. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:516-526. [PMID: 28530106 DOI: 10.17235/reed.2017.4065/2015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The serrated pathway has been shown to be an alternative colorectal carcinogenetic route potentially accounting for up to one third of all CRCs. Serrated lesions, particularly SSPs, have been a focus of research during the past few years. They have well-established histological and molecular characteristics that account for their potential carcinogenetic risk through the accumulation BRAF, KRAS and methylator profile (CpG) mutations. Their endoscopic identification and resection represent a challenge because of their specific characteristics, and the need for an adequate specimen for histological diagnosis. Knowledge of these lesions is key, as is the adoption of established criteria for their endoscopic description and histological diagnosis. SPS is the maximum expression of involvement by serrated lesions, is associated with increased risk for CRC, and requires attentive endoscopic follow-up, as well as family screening. While the exact etiopathogenic mechanism remains unknown, current research will likely provide us with appropriate answers in the not too distant future.
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Affiliation(s)
| | - Carmen González-Lois
- Anatomía Patológica, Hospital Universitario Puerta de Hierro Majadahonda, España
| | - José Santiago
- Digestivo, Hospital Universitario Puerta de Hierro Majadahonda, España
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Joshi BP, Dai Z, Gao Z, Lee JH, Ghimire N, Chen J, Prabhu A, Wamsteker EJ, Kwon RS, Elta GH, Stoffel EM, Pant A, Kaltenbach T, Soetikno RM, Appelman HD, Kuick R, Turgeon DK, Wang TD. Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy. Gastroenterology 2017; 152:1002-1013.e9. [PMID: 28012848 PMCID: PMC5771498 DOI: 10.1053/j.gastro.2016.12.009] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 12/13/2016] [Accepted: 12/13/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients. METHODS We used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 μmol/L and 22 patients were given 76.4 μmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hours after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy to identify suspicious regions. The fluorescently labeled peptide (76.4 μmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide to identify SSAs vs adenomas, hyperplastic polyps, and normal colonic mucosa in specimens obtained from the tissue bank at the University of Michigan. RESULTS We identified the peptide sequence KCCFPAQ and measured an apparent dissociation constant of Kd = 72 nM and an apparent association time constant of K = 0.174 min-1 (5.76 minutes). During fluorescence imaging of patients during endoscopy, regions of SSA had 2.43-fold higher mean fluorescence intensity than that for normal colonic mucosa. Fluorescence labeling distinguished SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. The peptide had no observed toxic effects in animals or patients. In the analysis of ex vivo specimens, peptide bound to SSAs had significantly higher mean fluorescence intensity than to hyperplastic polyps. CONCLUSIONS We have identified a fluorescently labeled peptide that has no observed toxic effects in animals or humans and can be used for wide-field imaging of lesions in the proximal colon. It distinguishes SSAs from normal colonic mucosa with 89% sensitivity and 92% specificity. This targeted imaging method might be used in early detection of premalignant serrated lesions during routine colonoscopies. ClinicalTrials.gov ID: NCT02156557.
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Affiliation(s)
- Bishnu P Joshi
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Zhenzhen Dai
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Zhenghong Gao
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Jeong Hoon Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Navin Ghimire
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Jing Chen
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Anoop Prabhu
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Erik J Wamsteker
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Richard S Kwon
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Grace H Elta
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Elena M Stoffel
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Asha Pant
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Tonya Kaltenbach
- Division of Gastroenterology, Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California
| | - Roy M Soetikno
- Division of Gastroenterology, Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California
| | - Henry D Appelman
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - Rork Kuick
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - D Kim Turgeon
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Thomas D Wang
- Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan.
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Cao HL, Chen X, Du SC, Song WJ, Wang WQ, Xu MQ, Wang SN, Piao MY, Cao XC, Wang BM. Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps. Chin Med J (Engl) 2017; 129:2427-2433. [PMID: 27748334 PMCID: PMC5072254 DOI: 10.4103/0366-6999.191759] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. Methods: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. Results: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010–11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). Conclusions: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN.
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Affiliation(s)
- Hai-Long Cao
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xue Chen
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Shao-Chun Du
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Wen-Jing Song
- Department of Pathology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Wei-Qiang Wang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Meng-Que Xu
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Si-Nan Wang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Mei-Yu Piao
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xiao-Cang Cao
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin 300052, China
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Abstract
Serrated polyps (SPs) of the colorectum pose a novel challenge to practicing gastroenterologists. Previously thought benign and unimportant, there is now compelling evidence that SPs are responsible for a significant percentage of incident colorectal cancer worldwide. In contrast to conventional adenomas, which tend to be slow growing and polypoid, SPs have unique features that undermine current screening and surveillance practices. For example, sessile serrated polyps (SSPs) are flat, predominately right-sided, and thought to have the potential for rapid growth. Moreover, SSPs are subject to wide variations in endoscopic detection and pathologic interpretation. Unfortunately, little is known about the natural history of SPs, and current guidelines are based largely on expert opinion. In this review, we outline the current taxonomy, epidemiology, and management of SPs with an emphasis on the clinical and public health impact of these lesions.
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Affiliation(s)
| | - Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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50
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Asadzadeh Aghdaei H, Nazemalhosseini Mojarad E, Ashtari S, Pourhoseingholi MA, Chaleshi V, Anaraki F, Haghazali M, Zali MR. Polyp detection rate and pathological features in patients undergoing a comprehensive colonoscopy screening. World J Gastrointest Pathophysiol 2017; 8:3-10. [PMID: 28251034 PMCID: PMC5311467 DOI: 10.4291/wjgp.v8.i1.3] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 10/29/2016] [Accepted: 12/09/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To identify the prevalence, and clinical and pathologic characteristic of colonic polyps among Iranian patients undergoing a comprehensive colonoscopy, and determine the polyp detection rate (PDR) and adenoma detection rate (ADR).
METHODS In this cross-sectional study, demographics and epidemiologic characteristics of 531 persons who underwent colonoscopies between 2014 and 2015 at Mehrad gastrointestinal clinic were determined. Demographics, indication for colonoscopy, colonoscopy findings, number of polyps, and histopathological characteristics of the polyps were examined for each person.
RESULTS Our sample included 295 (55.6%) women and 236 (44.4%) men, with a mean age of 50.25 ± 14.89 years. Overall PDR was 23.5% (125/531). ADR and colorectal cancer detection rate in this study were 12.8% and 1.5%, respectively. Polyps were detected more significantly frequently in men than in women (52.8% vs 47.2%, P < 0.05). Polyps can be seen in most patients after the age of 50. The average age of patients with cancer was significantly higher than that of patients with polyps (61.3 years vs 56.4 years, P < 0.05). The majority of the polyps were adenomatous. More than 50% of the polyps were found in the rectosigmoid part of the colon.
CONCLUSION The prevalence of polyps and adenomas in this study is less than that reported in the Western populations. In our patients, distal colon is more susceptible to developing polyps and cancer than proximal colon.
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