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Toyoshima N, Mizuguchi Y, Takamaru H, Nakamura K, Kakugawa Y, Sakamoto T, Shiroyama M, Kawagoe R, Tsuchiya K, Shinmura K, Ikematsu H, Inaba A, Minakata N, Hotta K, Imai K, Takada K, Ito S, Misawa M, Wakamura K, Kudo SE, Tamai N, Sumiyama K, Ito M, Uraoka T, Tomaru S, Matsuda T, Fujimoto A, Shibata T, Saito Y. The Efficacy of Texture and Color Enhancement Imaging Observation in the Detection of Colorectal Lesions: A Multicenter, Randomized Controlled Trial (deTXIon Study). Gastroenterology 2025:S0016-5085(25)00524-4. [PMID: 40113100 DOI: 10.1053/j.gastro.2025.03.007] [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: 10/09/2024] [Revised: 02/04/2025] [Accepted: 03/01/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND & AIMS Colonoscopy is the gold standard for detecting and resecting adenomas and early-stage cancers to reduce colorectal cancer (CRC) incidence and mortality rates. This study aimed to confirm the superiority of texture and color enhancement imaging (TXI) over white light imaging (WLI) in detecting colorectal lesions. METHODS This randomized controlled trial was conducted at 8 Japanese institutions between March 2023 and October 2023. Participants aged 40 to 80 years old scheduled for CRC screening and nonscreening purposes, such as postpolypectomy surveillance, positive fecal occult blood test results, and abdominal symptoms, were included. We used only the latest model colonoscopes and performed observations in each arm of the TXI model and WLI. The primary end point was the mean number of adenomas detected per procedure. Secondary end points included the adenoma detection rate, polyp detection rate, flat polyp detection rate, and adverse events. RESULTS A total of 956 patients were enrolled and randomized. After patients who did not meet the eligibility criteria were excluded, 451 and 445 patients were included in the TXI and WLI arms, respectively. The mean number of adenomas detected per procedure was 1.4 and 1.5 and the adenoma detection rate was 57.2% and 56.0% in TXI and WLI, respectively, and there were no statistically significant differences between 2 arms. The polyp detection rate and flat polyp detection rate were significantly higher in TXI than in WLI, which were 82.5% vs 74.4% (P = .003), and 76.5% vs 70.3% (P = .036), respectively. CONCLUSIONS This study did not demonstrate the superiority of TXI over WLI in detecting neoplastic lesions. However, TXI may be effective in detecting flat polyps. CLINICAL TRIAL REGISTRATION jRCT1032230089.
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Affiliation(s)
- Naoya Toyoshima
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | | | | | - Keiko Nakamura
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yasuo Kakugawa
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Taku Sakamoto
- Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
| | - Mamiko Shiroyama
- Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
| | - Ryosuke Kawagoe
- Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
| | - Kensuke Shinmura
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Hiroaki Ikematsu
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Atsushi Inaba
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Nobuhisa Minakata
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kazunori Takada
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masashi Misawa
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Kunihiko Wakamura
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Shin-Ei Kudo
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Naoto Tamai
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazuki Sumiyama
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Mamoru Ito
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Shota Tomaru
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Takahisa Matsuda
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Toho University, Tokyo, Japan
| | - Ai Fujimoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Toho University, Tokyo, Japan
| | - Taro Shibata
- Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
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Baile‐Maxía S, Mangas‐Sanjuan C, Sala‐Miquel N, Barquero C, Belda G, García‐del‐Castillo G, García‐Herola A, Penalva JC, Picó M, Poveda M, de‐Vera F, Zapater P, Jover R. Incidence, characteristics, and predictive factors of post-colonoscopy colorectal cancer. United European Gastroenterol J 2024; 12:309-318. [PMID: 38234220 PMCID: PMC11017761 DOI: 10.1002/ueg2.12512] [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: 08/21/2023] [Accepted: 10/27/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Post-colonoscopy colorectal cancer (PCCRC) is colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is found. OBJECTIVE As PCCRC has become an important quality indicator, we determined its rates, characteristics, and index colonoscopy-related predictive factors. METHODS We carried out a multicenter, observational, retrospective study between 2015 and 2018. Rates were calculated for PCCRC developing up to 10 years after colonoscopy. PCCRC was categorized according to the most plausible explanation using World Endoscopy Organization methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date, indication, endoscopist, and hospital. RESULTS One hundred seven PCCRC and 2508 detected CRC were diagnosed among 101,524 colonoscopy (0.1%), leading to rates of 0.4%, 2.2%, 3.1%, and 4.1% at 1, 3, 5, and 10 years, respectively. PCCRC was in right (42.4%), left (41.4%), and transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, and 11.2% stage IV. Twenty point three percent were classified as incomplete resection, 5.4% as unresected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. The median time from colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC. CONCLUSIONS In our population, 4.1% of CRC cases were PCCRC. Most of these lesions were in right colon and attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.
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Affiliation(s)
- Sandra Baile‐Maxía
- Gastroenterology DepartmentHospital General Universitario Dr. BalmisInstituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL)Departamento de Medicina Clínica, Universidad Miguel HernándezAlicanteSpain
| | - Carolina Mangas‐Sanjuan
- Gastroenterology DepartmentHospital General Universitario Dr. BalmisInstituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL)Departamento de Medicina Clínica, Universidad Miguel HernándezAlicanteSpain
| | - Noelia Sala‐Miquel
- Gastroenterology DepartmentHospital General Universitario Dr. BalmisInstituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL)Departamento de Medicina Clínica, Universidad Miguel HernándezAlicanteSpain
| | - Claudia Barquero
- Gastroenterology DepartmentHospital Universitario de TorreviejaTorreviejaSpain
| | - Germán Belda
- Gastroenterology DepartmentHospital Universitario Vega BajaOrihuelaSpain
| | | | | | | | - María‐Dolores Picó
- Gastroenterology DepartmentHospital General Universitario de ElcheElcheSpain
| | | | - Félix de‐Vera
- Gastroenterology DepartmentHospital General Universitario de EldaEldaSpain
| | - Pedro Zapater
- Clinical Pharmacology UnitHospital General Universitario Dr. BalmisInstituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL)Universidad Miguel HernándezIDIBECIBERehdAlicanteSpain
| | - Rodrigo Jover
- Gastroenterology DepartmentHospital General Universitario Dr. BalmisInstituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL)Departamento de Medicina Clínica, Universidad Miguel HernándezAlicanteSpain
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Brown I, Bettington M. Sporadic Polyps of the Colorectum. Gastroenterol Clin North Am 2024; 53:155-177. [PMID: 38280746 DOI: 10.1016/j.gtc.2023.10.002] [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: 01/29/2024]
Abstract
Colorectal polyps are common, and their diagnosis and classification represent a major component of gastrointestinal pathology practice. The majority of colorectal polyps represent precursors of either the chromosomal instability or serrated neoplasia pathways to colorectal carcinoma. Accurate reporting of these polyps has major implications for surveillance and thus for cancer prevention. In this review, we discuss the key histologic features of the major colorectal polyps with a particular emphasis on diagnostic pitfalls and areas of contention.
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Affiliation(s)
- Ian Brown
- Envoi Pathology, Brisbane; Pathology Queensland, Royal Brisbane and Women's Hospital Cnr Herston and Bowen Bridge Roads, Herston Qld 4006, Australia; University of Queensland, St Lucia, Qld 4072, Australia.
| | - Mark Bettington
- Envoi Pathology, Brisbane; University of Queensland, St Lucia, Qld 4072, Australia; Queensland Institute of Medical Research, 300 Herston Road, Herston QLD 4006, Australia
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McWhinney CD, Lahr RE, Rex DK. Frequency of serrated polyposis syndrome recognition by community endoscopists. Endosc Int Open 2023; 11:E888-E892. [PMID: 37810899 PMCID: PMC10558255 DOI: 10.1055/a-2157-4125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/25/2023] [Indexed: 10/10/2023] Open
Abstract
Background and study aims Some data indicate serrated polyposis syndrome (SPS) is underdiagnosed. We determined the frequency of SPS diagnosis by community endoscopists prior to referral to a tertiary center. Patients and methods We performed a retrospective analysis of a prospectively collected database of SPS patients at a tertiary academic hospital. There were 212 patients who were referred to our center for resection of one or more lesions detected at a prior colonoscopy and who had records available that allowed determination of whether SPS was diagnosed before referral. Results Only 25 of 212 patients (11.8%) had a diagnosis or suspicion of a polyposis syndrome prior to referral, and only 12 patients (5.7%) had a specific SPS diagnosis made prior to referral. Among 187 patients diagnosed at our center, 39 had sufficient serrated lesions removed and documented in outside records to meet SPS criteria prior to referral, but the diagnosis was not made by the referring physician despite adequate numbers of lesions resected. The remaining cases required lesions removed at our center to meet SPS diagnostic criteria. Limitations were a single center, single expert endoscopist. Conclusions SPS is the most common colorectal polyposis syndrome, but it remains underdiagnosed by community endoscopists. Underdiagnosis may contribute to post-colonoscopy colorectal cancer in patients with SPS.
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Affiliation(s)
- Connor D. McWhinney
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, United States
| | - Rachel E. Lahr
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, United States
| | - Douglas K. Rex
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, United States
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Yang K, Cao Y, Gurjao C, Liu Y, Guo CG, Lo CH, Zong X, Drew D, Geraghty C, Prezioso E, Moore M, Williams C, Riley T, Saul M, Ogino S, Giannakis M, Bass A, Schoen RE, Chan AT. Clinical and Genomic Characterization of Interval Colorectal Cancer in 3 Prospective Cohorts. Gastroenterology 2022; 163:1522-1530.e5. [PMID: 35970241 PMCID: PMC9691567 DOI: 10.1053/j.gastro.2022.08.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 08/05/2022] [Accepted: 08/08/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs. METHODS We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases. RESULTS A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21-1.78) for CRC-specific mortality and 1.27 (1.09-1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P > .05). CONCLUSION Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing.
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Affiliation(s)
- Keming Yang
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri
| | - Carino Gurjao
- Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Yang Liu
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Chuan-Guo Guo
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chun-Han Lo
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Xiaoyu Zong
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - David Drew
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Connor Geraghty
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Elizabeth Prezioso
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Matt Moore
- Information Management Services, Inc., Rockville, Maryland
| | - Craig Williams
- Information Management Services, Inc., Rockville, Maryland
| | - Tom Riley
- Information Management Services, Inc., Rockville, Maryland
| | - Melissa Saul
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Adam Bass
- Herbert Irving Comprehensive Cancer Center and Center for Precision Cancer Medicine, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York
| | - Robert E Schoen
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Division of Gastroenterology, Hepatology and Nutrition, and Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Sakamoto T, Ikematsu H, Tamai N, Mizuguchi Y, Takamaru H, Murano T, Shinmura K, Sasabe M, Furuhashi H, Sumiyama K, Saito Y. Detection of colorectal adenomas with texture and color enhancement imaging: Multicenter observational study. Dig Endosc 2022; 35:529-537. [PMID: 36398944 DOI: 10.1111/den.14480] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/17/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVES We aimed to evaluate the efficacy of texture and color enhancement imaging (TXI), which allows the acquisition of brighter images with enhanced color and surface structure in colorectal polyp detection compared to white light imaging. METHODS Patients who underwent colonoscopy with repeated ascending colon observation using TXI and white light imaging between August 2020 and January 2021 were identified in three institutions. The outcomes included the mean number of adenomas detected per procedure (MAP), adenoma detection rate (ADR), and ascending colonic adenoma miss rate (Ac-AMR). Logistic regression was used to determine the effects of the variables on the outcomes. RESULTS We included 1043 lesions from 470 patients in the analysis. The MAP, ADR, flat polyp detection rate, and Ac-AMR in TXI and white light imaging were 1.5% (95% confidence interval 1.3-1.6%) vs. 1.0% (0.9-1.1%), 58.2% (51.7-64.6%) vs. 46.8% (40.2-53.4%), 66.2% (59.8-72.2%) vs. 49.8% (43.2-56.4%), and 17.9% (12.1-25.2%) vs. 28.2% (20.0-37.6%), respectively. TXI, age, withdrawal time, and endoscopy type were identified as significant factors affecting the MAP and the ADR using multivariate regression analysis. CONCLUSIONS Our study indicates that TXI improve the detection of colorectal neoplastic lesions. However, prospective randomized trials are required to confirm these findings.
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Affiliation(s)
- Taku Sakamoto
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Ikematsu
- Division of Science and Technology for Endoscopy, National Cancer Center Hospital East, Chiba, Japan.,Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Naoto Tamai
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | | | | | - Tatsuro Murano
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Kensuke Shinmura
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Maasa Sasabe
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Hiroto Furuhashi
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazuki Sumiyama
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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van der Vlugt M, Carvalho B, Fliers J, Montazeri N, Rausch C, Grobbee EJ, Engeland MV, Spaander MCW, Meijer GA, Dekker E. Missed colorectal cancers in a fecal immunochemical test-based screening program: Molecular profiling of interval carcinomas. World J Gastrointest Oncol 2022; 14:2195-2207. [PMID: 36438700 PMCID: PMC9694267 DOI: 10.4251/wjgo.v14.i11.2195] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/06/2022] [Accepted: 10/03/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND For optimizing fecal immunochemical test (FIT)-based screening programs, reducing the rate of missed colorectal cancers (CRCs) by FIT (FIT-interval CRCs) is an important aspect. Knowledge of the molecular make-up of these missed lesions could facilitate more accurate detection of all (precursor) lesions.
AIM To compare the molecular make-up of FIT-interval CRCs to lesions that are detected by FIT [screen-detected CRCs (SD-CRCs)].
METHODS FIT-interval CRCs observed in a Dutch pilot-program of FIT-based screening were compared to a control group of SD-CRCs in a 1:2 ratio, resulting in 27 FIT-interval CRC and 54 SD-CRCs. Molecular analyses included microsatellite instability (MSI), CpG island methylator phenotype (CIMP), DNA sequence mutations and copy number alterations (CNAs).
RESULTS Although no significant differences were reached, FIT-interval CRCs were more often CIMP positive and MSI positive (33% CIMP in FIT-interval CRCs vs 21% in SD-CRCs (P = 0.274); 19% MSI in FIT-interval CRCs vs 12% in SD-CRCs (P = 0.469)), and showed more often serrated pathway associated features such as BRAF (30% vs 12%, P = 0.090) and PTEN (15% vs 2.4%, P = 0.063) mutations. APC mutations, a classic feature of the adenoma-carcinoma-sequence, were more abundant in SD-CRCs (68% vs 40% in FIT-interval CRCs P = 0.035). Regarding CNAs differences between the two groups; FIT-interval CRCs less often showed gains at the regions 8p11.22-q24.3 (P = 0.009), and more often gains at 20p13-p12.1 (P = 0.039).
CONCLUSION Serrated pathway associated molecular features seem to be more common in FIT-interval CRCs, while classic adenoma carcinoma pathway associated molecular features seem to be more common in SD-CRCs. This indicates that proximal serrated lesions may be overrepresented among FIT-interval CRCs.
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Affiliation(s)
- Manon van der Vlugt
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Beatriz Carvalho
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Joelle Fliers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Nahid Montazeri
- Biostatistics Unit, Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
| | - Christian Rausch
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Esmée J Grobbee
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam 3015 CN, Netherlands
| | - Manon van Engeland
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6202 AZ, Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam 3015 CN, Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam 1105 AZ, Netherlands
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Murakami T, Kamba E, Nomura K, Kurosawa T, Haga K, Fukushima H, Takeda T, Shibuya T, Yao T, Nagahara A. Linked color imaging improves visibility of colorectal serrated lesion by high color contrast to surrounding mucosa. Dig Endosc 2022; 34:1422-1432. [PMID: 35689542 DOI: 10.1111/den.14374] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 06/08/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVES This study aimed to objectively evaluate the efficacy of linked color imaging (LCI) in diagnosing colorectal serrated lesions by utilizing visibility scores and color differences. METHODS We examined 89 serrated lesions, including 36 hyperplastic polyps (HPs), 47 sessile serrated lesions (SSLs), and six traditional serrated adenomas (TSAs). Visibility changes were scored by six endoscopists as follows: 4, excellent; 3, good; 2, fair; and 1, poor. Furthermore, images obtained by white-light imaging (WLI) or LCI were assessed using the CIELAB color space in the lesion and adjacent mucosa. We calculated the mean color values (L*, a*, and b*) measured at five regions of interest of the sample lesion and surrounding mucosa and derived the color difference (ΔE*). RESULTS The visibility scores of both HPs and SSLs in LCI were significantly higher than that in WLI (HPs, 3.67/2.89, P < 0.001; SSLs, 3.07/2.36, P < 0.001). Furthermore, SSLs showed a significantly higher L* value and significantly lower a* and b* values in LCI than the adjacent mucosae (L*, 61.76/58.23, P = 0.016; a*, 14.91/17.58, P = 0.019; b*, 20.42/24.21, P = 0.007), while WLI produced no significant difference in any color value. A similar trend was apparent in HPs. In all serrated groups, LCI revealed significantly greater ΔE* values between the lesion and adjacent mucosa than WLI (HPs, 11.54/6.12; SSLs, 13.43/7.67; TSAs, 35.00/22.48). CONCLUSION Linked color imaging showed higher color contrast between serrated lesions and the surrounding mucosae compared with WLI, indicating improved visibility of colorectal serrated lesion using LCI.
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Affiliation(s)
- Takashi Murakami
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Eiji Kamba
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kei Nomura
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Taro Kurosawa
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Keiichi Haga
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hirofumi Fukushima
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tsutomu Takeda
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Yao
- Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Departments of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
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9
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Murakami T, Kurosawa T, Fukushima H, Shibuya T, Yao T, Nagahara A. Sessile serrated lesions: Clinicopathological characteristics, endoscopic diagnosis, and management. Dig Endosc 2022; 34:1096-1109. [PMID: 35352394 DOI: 10.1111/den.14273] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/30/2022] [Accepted: 02/13/2022] [Indexed: 02/08/2023]
Abstract
The 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System (5th edition) introduced the term "sessile serrated lesion" (SSL) to replace the term "sessile serrated adenoma/polyp" (SSA/P). SSLs are early precursor lesions in the serrated neoplasia pathway that result in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potential. The 2019 WHO classification noted that dysplasia arising in an SSL most likely is an advanced polyp, regardless of the morphologic grade of the dysplasia. Detecting SSLs with or without dysplasia is critical; however, detection of SSLs is challenging, and their identification by endoscopists and pathologists is inconsistent. Furthermore, indications for their endoscopic treatment have not been established. Moreover, SSLs are considered to contribute to the development of post-colonoscopy colorectal cancers. Herein, the clinicopathological and endoscopic characteristics of SSLs, including features determined using white light and image-enhanced endoscopy, therapeutic indications, therapeutic methods, and surveillance are reviewed based on the literature. This information may lead to more intensive research to improve detection, diagnosis, and rates of complete resection of these lesions and reduce post-colonoscopy colorectal cancer rates.
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Affiliation(s)
- Takashi Murakami
- Departments of 1Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Taro Kurosawa
- Departments of 1Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
- Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hirofumi Fukushima
- Departments of 1Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tomoyoshi Shibuya
- Departments of 1Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takashi Yao
- Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Departments of 1Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
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10
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Vemulapalli KC, Lahr RE, Rex DK. Most large colorectal polyps missed by gastroenterology fellows at colonoscopy are sessile serrated lesions. Endosc Int Open 2022; 10:E659-E663. [PMID: 35571477 PMCID: PMC9106434 DOI: 10.1055/a-1784-0959] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 12/03/2021] [Indexed: 02/02/2023] Open
Abstract
Background and study aims Data on adenoma and sessile serrated lesion (SSL) miss rates for gastroenterology fellows during colonoscopy are limited. We aimed to describe the miss rate of fellows based on a second examination by a colonoscopist with a high rate of detection. Patients and methods Second- and third-year gastroenterology fellows at a single, tertiary center performed initial examinations. A single experienced attending doctor then performed a complete examination of the colon. We recorded the size and pathology of all lesions found at both examinations and calculated the adenoma and SSL miss rates for fellows. Results Ten trainees performed 100 examinations. Miss rates for conventional adenomas and SSLs were 30.5 % and 85.7 %, respectively. Among pre-cancerous polyps ≥ 10 mm, 10 of 14 lesions missed were SSLs. Conclusions While conventional adenoma detection skills of gastroenterology fellows are acceptable, SSL detection is poor.
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Affiliation(s)
- Krishna C. Vemulapalli
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, United States
| | - Rachel E. Lahr
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, United States
| | - Douglas K. Rex
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, United States
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11
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Lam AY, Duloy AM, Keswani RN. Quality Indicators for the Detection and Removal of Colorectal Polyps and Interventions to Improve Them. Gastrointest Endosc Clin N Am 2022; 32:329-349. [PMID: 35361339 DOI: 10.1016/j.giec.2021.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Modifiable risk factors for postcolonoscopy colorectal cancer include suboptimal lesion detection (missed neoplasms) and inadequate lesion removal (incomplete polypectomy) during colonoscopy. Competent detection and removal of colorectal polyps are thus fundamental to ensuring adequate colonoscopy quality. Several well-researched quality metrics for polyp detection have been implemented into clinical practice, chief among these the adenoma detection rate. Less data are available on quality indicators for polyp removal, which currently include complete resection rates and skills assessment tools. This review summarizes the available literature on quality indicators for the detection and removal of colorectal polyps, as well as interventions to improve them.
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Affiliation(s)
- Angela Y Lam
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, 2350 Geary Boulevard, San Francisco, CA 94115, USA
| | - Anna M Duloy
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Center, 1635 Aurora Court, Aurora, CO 80045, USA
| | - Rajesh N Keswani
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 North Street, Clair, Suite 1400, Chicago, IL 60611, USA.
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12
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Dawsey SP, Vacek PM, Ganguly EK. Patient and Endoscopic Characteristics of Postcolonoscopy Colon Cancer-A Case-control Study. GASTRO HEP ADVANCES 2022; 1:277-286. [PMID: 39131672 PMCID: PMC11307737 DOI: 10.1016/j.gastha.2022.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 01/07/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Colonoscopy is imperfect for colorectal cancer (CRC) prevention. Postcolonoscopy CRC (PCCRC) is defined as CRC detected after a screening or surveillance colonoscopy. PCCRCs can be divided into noninterval CRC and interval CRC. We performed a case-control study to identify risk factors for PCCRCs and to compare risks between noninterval and interval PCCRCs. Methods We designed a retrospective case-control study. Using a Vermont tumor registry data set, we identified all PCCRCs diagnosed at our medical center from January 2012 to September 2017. Cases were matched 1:3 with controls of the same age, sex, and index colonoscopy date. Results Fifty-four PCCRCs were matched with 162 controls and divided into noninterval (N = 27) and interval (N = 27) subsets. Overall PCCRC risk and noninterval PCCRC risk were significantly associated with history of polyps (odds ratio [OR] PCCRC = 2.71, OR noninterval = 4.41), sessile serrated polyps (OR PCCRC = 3.94, OR noninterval = 5.79), and high-risk adenoma (HRA) (OR PCCRC = 6.58, OR noninterval = 16.46) and with the index colonoscopy having a large polyp (OR PCCRC = 4.45, OR noninterval = 10.46) or having an HRA (OR PCCRC = 3.68, OR noninterval = 8.04). PCCRC risk and interval PCCRC risk were significantly associated with follow-up recommendations that did not correlate with American Gastroenterological Association surveillance guidelines (OR PCCRC = 3.30, OR interval = 4.85). Approximately 30% of PCCRCs could be attributed to endoscopic quality. Conclusion Overall PCCRC risk and noninterval PCCRC risk were significantly associated with traditional CRC risk factors including precancerous polyps and HRA on the index colonoscopy. Interval PCCRC was not associated with these risk factors. Many PCCRCs can be attributed to endoscopic quality, and nonadherence to CRC surveillance guidelines may be a novel risk factor.
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Affiliation(s)
- Sonja P. Dawsey
- Division of Gastroenterology and Hepatology, University of Vermont Medical Center, Burlington, Vermont
| | - Pamela M. Vacek
- Department of Medical Biostatistics, University of Vermont, Burlington, Vermont
| | - Eric K. Ganguly
- Division of Gastroenterology and Hepatology, University of Vermont Medical Center, Burlington, Vermont
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Lamba M, Brown I, Bettington M, Ryan K, Hanigan K, Lasenby K, Dixon A, Grimpen F, Gan C, Tutticci N, Appleyard M, Leggett B. Clinicopathological Correlates of Dysplastic Sessile Serrated Lesion: A Prospective Cohort Study With a High Detection Rate. GASTRO HEP ADVANCES 2022; 1:313-320. [PMID: 39131677 PMCID: PMC11308794 DOI: 10.1016/j.gastha.2021.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/27/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims Sessile serrated lesions (SSLs) develop colorectal cancer (CRC), through a critical intermediary stage of SSL with dysplasia (SSLd). In this prospective observational study, we aimed to assess clinicopathological correlates of SSLd in the setting of a high lesion-detection rate. Methods Patients diagnosed with SSL and SSLd from February 2018 until January 2020 were prospectively recruited, and SSLd specimens were re-evaluated by 2 expert pathologists in a blinded manner. Associations were analyzed using multivariate logistic regression models. Results A total of 6425 patients underwent 7423 colonoscopies, and 2671 SSLs were resected from 1047 patients. The overall SSL detection rate per colonoscopy was 15.9%. The median age of patients with SSL was 54 years (interquartile range, 39-66), and 43.3% were male. After pathologist review, 24 SSLds were confirmed in 20 patients. The median size of SSLd was 8 mm (interquartile range, 5.75-15.25), and 13 of 24 SSLds were <10 mm in size. After multivariate analysis, older age (odds ratio = 1.07, 95% confidence interval = 1.03-1.1) and higher number of synchronous SSLs (odds ratio = 1.12, 95% confidence interval = 1.02-1.23) were associated with the presence of dysplasia. Patient sex and number and size of synchronous adenomas were not associated with the presence of SSLd. Seven of 20 patients with SSLd had synchronous or metachronous SSLd. Six of 20 patients with SSLd met the diagnostic criteria for serrated polyposis syndrome. Conclusion The overall SSL detection rate was 15.9%, and 0.9% of SSLs were dysplastic. Older age and higher number of synchronous SSL were risk factors for the presence of dysplasia in SSLs. Thirty percent of patients with SSLd had serrated polyposis syndrome, and 35% had multiple SSLd.
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Affiliation(s)
- Mehul Lamba
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Ian Brown
- Department of Pathology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- Envoi Specialists Pathologists, Brisbane, Queensland, Australia
| | - Mark Bettington
- Envoi Specialists Pathologists, Brisbane, Queensland, Australia
| | - Kimberley Ryan
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Katherine Hanigan
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Kay Lasenby
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Alicia Dixon
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Florian Grimpen
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Chun Gan
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Nicholas Tutticci
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Mark Appleyard
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Barbara Leggett
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
- The School of Medicine, University of Queensland, Brisbane, Australia
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14
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Oh CK, Lee BI, Lee SH, Kim SJ, Lee HH, Lim CH, Kim JS, Cho YK, Park JM, Cho YS, Lee IS, Choi MG. Circumferential submucosal incision prior to endoscopic mucosal resection versus conventional endoscopic mucosal resection for colorectal lesions with endoscopic features of sessile serrated lesions. Surg Endosc 2022; 36:2087-2095. [PMID: 33913030 DOI: 10.1007/s00464-021-08495-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND AND AIMS Sessile serrated lesions (SSLs) are more prone to incomplete resection than conventional adenomas. This study evaluated whether circumferential submucosal incision prior to endoscopic mucosal resection (CSI-EMR) can increase the rate of complete and en bloc resections of colorectal lesions with endoscopic features of SSL. METHODS Retrospective analyses and propensity score matching were performed for the resection of colorectal lesions ≥ 10 mm with endoscopic features of SSL. RESULTS After 1:1 ratio matching, 127 lesions in the CSI-EMR group and 127 in the EMR group were selected for analysis. The median size of the lesions was 15 mm (IQR 12-16) in both groups. There was no significant difference in either the complete resection rate or en bloc resection rate between CSI-EMR and EMR groups (96.9% vs. 92.9%, P = 0.155; 92.1% vs. 89.0%, P = 0.391). By contrast, the R0 resection rate was significantly higher in the CSI-EMR group than in the EMR group (89.8% vs. 59.8%, P < 0.001). The median procedure time was significantly longer in the CSI-EMR group than in the EMR group (6.28 min vs. 2.55 min, P < 0.001), whereas there was no significant difference between the two groups in the incidence of adverse events or recurrence rate. Multivariate analysis showed that CSI-EMR was the only factor significantly associated with R0 resection (P < 0.001). CONCLUSIONS For colorectal lesions with endoscopic features of SSL, CSI-EMR does not increase the complete or en bloc resection rate, but does increase the R0 resection rate. The procedure time is longer for CSI-EMR than EMR. The association of CSI-EMR with R0 resection and non-recurrence should be further evaluated.
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Affiliation(s)
- Chang Kyo Oh
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - Bo-In Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea.
| | - Sung Hak Lee
- Departments of Hospital Pathology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, Korea.
| | - Seung-Jun Kim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - Han Hee Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, 1021,Tongil Ro, Eunpyeong-gu, Seoul, Korea
| | - Jin Su Kim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, 1021,Tongil Ro, Eunpyeong-gu, Seoul, Korea
| | - Yu Kyung Cho
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - Jae Myung Park
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - Young-Seok Cho
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - In Seok Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
| | - Myung-Gyu Choi
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, Korea
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15
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Bogie RMM, le Clercq CMC, Voorham QJM, Cordes M, Sie D, Rausch C, van den Broek E, de Vries SDJ, van Grieken NCT, Riedl RG, Sastrowijoto P, Speel EJ, Vos R, Winkens B, van Engeland M, Ylstra B, Meijer GA, Masclee AAM, Carvalho B. Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study. Br J Cancer 2021; 126:865-873. [PMID: 34912077 DOI: 10.1038/s41416-021-01619-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/12/2021] [Accepted: 10/29/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). METHODS Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. RESULTS In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). CONCLUSION Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. CLINICAL TRIAL REGISTRATION NTR3093 in the Dutch trial register ( www.trialregister.nl ).
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Affiliation(s)
- Roel M M Bogie
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Chantal M C le Clercq
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Quirinus J M Voorham
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Martijn Cordes
- Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Daoud Sie
- Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Christian Rausch
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Evert van den Broek
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sara D J de Vries
- Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Robert G Riedl
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.,Department of Pathology, Zuyderland Medical Centre, Heerlen, The Netherlands
| | - Prapto Sastrowijoto
- Department of Pathology, Zuyderland Medical Centre, Heerlen, The Netherlands
| | - Ernst-Jan Speel
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Rein Vos
- Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Manon van Engeland
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Bauke Ylstra
- Amsterdam UMC, location VUmc, Department of Pathology, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Ad A M Masclee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
| | - Beatriz Carvalho
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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16
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Abstract
Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.
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Affiliation(s)
- Priyanka Kanth
- Division of Gastroenterology, University of Utah, Salt Lake City, UT, USA
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - John M Inadomi
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
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17
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Barros RA, Monteverde MJ, Dumonceau JM, Barros AS, Rainero GL, Barros RF, Jaroslavsky MJ, de Elizalde S. Cold snare polypectomy without submucosal injection: safety and efficacy in 615 large serrated lesions. Endosc Int Open 2021; 9:E1421-E1426. [PMID: 34466368 PMCID: PMC8382506 DOI: 10.1055/a-1517-4054] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 05/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background and study aim Cold resection is becoming the standard of care for the resection of nonpedunculated colon lesions up to 10 mm in diameter. Sessile serrated adenomas/polyps (SSA/Ps), including those ≥ 10 mm, present various characteristics that make them ideal candidates for cold snare polypectomy (CSP). Patients and methods A prospectively maintained database was searched retrospectively for consecutive patients with lesions ≥ 10 mm resected between March 2013 and March 2018. During that period, all SSA/P-appearing lesions were resected using CSP without submucosal injection, except for lesions with endoscopic suspicion of dysplasia or submucosal invasion. Patients with a pathological diagnosis of SSA/P were included in the analysis. Adverse events were recorded up to 21 days following colonoscopy. Results 615 SSA/Ps ≥ 10 mm were resected during 452 colonoscopy procedures in 379 patients (mean age 54.1 years; standard deviation [SD] 11.9 years). Mean polyp size was 13.7 (SD 5.2) mm; 122 lesions (19.8 %) were ≥ 20 mm and 479 lesions (77.9 %) underwent piecemeal resection. Immediate adverse events included persistent abdominal pain that resolved spontaneously within 2 hours in three patients (0.8 %; 95 % confidence interval [CI] 0.2 %-2.3 %). One patient with persistent intraprocedural bleeding was successfully treated with a hemostatic clip. No late adverse events were detected. Surveillance colonoscopy was performed in 293 patients (77.3 %) at 23.4 (SD 11.6) months following index colonoscopy; residual/recurrent lesions were diagnosed in 23 patients (7.8 %; 95 %CI 5.0 %-11.6 %). Conclusion CSP without submucosal injection appeared to be safe and effective for the resection of large SSA/Ps.
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Affiliation(s)
- Roberto Augusto Barros
- CEGA (Centro de Gastroenterología Ambulatoria, Ambulatory Gastroenterology Center), Campana, Buenos Aires, Argentina
| | - Maria Jose Monteverde
- CEGA (Centro de Gastroenterología Ambulatoria, Ambulatory Gastroenterology Center), Campana, Buenos Aires, Argentina
| | - Jean-Marc Dumonceau
- Gastroenterology Department, Charleroi University Hospitals, Charleroi, Belgium
| | - Augusto Sebastian Barros
- CEGA (Centro de Gastroenterología Ambulatoria, Ambulatory Gastroenterology Center), Campana, Buenos Aires, Argentina
| | - German Luis Rainero
- CEGA (Centro de Gastroenterología Ambulatoria, Ambulatory Gastroenterology Center), Campana, Buenos Aires, Argentina
| | - Roberto Federico Barros
- CEGA (Centro de Gastroenterología Ambulatoria, Ambulatory Gastroenterology Center), Campana, Buenos Aires, Argentina
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18
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Murakami T, Sakamoto N, Fukushima H, Shibuya T, Yao T, Nagahara A. Usefulness of the Japan narrow-band imaging expert team classification system for the diagnosis of sessile serrated lesion with dysplasia/carcinoma. Surg Endosc 2021; 35:4528-4538. [PMID: 32909209 DOI: 10.1007/s00464-020-07967-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 08/27/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. METHODS We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. RESULTS Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. CONCLUSIONS Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.
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Affiliation(s)
- Takashi Murakami
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Naoto Sakamoto
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hirofumi Fukushima
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Abstract
INTRODUCTION Some colorectal cancers (CRCs) may be missed during colonoscopies. We aimed to determine the clinicopathological, biological, and genomic characteristics of post-colonoscopy CRCs (PCCRCs). METHODS Of the 1,619 consecutive patients with 1,765 CRCs detected between 2008 and 2016, 63 patients with 67 PCCRCs, when colonoscopies were performed 6-60 months before diagnosis, were recruited. After excluding patients with inflammatory bowel disease, familial polyposis syndrome, CRCs that developed from diminutive adenomatous polyps, and recurrent CRCs after endoscopic resection, 32 patients with 34 PCCRCs were enrolled. The lesions' clinicopathological features, mismatch repair proteins (MMRs), and genomic alterations were investigated. RESULTS The overall PCCRC-5y rate, rate of intramucosal (Tis) lesions, and rate of T1 or more deeply invasive cancers were 3.7% (66/1,764), 3.9% (32/820), and 3.6% (34/944), respectively. Thirty-three patients' MMRs were investigated; 7 (21%) exhibited deficient MMRs (dMMRs), comprising 4 with T2 or more deeply invasive cancers and 5 whose lesions were in the proximal colon. Twenty-three tumors' genomic mutations were investigated; PIK3CA had mutated in 5 of 6 T2 or more deeply invasive cancers, of which, 4 were located in the proximal colon. Two patients with dMMRs and BRAF mutations had poor prognoses. Sixty-one percent (17/28) of the macroscopic type 0 lesions were superficial. All superficial Tis and T1 PCCRCs were detected <24 months after the negative colonoscopies. They were distributed throughout the colon and rectum. DISCUSSION PCCRCs may be invasive cancers in the proximal colon that exhibit dMMRs and/or PIK3CA mutations or missed early CRCs especially superficial lesions.
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20
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Lee JY, Lee JH. [Post-colonoscopy Colorectal Cancer: Causes and Prevention of Interval Colorectal Cancer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 75:314-321. [PMID: 32581202 DOI: 10.4166/kjg.2020.75.6.314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 06/08/2020] [Accepted: 06/18/2020] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in the worldwide. Colonoscopy is the gold standard for screening and surveillance of CRC. Removing adenomas by colonoscopy has lowered the incidence and mortality of CRC. However, colonoscopy is imperfect for detection of colorectal neoplasia. After a colonoscopy that is negative for malignancy, CRC can be diagnosed. These are termed as post-colonoscopy CRC (PCCRC). The proportion of PCCRC, among all CRC was reported to be 1.8% to 9.0%. It occurred 2.4 times more in the right colon than in the left colon. The causes of PCCRC are missed lesions, incomplete resection, and new lesions. Among these causes, missed lesion and incomplete resection are procedural factors and preventable. Therefore, it is necessary to improve the quality of colonoscopy to minimize the occurrence of PCCRC.
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Affiliation(s)
- Jong Yoon Lee
- Department of Gastroenterology, Dong-A University Hospital, Busan, Korea
| | - Jong Hoon Lee
- Department of Gastroenterology, Dong-A University Hospital, Busan, Korea
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21
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Ebner DW, Eckmann JD, Burger KN, Mahoney DW, Bering J, Kahn A, Rodriguez EA, Prichard DO, Wallace MB, Kane SV, Finney Rutten LJ, Gurudu SR, Kisiel JB. Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA. Clin Transl Gastroenterol 2021; 12:e00375. [PMID: 34140458 PMCID: PMC8216679 DOI: 10.14309/ctg.0000000000000375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/20/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.
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Affiliation(s)
- Derek W. Ebner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jason D. Eckmann
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kelli N. Burger
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Douglas W. Mahoney
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Jamie Bering
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Allon Kahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Eduardo A. Rodriguez
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - David O. Prichard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic Health System, La Crosse, Wisconsin, USA
| | - Michael B. Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Sunanda V. Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Suryakanth R. Gurudu
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - John B. Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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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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Bai J, Chen H, Bai X. Relationship between microsatellite status and immune microenvironment of colorectal cancer and its application to diagnosis and treatment. J Clin Lab Anal 2021; 35:e23810. [PMID: 33938589 PMCID: PMC8183910 DOI: 10.1002/jcla.23810] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 12/13/2022] Open
Abstract
Due to advances in understanding the immune microenvironment of colorectal cancer (CRC), microsatellite classification (dMMR/MSI-H and pMMR/MSS) has become a key biomarker for the diagnosis and treatment of CRC patients and therefore has important clinical value. Microsatellite status is associated with a variety of clinicopathological features and affects drug resistance and the prognosis of patients. CRC patients with different microsatellite statuses have different compositions and distributions of immune cells and cytokines within their tumor microenvironments (TMEs). Therefore, there is great interest in reversing or reshaping CRC TMEs to transform immune tolerant "cold" tumors into immune sensitive "hot" tumors. This requires a thorough understanding of differences in the immune microenvironments of MSI-H and MSS type tumors. This review focuses on the relationship between CRC microsatellite status and the immune microenvironment. It focuses on how this relationship has value for clinical application in diagnosis and treatment, as well as exploring the limitations of its current application.
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Affiliation(s)
- Junge Bai
- The Fourth Hospital of Harbin Medical UniversityHarbinChina
| | - Hongsheng Chen
- Department of General SurgeryThe Fourth Hospital of Harbin Medical UniversityHarbinChina
| | - Xuefeng Bai
- Department of Colorectal SurgeryHarbin Medical University Cancer HospitalHarbinChina
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24
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Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance. J Clin Med 2021; 10:jcm10112458. [PMID: 34206061 PMCID: PMC8198627 DOI: 10.3390/jcm10112458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 11/17/2022] Open
Abstract
Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs (n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p < 0.0005). The majority of incident cancers (21/28) were detected after previous colonoscopy without any pathological findings. On the molecular level, incident cancers presented with a significantly lower KRAS codon 12/13 (1/23, 4.3% vs. 11/21, 52%; p = 0.0005) and pathogenic TP53 mutation frequency (0/17, 0% vs. 7/21, 33.3%; p = 0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating APC mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. The proportion of MMR deficiency-related mutational events was significantly higher in incident compared to prevalent CRC (p = 0.018). In conclusion, our study identifies a set of features indicative of biological differences between incident and prevalent cancers in LS, which should further be monitored in prospective LS screening studies to guide towards optimized prevention protocols.
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25
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Ibáñez-Sanz G, Sanz-Pamplona R, Garcia M, on behalf of the MSIC-SC Research Group. Future Prospects of Colorectal Cancer Screening: Characterizing Interval Cancers. Cancers (Basel) 2021; 13:1328. [PMID: 33809520 PMCID: PMC8001713 DOI: 10.3390/cancers13061328] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/06/2021] [Accepted: 03/13/2021] [Indexed: 12/11/2022] Open
Abstract
Tumors that are not detected by screening tests are known as interval cancers and are diagnosed clinically after a negative result in the screening episode but before the next screening invitation. Clinical characteristics associated with interval colorectal cancers have been studied, but few molecular data are available that describe interval colorectal cancers. A better understanding of the clinical and biological characteristics associated with interval colorectal cancer may provide new insights into how to prevent this disease more effectively. This review aimed to summarize the current literature concerning interval colorectal cancer and its epidemiological, clinical, and molecular features.
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Affiliation(s)
- Gemma Ibáñez-Sanz
- Oncology Data Analytics Programme, Catalan Institute of Oncology, Hospitalet de Llobregat, 08907 Barcelona, Spain;
- Gastroenterology Department, Bellvitge University Hospital, Hospitalet de Llobregat, 08907 Barcelona, Spain
- Colorectal Cancer Research Group, ONCOBELL Programme, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, 08907 Barcelona, Spain
- CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Rebeca Sanz-Pamplona
- Oncology Data Analytics Programme, Catalan Institute of Oncology, Hospitalet de Llobregat, 08907 Barcelona, Spain;
- Colorectal Cancer Research Group, ONCOBELL Programme, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, 08907 Barcelona, Spain
- CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Montse Garcia
- CIBER Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Cancer Screening Unit, Prevention and Control Programme, Catalan Institute of Oncology, Hospitalet de Llobregat, 08907 Barcelona, Spain
- Early Detection of Cancer Research Group, EPIBELL Programme, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, 08907 Barcelona, Spain
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Abstract
BACKGROUND Screening for colorectal cancer (CRC) with colonoscopy has been credited for the majority of the decline in mortality over the past 40 years. However, colonoscopy is hampered by frequent interval cancers (ICs) occurring within 36 months after the last examination. Risk factors for IC imply that most misses are amenable to improved colonoscopic techniques. This study had two primary objectives: (1) to determine whether the proportion of persons with ICs has declined in association with improved approaches to the quality of colonoscopy and (2) to determine unrecognized causes for missed diagnoses. METHODS This is a retrospective, single-center study of persons with CRC having been diagnosed within 6-36 months since the most recent colonoscopy between 2006 and 2015. Participants, ages 50 and 89 years, were evaluated specifically for technical features and findings of the most recent colonoscopy. RESULTS Thirty-nine persons met the inclusion criteria for IC. Mean age was 69.3 years, range 50-86 years, women were 58%, races included 95% Caucasian, 2.5% Asian, and 2.5% African-American, and history of a first-degree relative with CRC was 26%. Symptoms led to the interval diagnosis in 83%, including iron-deficient anemia (38%), bleeding (25%), abdominal/pelvic pain (18%), and change in bowel habit (2.5%). Preexisting neoplasia was present in 72%. The CRC was located in the proximal colon in 51%. Late-stage disease was present in 45%. When compared to persons with an initial diagnosis of screen-detected late-onset CRC, differences were noted for older age, more women, more with a family history of CRC, and more with late-stage disease. The ratio of interval cancers to new cancers ranged between 6 and 11.5%. Findings indicating a "difficult examination" were observed in 14 cases (36%) compared to "easy or no difficulty" examinations in 25 (65%) cases. In a biennial analysis of IC rates between 2006 and 2015, the percentage of IC remained stable between 6 and 11.5%. CONCLUSIONS ICs have been stable constituting 6-11.5% of all CRCs. A "difficult examination" was often associated with IC, may be a risk factor for this problem, and may be an important clue warranting further study.
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27
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Dossa F, Sutradhar R, Saskin R, Hsieh E, Henry P, Richardson DP, Leake PA, Forbes SS, Paszat LF, Rabeneck L, Baxter NN. Clinical and endoscopist factors associated with post-colonoscopy colorectal cancer in a population-based sample. Colorectal Dis 2021; 23:635-645. [PMID: 33058360 DOI: 10.1111/codi.15400] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 09/06/2020] [Accepted: 09/29/2020] [Indexed: 02/08/2023]
Abstract
AIM Factors associated with verified post-colonoscopy colorectal cancers (PCCRC) have not been well defined and survival for these patients is not well described. We aimed to assess the association of patient, tumour and endoscopist characteristics with PCCRC. METHODS Using population-based data, we identified individuals diagnosed with CRC from 1 January 2000 to 31 December 2005 who underwent a colonoscopy within 3 years prior to diagnosis. Detected cancers were those diagnosed ≤6 months following colonoscopy; PCCRC were diagnosed >6 months to ≤3 years following colonoscopy. Post-colonoscopy and detected cancers were verified through chart review using a hospital-based simple random sampling frame. We used multivariable conditional logistic regression to determine the association of patient, tumour and endoscopist factors with PCCRC and compared overall survival using Cox proportional hazard models. RESULTS Using the random sampling frame, we identified 498 patients with PCCRC and 498 with detected CRC; we obtained records and confirmed 367 patients with PCCRC and 412 with detected cancers. In multivariable analysis, patient age (OR 1.01; 95% CI 1.00-1.03) and tumour location (distal vs. proximal OR 0.36; 95% CI 0.25-0.53) were associated with PCCRC; endoscopist quality measures were not significantly associated with PCCRC. We did not find significant differences in overall survival between PCCRC and detected cancers (hazard ratio 1.12; 95% CI 0.92-1.32). CONCLUSION Although endoscopic quality measures are important for CRC prevention, endoscopist factors were not associated with PCCRC. This study highlights the need for further research into the role of tumour biology in PCCRC development.
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Affiliation(s)
- Fahima Dossa
- Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.,Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Rinku Sutradhar
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Refik Saskin
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada
| | | | - Pauline Henry
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | | | - Pierre-Anthony Leake
- Department of Surgery, Radiology, Anaesthesia and Intensive Care, University of the West Indies, Kingston, Jamaica
| | - Shawn S Forbes
- Hamilton Health Sciences Centre, McMaster University, Hamilton, Canada
| | - Lawrence F Paszat
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Linda Rabeneck
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Cancer Care Ontario, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Nancy N Baxter
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada.,ICES, Toronto, Ontario, Canada.,Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.,Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada
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28
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ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol 2021; 116:458-479. [PMID: 33657038 DOI: 10.14309/ajg.0000000000001122] [Citation(s) in RCA: 430] [Impact Index Per Article: 107.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. CRC screening efforts are directed toward removal of adenomas and sessile serrated lesions and detection of early-stage CRC. The purpose of this article is to update the 2009 American College of Gastroenterology CRC screening guidelines. The guideline is framed around several key questions. We conducted a comprehensive literature search to include studies through October 2020. The inclusion criteria were studies of any design with men and women age 40 years and older. Detailed recommendations for CRC screening in average-risk individuals and those with a family history of CRC are discussed. We also provide recommendations on the role of aspirin for chemoprevention, quality indicators for colonoscopy, approaches to organized CRC screening and improving adherence to CRC screening. CRC screening must be optimized to allow effective and sustained reduction of CRC incidence and mortality. This can be accomplished by achieving high rates of adherence, quality monitoring and improvement, following evidence-based guidelines, and removing barriers through the spectrum of care from noninvasive screening tests to screening and diagnostic colonoscopy. The development of cost-effective, highly accurate, noninvasive modalities associated with improved overall adherence to the screening process is also a desirable goal.
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Marra G. An "expressionistic" look at serrated precancerous colorectal lesions. Diagn Pathol 2021; 16:4. [PMID: 33423702 PMCID: PMC7797135 DOI: 10.1186/s13000-020-01064-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 12/27/2020] [Indexed: 01/10/2023] Open
Abstract
Background Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated lesions (SSL), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as “serrated.” Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult. Methods We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies. Results SSLs could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSLs. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion. Conclusions Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes. Supplementary Information The online version contains supplementary material available at 10.1186/s13000-020-01064-1.
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Affiliation(s)
- Giancarlo Marra
- Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
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30
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Steel MJ, Bukhari H, Gentile L, Telford J, Schaeffer DF. Colorectal adenocarcinomas diagnosed following a negative faecal immunochemical test show high-risk pathological features in a colon screening programme. Histopathology 2020; 78:710-716. [PMID: 33037645 DOI: 10.1111/his.14278] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/06/2020] [Indexed: 12/30/2022]
Abstract
AIMS The faecal immunochemical test (FIT) is used every 2 years to screen average-risk British Columbians aged 50-74 years, with follow-up colonoscopy for positive results. Non-screen-detected colorectal adenocarcinomas are defined as those detected within 25 months following a negative FIT. We aimed to more clearly characterise these malignancies. METHODS AND RESULTS A medical chart and focused pathology review of colorectal malignancies from 926 individuals who completed FIT in the British Columbia Colon Screening Program in 2014, and whose pathology reports were available for review, was conducted. This cohort was divided into two groups: individuals with colorectal adenocarcinomas diagnosed following a positive FIT (screen-detected) and individuals with colorectal adenocarcinoma diagnosed within 25 months of a negative FIT (FIT-interval cancers). Rates of clinically relevant pathological parameters, as outlined in the American Joint Committee on Cancer (AJCC), 8th edition, were compared between the screen-detected and FIT-interval cancer groups. A total of 876 screen-detected and 50 FIT-interval cancers were identified. FIT-interval cancers exhibited higher rates of high-grade differentiation (including poorly differentiated and undifferentiated cases; P < 0.01) and aggressive histotype (signet ring cell and mucinous carcinomas; P < 0.01) than did screen-detected cancers after Bonferroni correction. Colorectal adenocarcinoma diagnosed after a negative FIT may therefore be associated with worse prognostic determinants than screen-detected cancers. CONCLUSION FIT-interval cancers are associated with high-risk pathological features; the possibility that more aggressive, fast-growing lesions which arise in the interval after truly negative FITs cannot be ruled out. Further study of a larger cohort of FIT-interval cancers controlling for interaction among the different pathologic parameters will be undertaken.
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Affiliation(s)
- Michael J Steel
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Hussam Bukhari
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Laura Gentile
- British Columbia Colon Screening Program, Vancouver, BC, Canada
| | - Jennifer Telford
- British Columbia Colon Screening Program, Vancouver, BC, Canada.,Division of Gastroenterology, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - David F Schaeffer
- Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Colon Screening Program, Vancouver, BC, Canada
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31
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Bleijenberg AGC, van Leerdam ME, Bargeman M, Koornstra JJ, van Herwaarden YJ, Spaander MCW, Sanduleanu S, Bastiaansen BAJ, Schoon EJ, van Lelyveld N, Dekker E, IJspeert JEG. Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: results from a prospective controlled trial. Gut 2020; 69:2150-2158. [PMID: 32139550 PMCID: PMC7677479 DOI: 10.1136/gutjnl-2019-319804] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 01/27/2020] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection. DESIGN An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme. RESULTS Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training. CONCLUSION A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs. TRIAL REGISTRATION NUMBER NCT03902899.
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Affiliation(s)
- Arne G C Bleijenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marloes Bargeman
- Department of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, The Netherlands
| | - Jan Jacob Koornstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Yasmijn J van Herwaarden
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Manon CW Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Silvia Sanduleanu
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Barbara A J Bastiaansen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Erik J Schoon
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands
| | - Niels van Lelyveld
- Department of Gastroenterology and Hepatology, Saint Antonius Hospital, Nieuwegein, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Joep E G IJspeert
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Nunoo-Mensah JW, Giordano P, Chung-Faye G. COVID-19: An Opportunity to Reimagine Colorectal Cancer Diagnostic Testing-A New Paradigm Shift. Clin Colorectal Cancer 2020; 19:227-230. [PMID: 32921580 PMCID: PMC7395219 DOI: 10.1016/j.clcc.2020.07.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 07/27/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Joseph W Nunoo-Mensah
- Department of Colorectal Surgery, King's College Hospital Foundation NHS Trust, London, UK; Cleveland Clinic London, London, UK.
| | - Pasquale Giordano
- Department of Colorectal Surgery, Whipps Cross University Hospital, London, UK
| | - Guy Chung-Faye
- Department of Gastroenterology, King's College Hospital Foundation NHS Trust, London, UK
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Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes: A Population-Based Case-Control Study. Am J Gastroenterol 2020; 115:2007-2016. [PMID: 32858564 DOI: 10.14309/ajg.0000000000000819] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC. METHODS This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC. RESULTS Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes. DISCUSSION Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.
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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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Guo F, Weigl K, Carr PR, Heisser T, Jansen L, Knebel P, Chang-Claude J, Hoffmeister M, Brenner H. Use of Polygenic Risk Scores to Select Screening Intervals After Negative Findings From Colonoscopy. Clin Gastroenterol Hepatol 2020; 18:2742-2751.e7. [PMID: 32376506 DOI: 10.1016/j.cgh.2020.04.077] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/22/2020] [Accepted: 04/24/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Polygenic risk scores (PRSs) could help to define starting ages for colorectal cancer (CRC) screening. However, the role of PRS in determining the length of screening interval after negative findings from colonoscopies is unclear. We aimed to evaluate CRC risk according to PRS and time since last negative colonoscopy. METHODS We collected data from 3827 cases and 2641 CRC-free controls in a population-based case-control study in Germany. We constructed a polygenic risk scoring system, based on 90 single-nucleotide polymorphisms, associated with risk of CRC in people of European descent. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. Multiple logistic regression models were used to assess CRC risk according to PRS and time since last negative colonoscopy. RESULTS Compared to individuals without colonoscopy in the low PRS category, a 42%-85% lower risk of CRC was observed for individuals who had a negative finding from colonoscopy within 10 years. Beyond 10 years after a negative finding from colonoscopy, significantly lower risk only persisted for the low and medium PRS groups, but not for the high PRS group. Adjusted odds ratios were 0.44 (95% CI, 0.29-0.68), 0.51 (95% CI, 0.34-0.77), and 0.85 (95% CI, 0.58-1.23) in the low, medium, and high PRS group, respectively. Within any time interval, risks were lower for distal than for proximal CRCs. CONCLUSIONS Based on findings from a population-based case-control study, the recommended 10-year screening interval for colonoscopy may not need to be shortened among people with high PRSs, but could potentially be prolonged for people with low and medium PRSs. Studies are needed to address personalized time intervals for repeat colonoscopies in average-risk screening cohorts.
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Affiliation(s)
- Feng Guo
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg
| | - Korbinian Weigl
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg
| | - Prudence Rose Carr
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg
| | - Thomas Heisser
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg
| | - Philip Knebel
- Department for General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg; Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
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Abstract
OBJECTIVES: Sessile serrated adenoma/polyps (SSA/Ps) contribute up to 30% of all colon cancers. There is considerable histological overlap between SSA/Ps and hyperplastic polyps. Inadequate consensus exists among pathologists, and no molecular biomarkers exist to differentiate these lesions with high accuracy. Lack of reliable diagnosis adversely affects clinical care. We previously defined a novel 7-gene panel by RNA sequencing that differentiates SSA/Ps from hyperplastic polyps. Here, we use the 7-gene panel as a molecular approach to differentiate SSA/Ps and HPs with higher sensitivity and specificity in a large sample set from a tertiary health care center. METHODS: Reverse transcription quantitative polymerase chain reaction of the 7-gene panel was performed on 223 formalin-fixed, paraffin-embedded serrated polyp and normal colon samples. We compare the sensitivity and specificity of the 7-gene panel with the BRAF and KRAS mutation incidence in differentiating SSA/Ps and HPs. We also evaluate the clinical data of patients with SSA/Ps showing high and low expression of the gene panel. RESULTS: The 7-gene RNA expression panel differentiates SSA/Ps and HPs with 89.2% sensitivity and 88.4% specificity. The gene panel outperforms BRAF mutation in identification of SSA/Ps. Clinical data suggest that expression of the 7-gene panel correlates with the development of SSA/Ps in the future. DISCUSSION: This study describes a novel 7-gene panel that identifies SSA/Ps with improved accuracy. Our data show that RNA markers of SSA/Ps advance the distinction of serrated lesions and contribute to the study of the serrated pathway to colon cancer.
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Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc 2020; 92:355-364.e5. [PMID: 32092289 DOI: 10.1016/j.gie.2020.02.016] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 02/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Although colonoscopy reduces colorectal cancer (CRC) risk, interval CRCs (iCRCs) still occur. We aimed to determine iCRC incidence, assess the relationship between adenoma detection rates (ADRs) and iCRC rates, and evaluate iCRC rates over time concomitant with initiation of an institutional colonoscopy quality improvement (QI) program. METHODS We performed a retrospective cohort study of patients who underwent colonoscopy at an academic medical center (January 2003 to December 2015). We identified iCRCs through our data warehouse and reviewed charts to confirm appropriateness for study inclusion. iCRC was defined as a cancer diagnosed 6 to 60 months and early iCRC as a cancer diagnosed 6 to 36 months after index colonoscopy. We measured the relationship between provider ADRs and iCRC rates and assessed iCRC rates over time with initiation of a QI program that started in 2010. RESULTS A total of 193,939 colonoscopies were performed over the study period. We identified 186 patients with iCRC. The overall iCRC rate was .12% and the early iCRC rate .06%. Average-risk patients undergoing colonoscopy by endoscopists in the highest ADR quartile (34%-52%) had a 4-fold lower iCRC risk (relative risk, .23; 95% confidence interval, .11-.48) than those undergoing colonoscopy by endoscopists in the lowest quartile (12%-21%). After QI program initiation, overall iCRC rates improved from .15% to .08% (P < .001) and early iCRC rates improved from .07% to .04% (P = .004). CONCLUSIONS We confirmed that iCRC rate is inversely correlated with provider ADR. ADRs increased and iCRC rates decreased over time, concomitant with a QI program focused on split-dose bowel preparation, quality metric measurement, provider education, and feedback. iCRC rate measurement should be considered a feasible, outcomes-driven institutional metric of colonoscopy quality.
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Toyoshima O, Nishizawa T, Yoshida S, Sekiba K, Kataoka Y, Hata K, Watanabe H, Tsuji Y, Koike K. Expert endoscopists with high adenoma detection rates frequently detect diminutive adenomas in proximal colon. Endosc Int Open 2020; 8:E775-E782. [PMID: 32490163 PMCID: PMC7247898 DOI: 10.1055/a-1136-9971] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/02/2020] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Adenoma detection rate (ADR) is an important quality indicator in colonoscopy, and improved ADR decreases the incidence of colorectal cancer. We investigated differences in polyp detection according to the endoscopist's ADR. Patients and methods We performed a propensity-score matching study using baseline patient characteristics of age, sex, body mass index, family history of colorectal cancer, smoking, drinking, indication for colonoscopy, bowel preparation, and colonoscope type. We compared polyp detection and colonoscopy procedures between patients who underwent colonoscopy by high-ADR endoscopists (high ADR group) and by low-ADR endoscopists (low ADR group). Results We matched 334 patients in the high ADR group with 334 in the low ADR group. The ADR was 44.0 % and 26.9 % for the high-ADR and low-ADR endoscopists, respectively. Proximal, nonprotruding, and diminutive adenomas were more frequently detected by high-ADR endoscopists than by low-ADR endoscopists (all P < 0.001); similarly, more high-risk adenomas were detected by high-ADR endoscopists ( P = 0.028). Furthermore, more sessile serrated polyps detected by high-ADR endoscopists ( P = 0.041). High-ADR endoscopists more frequently performed pancolonic chromoendoscopy ( P < 0.001). Conclusions Expert detectors often found nonprotruding and diminutive adenomas in the proximal colon along with increased detection rate of high-risk adenomas. Low-ADR endoscopists need to recognize the features of missed adenomas to improve their ADRs.
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Affiliation(s)
- Osamu Toyoshima
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan
| | - Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Mita Hospital, Tokyo, Japan
| | - Shuntaro Yoshida
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan
| | - Kazuma Sekiba
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan
| | - Yosuke Kataoka
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Sanraku Hospital, Chiyoda-ku, Japan
| | - Keisuke Hata
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Japan
| | | | - Yosuke Tsuji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan
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Mosley D, Su T, Murff HJ, Smalley WE, Ness RM, Zheng W, Shrubsole MJ. Meat intake, meat cooking methods, and meat-derived mutagen exposure and risk of sessile serrated lesions. Am J Clin Nutr 2020; 111:1244-1251. [PMID: 32077920 PMCID: PMC7266682 DOI: 10.1093/ajcn/nqaa030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 01/31/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Red and processed meat, recognized carcinogens, are risk factors for colorectal neoplasia, including polyps, the precursor for colorectal cancer. The mechanism is unclear. One possible explanation is the mutagenic activity of these foods, perhaps due to generation during cooking [e.g., heterocyclic amine (HCA) intake]. Few studies have evaluated meat intake and sessile serrated lesion (SSL) risk, a recently recognized precursor, and no study has evaluated meat cooking methods and meat-derived mutagens with SSL risk. OBJECTIVE We evaluated intakes of meat, meat cooking methods, and inferred meat mutagens with SSL risk and in comparison to risk of other polyps. METHODS Meat, well-done meat, and inferred meat mutagen intakes were evaluated. Polytomous logistic regression models were used to estimate ORs and 95% CIs among cases (556 hyperplastic polyp, 1753 adenoma, and 208 SSL) and controls (3804) in the large colonoscopy-based, case-control study, the Tennessee Colorectal Polyp Study. RESULTS The highest quartile intakes of red meat (OR: 2.38; 95% CI: 1.44, 3.93), processed meat (OR: 2.03; 95% CI: 1.30, 3.17), well-done red meat (OR: 2.19; 95% CI: 1.34, 3.60), and the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX; OR: 2.48; 95% CI: 1.49, 4.16) were associated with increased risk of SSLs in comparison to the lowest quartile intake. CONCLUSIONS High intakes of red and processed meats are strongly and especially associated with SSL risk and part of the association may be due to HCA intake. Future studies should evaluate other mechanism(s) and the potential for primary prevention.
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Affiliation(s)
- Dominique Mosley
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Spelman College, Atlanta, GA, USA
| | - Timothy Su
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Harvey J Murff
- Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
- Department of Medicine, Division of General Internal Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Walter E Smalley
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, TN, USA
- Gastroenterology Section, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Reid M Ness
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, TN, USA
- Gastroenterology Section, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Wei Zheng
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Martha J Shrubsole
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
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Guo F, De Brabander I, Francart J, Candeur M, Polus M, Van Eycken L, Brenner H. Benefits of switching from guaiac-based faecal occult blood to faecal immunochemical testing: experience from the Wallonia-Brussels colorectal cancer screening programme. Br J Cancer 2020; 122:1109-1117. [PMID: 32066910 PMCID: PMC7109124 DOI: 10.1038/s41416-020-0754-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 01/20/2020] [Accepted: 01/30/2020] [Indexed: 12/24/2022] Open
Abstract
Background Faecal immunochemical tests (FITs) have replaced guaiac-based faecal occult blood test (gFOBTs) in several colorectal cancer (CRC) screening programmes. We aimed to evaluate the benefits of this transition based on the Wallonia–Brussels-organised CRC screening programme. Methods A total of 1,569,868 individuals aged 50–74 years, who were invited to screening during 2009–2017, were studied by linking their screening records with insurance, pathology and cancer data in the Belgian Cancer Registry. We compared neoplasm detection rates and positive predictive values (PPVs) of gFOBT and FIT at 15 µg haemoglobin per gram cut-off in screen-naive individuals. We furthermore examined the incidence rates of interval cancer in gFOBT- and FIT-based screening programme. Results Advanced neoplasms were detected less frequently by gFOBT (0.8%) than by FIT (1.3%), with a difference of 0.5% (P < 0.01). PPVs were lower for gFOBT (15.1%) than for FIT (21.7%) for advanced neoplasms (difference 6.6%, P < 0.01). Compared to participants with negative gFOBT, those with negative FIT were 77% less likely to develop interval cancer (incidence rate ratio 0.23, 95% confidence interval 0.16–0.33). Conclusion Our study demonstrated that in an organised CRC screening programme, replacing gFOBT with FIT improved neoplasm detection rate and substantially reduced interval cancer incidence.
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Affiliation(s)
- Feng Guo
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | | | | | - Michel Candeur
- Community Reference Center for Cancer Screening (Wallonia), Mont-Saint-Guibert, Belgium
| | - Marc Polus
- Department of Gastroenterology, University Hospital of Liège, Liège, Belgium
| | | | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. .,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. .,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Abstract
BACKGROUND Colorectal sessile serrated lesion (SSL) with synchronous neoplasm or large size are linked to higher risk of cancer, but their characteristics are unclear. METHODS We prospectively included consecutive colorectal hyperplasic polyp and SSL collected at our institution from August 2011 to August 2012. The following data were collected and analyzed: age, gender, polyp site, aggregated polyp size, history of polyp, and synchronous neoplasm. RESULTS We collected 437 specimens including 353 (80.8%) hyperplasic polyp and 84 (19.2%) SSL. Compared with hyperplasic polyp, SSL was independently associated with proximal colon [odds ratio (OR) 3.61, P< 0.001], larger size (OR 3.98, P< 0.001), but not history of polyp, age or gender. Large SSL (≥1 vs <1 cm) was associated with polyp site (P= 0.035) and synchronous advanced adenoma and cancer (P< 0.001). SSL with synchronous adenoma and cancer were more likely found in males (OR 1.91, P= 0.001), elderly (OR 1.02, P= 0.033), and patients with the index polyp in proximal colon (OR 1.32, P= 0.022), but not related to history of adenoma and cancer. Moreover, synchronous adenoma, SSL and cancer were independently associated with male gender (OR 1.90, P< 0.001), but surprisingly not older age, histology of index polyp (SSL vs hyperplasic polyp), index-polyp site or history of adenoma and cancer. CONCLUSIONS This prospective study shows male gender is associated with both synchronous adenoma and cancer, and synchronous adenoma, SSL and cancer, while index polyp site is associated with synchronous adenoma and cancer.
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Traditional Serrated Adenomas on CT Colonography: International Multicenter Experience With This Rare Colorectal Neoplasm. AJR Am J Roentgenol 2020; 214:355-361. [DOI: 10.2214/ajr.19.21882] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Noreen F, Küng T, Tornillo L, Parker H, Silva M, Weis S, Marra G, Rad R, Truninger K, Schär P. DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways. Clin Epigenetics 2019; 11:196. [PMID: 31842975 PMCID: PMC6916434 DOI: 10.1186/s13148-019-0791-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 12/02/2019] [Indexed: 12/22/2022] Open
Abstract
Background Aberrations in DNA methylation are widespread in colon cancer (CC). Understanding origin and progression of DNA methylation aberrations is essential to develop effective preventive and therapeutic strategies. Here, we aimed to dissect CC subtype-specific methylation instability to understand underlying mechanisms and functions. Methods We have assessed genome-wide DNA methylation in the healthy normal colon mucosa (HNM), precursor lesions and CCs in a first comprehensive study to delineate epigenetic change along the process of colon carcinogenesis. Mechanistically, we used stable cell lines, genetically engineered mouse model of mutant BRAFV600E and molecular biology analysis to establish the role of BRAFV600E-mediated-TET inhibition in CpG-island methylator phenotype (CIMP) inititation. Results We identified two distinct patterns of CpG methylation instability, determined either by age–lifestyle (CC-neutral CpGs) or genetically (CIMP-CpGs). CC-neutral-CpGs showed age-dependent hypermethylation in HNM, all precursors, and CCs, while CIMP-CpGs showed hypermethylation specifically in sessile serrated adenomas/polyps (SSA/Ps) and CIMP-CCs. BRAFV600E-mutated CCs and precursors showed a significant downregulation of TET1 and TET2 DNA demethylases. Stable expression of BRAFV600E in nonCIMP CC cells and in a genetic mouse model was sufficient to repress TET1/TET2 and initiate hypermethylation at CIMP-CpGs, reversible by BRAFV600E inhibition. BRAFV600E-driven CIMP-CpG hypermethylation occurred at genes associated with established CC pathways, effecting functional changes otherwise achieved by genetic mutation in carcinogenesis. Conclusions Hence, while age–lifestyle-driven hypermethylation occurs generally in colon carcinogenesis, BRAFV600E-driven hypermethylation is specific for the “serrated” pathway. This knowledge will advance the use of epigenetic biomarkers to assess subgroup-specific CC risk and disease progression.
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Affiliation(s)
- Faiza Noreen
- Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland.,Swiss Institute of Bioinformatics, 4053, Basel, Switzerland
| | - Taya Küng
- Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland
| | - Luigi Tornillo
- Institute of Pathology, University Hospital Basel, 4056, Basel, Switzerland
| | - Hannah Parker
- Institute of Molecular Cancer Research, University of Zurich, 8057, Zurich, Switzerland
| | - Miguel Silva
- Department of Medicine II, Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany
| | - Stefan Weis
- Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland
| | - Giancarlo Marra
- Institute of Molecular Cancer Research, University of Zurich, 8057, Zurich, Switzerland
| | - Roland Rad
- Department of Medicine II, Klinikum Rechts der Isar, Technische Universität München, 81675, Munich, Germany
| | - Kaspar Truninger
- Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland. .,Gastroenterologie Oberaargau, CH-4900, Langenthal, Switzerland.
| | - Primo Schär
- Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058, Basel, Switzerland.
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Samadder NJ, Neklason D, Snow A, Samowitz W, Cessna MH, Rowe K, Sandhu I, Boucher K, Pappas L, Smith KR, Wong J, Curtin K, Provenzale D, Burt RW. Clinical and Molecular Features of Post-Colonoscopy Colorectal Cancers. Clin Gastroenterol Hepatol 2019; 17:2731-2739.e2. [PMID: 30930275 DOI: 10.1016/j.cgh.2019.02.040] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 02/15/2019] [Accepted: 02/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy). METHODS Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Archived specimens were retrieved and tested for microsatellite instability (MSI), CpG island methylation, and mutations in KRAS and BRAF. There were 2659 cases of CRC diagnosed within the study window; 6% of these (n = 159) were defined as PCCRCs; 84 of these cases had tissue available and were matched to 84 subjects with detected CRC. RESULTS Higher proportions of PCCRCs than detected CRCs formed in the proximal colon (64% vs 44%; P = .016) and were of an early stage (86% vs 69%; P = .040). MSI was observed in 32% of PCCRCs compared with 13% of detected CRCs (P = .005). The other molecular features were found in similar proportions of PCCRCs and detected CRCs. In a multivariable logistic regression, MSI (odds ratio, 4.20; 95% CI, 1.58-11.14) was associated with PCCRC. There was no difference in 5-year survival between patients with PCCRCs vs detected CRCs. CONCLUSION In this population-based cross-sectional study of incident CRC cases in Utah, we found PCCRCs to be more likely to arise in the proximal colon and demonstrate MSI, so PCCRCs and detected CRC appear to have different features or processes of tumorigenesis. Additional studies are needed to determine if post-colonoscopy cancers arise through a specific genetic pathway.
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Affiliation(s)
- N Jewel Samadder
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, Utah; Department of Medicine (Gastroenterology), Mayo Clinic, Phoenix, Arizona.
| | - Deb Neklason
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Genetic Epidemiology), University of Utah, Salt Lake City, Utah
| | - Angela Snow
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Wade Samowitz
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Pathology, University of Utah, Salt Lake City, Utah
| | - Melissa H Cessna
- Department of Pathology and Biorepository, Intermountain Healthcare, Salt Lake City, Utah
| | - Kerry Rowe
- Department of Medicine, Intermountain Healthcare, Salt Lake City, Utah
| | - Iqbal Sandhu
- Department of Bioinformatics, Intermountain Healthcare, Salt Lake City, Utah
| | - Kenneth Boucher
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Lisa Pappas
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Ken Robert Smith
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Jathine Wong
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Karen Curtin
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Genetic Epidemiology), University of Utah, Salt Lake City, Utah
| | - Dawn Provenzale
- Department of Medicine (Gastroenterology), Duke University, Durham, North Carolina; VA Cooperative Studies Program Epidemiology Center, Departments of Medicine (Gastroenterology) and Clinical Genomics, Mayo Clinic, Phoenix, Arizona
| | - Randall W Burt
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Gastroenterology), University of Utah, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah
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Buerger M, Kasper P, Allo G, Gillessen J, Schramm C. Ileal intubation is not associated with higher detection rate of right-sided conventional adenomas and serrated polyps compared to cecal intubation after adjustment for overall adenoma detection rate. BMC Gastroenterol 2019; 19:190. [PMID: 31730463 PMCID: PMC6858714 DOI: 10.1186/s12876-019-1111-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 11/07/2019] [Indexed: 12/24/2022] Open
Abstract
Background High cecal intubation rate (CIR) is associated with significant improved adenoma detection rate (ADR), however, self-reported CIR may be overestimated and inadequate documentation of cecal intubation is associated with a lower polyp detection rate compared to clear documentation. We aimed to investigate if ileal intubation may be associated with higher detection rates (DR) for right-sided conventional adenomas (cAD) and serrated polyps (SP) compared to cecal intubation in a large screening colonoscopy cohort. Material and methods Retrospective analysis of individuals ≥50 years with average risk for colorectal cancer (CRC) who underwent screening colonoscopy between 01/01/2012 and 14/12/2016 at a tertiary academic hospital and six community-based private practices. Exclusion criteria were conditions with increased risk for CRC (e.g. inflammatory bowel disease, history of CRC, hereditary cancer syndromes), previous colonoscopy at the same institution, and incomplete procedures. Right-sided colon was defined as caecum and ascending colon. Results 4.138 individuals were analysed (mean age 62 years, 52.1% female). DR for right-sided cADs and SPs were significantly higher after ileal compared to cecal intubation in univariate (12.5% vs. 6.8%, p < 0.001, and 6.3% vs. 3.3%, p < 0.001), but not in multivariate analysis (OR 1.025, 95%-CI 0.639–1.646, p = 0.918, and OR 0.937, 95%-CI 0.671–1.309, p = 0.704). DRs did not differ between ileal and cecal intubation for endoscopists with ADR ≥25 and < 25%, respectively. ADR ≥25% was significantly associated with ileal intubation (OR 21.862, 95%-CI 18.049–26.481, p < 0.001). Conclusion Ileal intubation may not provide any benefit over cecal intubation concerning the detection of cADs and SPs in the right-sided colon.
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Affiliation(s)
- Martin Buerger
- Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Philipp Kasper
- Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Gabriel Allo
- Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Johannes Gillessen
- Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany
| | - Christoph Schramm
- Department for Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, Kerpener Strasse 62, 50937, Cologne, Germany.
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Pai RK, Bettington M, Srivastava A, Rosty C. An update on the morphology and molecular pathology of serrated colorectal polyps and associated carcinomas. Mod Pathol 2019; 32:1390-1415. [PMID: 31028362 DOI: 10.1038/s41379-019-0280-2] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/28/2019] [Accepted: 03/29/2019] [Indexed: 02/08/2023]
Abstract
Our understanding of serrated colorectal polyps has increased dramatically over the past two decades and has led to a modern classification scheme for these lesions. Sessile serrated polyps with dysplasia represent the most clinically significant serrated polyp; however, the morphologic heterogeneity of dysplasia in sessile serrated polyps has only recently been recognized and correlated with MLH1 immunohistochemistry. Detailed morphologic analysis of traditional serrated adenomas has led to the recognition of flat and early forms of this polyp. Robust data on the risk of metachronous lesions in patients with serrated polyps are also beginning to emerge. This review will summarize our current understanding of serrated polyps and associated carcinomas with a focus on diagnostic criteria, morphologic heterogeneity, molecular findings, and natural history. Controversial issues in the diagnosis and classification of these polyps are also discussed.
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Affiliation(s)
- Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
| | - Mark Bettington
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.,Envoi Specialist Pathologists, Brisbane, QLD, 4059, Australia.,The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
| | - Amitabh Srivastava
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA
| | - Christophe Rosty
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia. .,Envoi Specialist Pathologists, Brisbane, QLD, 4059, Australia. .,Department of Pathology, University of Melbourne, Melbourne, VIC, 3010, Australia.
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Murakami T, Sakamoto N, Nagahara A. Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma. J Gastroenterol Hepatol 2019; 34:1685-1695. [PMID: 31158302 DOI: 10.1111/jgh.14752] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/22/2019] [Accepted: 05/28/2019] [Indexed: 12/17/2022]
Abstract
Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF-mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to "interval cancers" and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.
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Affiliation(s)
- Takashi Murakami
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Naoto Sakamoto
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
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Abstract
BACKGROUND Colonoscopy is effective for colorectal cancer (CRC) prevention, yet patients may develop CRC despite adhering to screening/surveillance intervals. There are limited data on predictive factors associated with these postcolonoscopy CRCs (PCCRCs). We aimed to measure PCCRC rates and identify risk factors for PCCRC. METHODS We performed a case-control study, comparing patients with PCCRCs to spontaneous CRCs diagnosed during a 12.5-year period at an academic medical center. PCCRCs were defined as CRCs diagnosed in between guideline-recommended screening/surveillance intervals. RESULTS During the 12.5-year period, of 1266 CRCs diagnosed, 122 (10%) were PCCRCs. 70% of PCCRCs were diagnosed within 5 years of a prior colonoscopy. There was an increasing trend for PCCRC rates in recent years [odds ratio (OR), 2.78; 95% confidence interval (CI), 1.51-5.09], with PCCRCs comprising 13.6% of cancers diagnosed in 2016 as compared with 5.7% of cancers diagnosed in 2005. Older age (OR per year, 1.02; 95% CI, 1.01-1.04), proximal colonic location (OR, 1.99; 95% CI, 1.20-3.33) and early stage (OR, 2.57; 95% CI, 1.34-4.95) were associated with PCCRCs. In total, 41% of PCCRCs were diagnosed by a different physician from the physician who did the prior colonoscopy, and 42% of physicians did not diagnose any of their PCCRC cases. CONCLUSIONS PCCRC rates are rising in recent years, likely reflecting the widespread adoption of colonoscopy as a primary screening tool, and are more common in older patients and those with proximal, early-stage tumors. The finding that a large proportion of PCCRCs are diagnosed by a different physician raises the concern that physicians are unaware of their own patients' PCCRCs.
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Abstract
CLINICAL PROBLEM Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality. Most colorectal cancers derive from benign precursor lesions, so-called adenomatous polyps, over a long period of time. Colorectal cancer screening is based on the detection of precancerous polyps and early stage CRC in asymptomatic individuals to reduce CRC incidence and mortality. The protective effect of screening programs can be improved by increasing the screening rates. PRACTICAL RECOMMENDATIONS Apart from the established examinations, CT colonography (CTC) has been proposed as an optional test for colorectal cancer screening. The detection rates of CTC for large polyps and cancer are similar to the ones of colonoscopy and superior to stool-based tests. CTC is therefore the radiological test of choice for the detection of colorectal neoplasia. It has replaced double contrast barium enema for almost all indications. As a minimally invasive procedure, CTC has a high safety profile and good patient acceptance. The evaluation of extracolonic organs in addition to the colon can increase examination efficacy. The option to choose CTC as a CRC screening test has the potential to increase the overall screening rates.
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