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Toyoshima O, Nishizawa T, Yoshida S, Arano T, Watanabe H, Mizutani H, Yamada T, Takatori Y, Ebinuma H, Saito Y. Characteristics of Clinically Significant Hyperplastic Polyps: Distinctions Between Microvesicular and Goblet Cell-Rich Types. J Gastroenterol Hepatol 2025; 40:1182-1187. [PMID: 40025862 DOI: 10.1111/jgh.16921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/07/2025] [Accepted: 02/14/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Clinically significant serrated polyps (CSSPs) are defined as sessile serrated lesions (SSLs), SSLs with dysplasia, traditional serrated adenomas (TSAs), hyperplastic polyps (HPs) ≥ 10 mm, and HPs ≥ 6 mm in the proximal colon. HPs are further classified as microvesicular HPs (MVHPs) and goblet cell-rich HPs (GCHPs). Among CSSPs, HPs were categorized into clinically significant MVHPs (CS-MVHPs) and clinically significant GCHPs (CS-GCHPs). This study compares the characteristics of CS-MVHPs, CS-GCHPs, and SSLs. METHODS This study included patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic between March 2021 and April 2024. Lesions diagnosed as adenomas or CSSPs were removed. Age, sex, number of polyps, detection rate, and polyp size were compared among CS-MVHPs, CS-GCHPs, and SSLs. RESULTS In total, 14 065 patients were enrolled. The detection rates for CS-MVHPs, CS-GCHPs, and SSLs were 5.24%, 1.22%, and 6.36%, respectively. Patients with CS-MVHPs or SSLs were significantly younger and more often female than those with CS-GCHPs. The mean sizes of CS-MVHPs and SSLs were significantly larger than that of CS-GCHPs. The detection rate of CS-GCHPs increased with age, whereas the detection rates of CS-MVHPs and SSLs did not show a similar trend. CONCLUSIONS Compared with CS-GCHPs, CS-MVHPs were larger, more frequent, and more likely to be found in younger patients and females. The characteristics of CS-MVHPs are similar to those of SSLs, supporting the hypothesis that CS-MVHPs are precursors of SSLs.
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Affiliation(s)
| | - Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | | | - Toru Arano
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | | | - Hiroya Mizutani
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoharu Yamada
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yusaku Takatori
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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Mottola M, Ricci C, Chiarucci F, Ravaioli C, Grillini A, Gherardi A, Fiorentino M, Bevilacqua A, Ambrosi F. Computer-Based Detection of Colorectal Serrated Lesions: Digital Flatness, a Novel Metric Designed for Whole-Slide Images. J Transl Med 2025; 105:104178. [PMID: 40258493 DOI: 10.1016/j.labinv.2025.104178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/04/2025] [Accepted: 04/12/2025] [Indexed: 04/23/2025] Open
Abstract
Colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) are characterized by sawtooth or stellate epithelial architecture. Distinguishing between SSLs and HPs is crucial as SSLs are precursors of colorectal carcinomas in 30% of cases, whereas HPs are likely precursors to SSLs. The differentiation of SSL from HP is primarily based on architectural features. Indeed, the hallmark of SSL is a substantial distortion of the typical crypt design and silhouette, which shows horizontal expansion along the muscularis mucosae and enlargement of the crypt base, especially in the lower third of the crypt. The ability to analyze digitized histologic images has led to innovative automated tissue analysis, thereby improving reproducibility and objectivity in pathologists' reports. Some recent studies explored colorectal cancer diagnosis and grading through automated quantitative analysis, but none of them focused on SSL detection. This study aimed to develop an automated method for SSL diagnosis by defining specific metrics to characterize their most common visual features. We developed a processing pipeline involving the automatic segmentation of all the tissue structures required for computing quantitative morphologic and architectural features, which allows detection of SSLs. In particular, we designed a novel metric, digital flatness, which numerically characterizes the parallelism of the gland's contour edges with the muscolaris mucosa profile. In a data set of 759 polyp glands, 41 of which were reported as SSLs by expert pathologists, our novel detection method achieved specificity of 92% and sensitivity of 83%, with accuracy of 92%. Our results represent a first approach to a simple, common, but still debated issue among gastrointestinal pathologists, thus providing valid support for the objective and standardized individuation of SSLs.
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Affiliation(s)
- Margherita Mottola
- Alma Mater Research Institute on Global Challenges and Climate Change, University of Bologna, Italy
| | - Costantino Ricci
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
| | - Federico Chiarucci
- Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
| | - Caterina Ravaioli
- Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
| | - Alessia Grillini
- Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
| | - Alessandro Gherardi
- Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
| | - Michelangelo Fiorentino
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy.
| | - Alessandro Bevilacqua
- Department of Computer Science and Engineering, University of Bologna, Italy; Advanced Research Center on Electronic Systems, University of Bologna, Italy
| | - Francesca Ambrosi
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Pathology Unit, Dipartimento InterAziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna, Italy
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Gallardo‐Gómez M, Costas‐Ríos L, Garcia‐Prieto CA, Álvarez‐Rodríguez L, Bujanda L, Barrero M, Castells A, Balaguer F, Jover R, Esteller M, Tardío Baiges A, González‐Carreró Fojón J, Cubiella J, De Chiara L. Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection. Mol Oncol 2024; 18:2696-2713. [PMID: 38129291 PMCID: PMC11547225 DOI: 10.1002/1878-0261.13573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/07/2023] [Accepted: 12/19/2023] [Indexed: 12/23/2023] Open
Abstract
The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions.
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Affiliation(s)
- María Gallardo‐Gómez
- CINBIO, Universidade de VigoSpain
- Department of Biochemistry, Genetics and ImmunologyUniversidade de VigoSpain
- Galicia Sur Health Research Institute (IIS Galicia Sur)SERGAS‐UVIGOSpain
| | - Lara Costas‐Ríos
- CINBIO, Universidade de VigoSpain
- Department of Biochemistry, Genetics and ImmunologyUniversidade de VigoSpain
| | - Carlos A. Garcia‐Prieto
- Josep Carreras Leukaemia Research Institute (IJC)BadalonaSpain
- Life Sciences DepartmentBarcelona Supercomputing Center (BSC)Spain
| | - Lara Álvarez‐Rodríguez
- CINBIO, Universidade de VigoSpain
- Department of Biochemistry, Genetics and ImmunologyUniversidade de VigoSpain
| | - Luis Bujanda
- Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)Universidad del País Vasco (UPV/EHU)San SebastiánSpain
| | - Maialen Barrero
- Department of OncologyHospital Universitario DonostiaSan SebastiánSpain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clínic, IDIBAPS, CIBERehdUniversity of BarcelonaSpain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clínic, IDIBAPS, CIBERehdUniversity of BarcelonaSpain
| | - Rodrigo Jover
- Servicio de Medicina Digestiva, Hospital General Universitario Dr. Balmis ISABIALUniversidad Miguel HernándezAlicanteSpain
| | - Manel Esteller
- Josep Carreras Leukaemia Research Institute (IJC)BadalonaSpain
- Centro de Investigacion Biomedica en Red Cancer (CIBERONC)MadridSpain
- Institució Catalana de Recerca i Estudis Avançats (ICREA)BarcelonaSpain
- Physiological Sciences Department, School of Medicine and Health SciencesUniversity of Barcelona (UB)Spain
| | - Antoni Tardío Baiges
- Department of PathologyHospital Álvaro Cunqueiro, Instituto de Investigación Biomédica Galicia SurVigoSpain
| | | | - Joaquín Cubiella
- Department of GastroenterologyComplexo Hospitalario Universitario de Ourense, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)OurenseSpain
| | - Loretta De Chiara
- CINBIO, Universidade de VigoSpain
- Department of Biochemistry, Genetics and ImmunologyUniversidade de VigoSpain
- Galicia Sur Health Research Institute (IIS Galicia Sur)SERGAS‐UVIGOSpain
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Zhang QQ, Wu JD, Li XY, Fang FF, Li GP, Bai T, Song J. Clinical and endoscopic characteristics of colorectal sessile serrated lesions with or without dysplasia/carcinoma: A systematic review and meta-analysis. J Dig Dis 2024; 25:424-435. [PMID: 39104049 DOI: 10.1111/1751-2980.13302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 06/05/2024] [Accepted: 06/29/2024] [Indexed: 08/07/2024]
Abstract
OBJECTIVE We aimed to compare the clinical and endoscopic characteristics of sessile serrated lesions (SSLs) with dysplasia/carcinoma (SSLD/Cs) and SSLs without dysplasia in this systematic review and meta-analysis. METHODS MEDLINE, EMBASE, and Cochrane Library databases and Clinicaltrials.gov were searched for relevant studies published up to August 28, 2023. The primary outcome was lesion size in SSLD/Cs and SSLs without dysplasia. The secondary outcomes included risk of dysplasia/carcinoma, morphology (classified based on the Paris classification), and lesion features such as mucus cap and nodules/protrusions in the two groups. RESULTS Thirteen studies with 14 381 patients were included. The proportion of SSLD/Cs ≥10 mm was significantly higher than that of SSLs without dysplasia (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.21-12.02, p = 0.02). There was no significant difference in the risk of dysplasia/carcinoma between the proximal (OR 0.80, 95% CI 0.57-1.14) and distal colon (OR 1.25, 95% CI 0.88-1.77, p = 0.21). The 0-Ip (OR 2.47, 95% CI 1.50-4.09) and 0-IIa + Is (OR 10.38, 95% CI 3.08-34.98) morphologies were more prevalent among SSLD/Cs, whereas the 0-IIa morphology (OR 0.38, 95% CI 0.22-0.65) was more prevalent among SSLs without dysplasia (all p < 0.001). Furthermore, mucus cap (OR 0.61, 95% CI 0.42-0.89, p = 0.01) was more common among SSLs without dysplasia, whereas nodules/protrusions (OR 7.80, 95% CI 3.07-19.85, p < 0.001) were more common in SSLD/Cs. CONCLUSION SSLs >10 mm, 0-Ip or 0-IIa + Is morphologies, and those with nodules/protrusions are significantly associated with dysplasia/carcinoma.
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Affiliation(s)
- Qing Qing Zhang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Jian Di Wu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Xue Yan Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Fei Fei Fang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Gang Ping Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Tao Bai
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Jun Song
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
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Choi Y, Kim N. Sex Difference of Colon Adenoma Pathway and Colorectal Carcinogenesis. World J Mens Health 2024; 42:256-282. [PMID: 37652658 PMCID: PMC10949019 DOI: 10.5534/wjmh.230085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 05/09/2023] [Indexed: 09/02/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common causes of cancer morbidity in both sexes but shows sex differences. First, sex-specific differences in tumor recurrence and survival rates have been reported. For example, the development of CRC is found about 1.5 times higher and 4-8 years earlier in males compared to females, suggesting the protective role of estrogen in the disease. Furthermore, female patients have a higher risk of developing right-sided (proximal) colon cancer than male patients, which is known to have more aggressive clinical character compared to left-sided (distal) colon cancer. That is, left and right CRCs show differences in carcinogenic mechanism, that the chromosomal instability pathway is more common in left colon cancer while the microsatellite instability and serrated pathways are more common in right colon cancer. It is thought that there are sex-based differences on the background of carcinogenesis of CRC. Sex differences of CRC have two aspects, sexual dimorphism (biological differences in hormones and genes) and gender differences (non-biological differences in societal attitudes and behavior). Recently, sex difference of colon adenoma pathway and sexual dimorphism in the biology of gene and protein expression, and in endocrine cellular signaling in the CRC carcinogenesis have been accumulated. In addition, behavioral patterns can lead to differences in exposure to risk factors such as drinking or smoking, diet and physical activity. Therefore, understanding sex/gender-related biological and sociocultural differences in CRC risk will help in providing strategies for screening, treatment and prevention protocols to reduce the mortality and improve the quality of life. In this review, sex/gender differences in colon adenoma pathway and various aspects such as clinicopathological, biological, molecular, and socio-cultural aspects of CRC were described.
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Affiliation(s)
- Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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Buja A, De Luca G, Zorzi M, Bovo E, Mocellin S, Trevisiol C, Bronte V, Guzzinati S, Rugge M. Thirty-two-year trends of cancer incidence by sex and cancer site in the Veneto Region from 1987 to 2019. Front Public Health 2024; 11:1267534. [PMID: 38259775 PMCID: PMC10800396 DOI: 10.3389/fpubh.2023.1267534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 12/13/2023] [Indexed: 01/24/2024] Open
Abstract
Background This observational study considers the sex-specific incidence of the most incident cancers as recorded in the population-based Veneto Regional Cancer Registry over a period of more than 30 years (1987-2019). Methods The Veneto Regional Cancer Registry collected data for the time interval 1987-2019. Significant changes in incidence trends calculated on age-standardized incidence rates (Annual Percent Change-APC) were identified by join point regression analysis. Results Overall, the incidence trend for all cancers decreased in males and remained stable in females. In nine cancer sites, the incidence trends showed consistent differences by sex (oral cavity, esophagus, colon rectum and anus, liver, larynx, lung, cutaneous malignant melanoma, bladder, and thyroid gland). Other malignancies did not show significant sex-related differences (stomach, pancreas, biliary tract, kidney/urinary tract, central nervous system, multiple myeloma, non-Hodgkin lymphoma, and leukemia). Conclusion In the period 1987-2019, this study revealed sex-related differences in cancer incidence trends. Over time, cancer incidence remained higher in males, with a decreasing epidemiological impact, plausibly resulting from prevention campaigns against environmental cancer risk factors, as tobacco and alcohol. Conversely, a significant decrease was not observed in the incidence trend in females. These findings contribute essential insights for profiling the epidemiological map of cancer in a large Italian population, allowing comparison with other European cancer epidemiology studies and providing updated data supporting sex-related primary and secondary cancer prevention strategies.
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Affiliation(s)
- Alessandra Buja
- Department of Cardiological, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Giuseppe De Luca
- Department of Cardiological, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Manuel Zorzi
- Veneto Tumour Registry, Azienda Zero, Padua, Italy
| | | | - Simone Mocellin
- Soft-Tissue, Peritoneum, and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy
- Department of Surgery, Oncology, and Gastroenterology – DISCOG, University of Padova, Padua, Italy
| | - Chiara Trevisiol
- Soft-Tissue, Peritoneum, and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy
| | | | | | - Massimo Rugge
- Veneto Tumour Registry, Azienda Zero, Padua, Italy
- Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy
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Wang RG, Ren YT, Jiang X, Wei L, Zhang XF, Liu H, Jiang B. Usefulness of analyzing endoscopic features in identifying the colorectal serrated sessile lesions with and without dysplasia. World J Clin Cases 2023; 11:6995-7003. [PMID: 37946753 PMCID: PMC10631427 DOI: 10.12998/wjcc.v11.i29.6995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 09/11/2023] [Accepted: 09/23/2023] [Indexed: 10/13/2023] Open
Abstract
BACKGROUND Sessile serrated lesions (SSLs) are often missed on colonoscopy, and studies have shown this to be an essential cause of interstitial colorectal cancer. The SSLs with dysplasia (SSL-D+), in particular, have a faster rate of carcinogenesis than conventional tubular adenomas. Therefore, there is a clinical need for some endoscopic features with independent diagnostic value for SSL-D+s to assist endoscopists in making immediate diagnoses, thus improving the quality of endoscopic examination and treatment. AIM To compare the characteristics of SSLs, including those with and without dysplasia (SSL-D+ and SSL-D-), based on white light and image-enhanced endoscopy, to achieve an immediate differential diagnosis for endoscopists. METHODS From January 2017 to February 2023, cases of colorectal SSLs confirmed by colonoscopy and histopathology at the Gastrointestinal Endoscopy Center of Beijing Tsinghua Changgung Hospital were collected. The general, endoscopic, and histopathological data were reviewed and analyzed to determine the diagnostic utility. Univariate analysis was used to find potential diagnostic factors, and then multivariate regression analysis was performed to derive endoscopic features with independent diagnostic values for the SSL-D+. RESULTS A total of 228 patients with 253 lesions were collected as a result. There were 225 cases of colorectal SSL-D-s and 28 cases of SSL-D+s. Compared to the colorectal SSL-D-, the SSL-D+ was more common in the right colon (P = 0.027) with complex patterns of depression, nodule, and elevation based on cloud-like surfaces (P = 0.003), reddish (P < 0.001), microvascular varicose (P < 0.001), and mixed type (Pit II, II-O, IIIL, IV) of crypt opening based on Pit II-O (P < 0.001). Multifactorial logistic regression analysis indicated that lesions had a reddish color [odds ratio (OR) = 18.705, 95% confidence interval (CI): 3.684-94.974], microvascular varicose (OR = 6.768, 95%CI: 1.717-26.677), and mixed pattern of crypt opening (OR = 20.704, 95%CI: 2.955-145.086) as the independent predictors for SSL-D+s. CONCLUSION The endoscopic feature that has independent diagnostic value for SSL-D+ is a reddish color, microvascular varicose, and mixed pattern of crypt openings.
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Affiliation(s)
- Rui-Gang Wang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yu-Tang Ren
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Xuan Jiang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Lai Wei
- Center for Hepatobiliary and Pancreatic Diseases, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Xiao-Fei Zhang
- Center for Clinical Epidemiology and Statistics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Hao Liu
- Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Bo Jiang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
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Utsumi T, Yamada Y, Diaz-Meco MT, Moscat J, Nakanishi Y. Sessile serrated lesions with dysplasia: is it possible to nip them in the bud? J Gastroenterol 2023; 58:705-717. [PMID: 37219625 PMCID: PMC10366009 DOI: 10.1007/s00535-023-02003-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 05/14/2023] [Indexed: 05/24/2023]
Abstract
The serrated neoplasia pathway constitutes an "alternative route" to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic (> 10-15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their flat shapes and the relatively short window of this intermediate state make it difficult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identified distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME). Molecular studies at the single-cell level have identified distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignant-SSLs. Recent progress in all aspects of the field has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications.
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Affiliation(s)
- Takahiro Utsumi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Yosuke Yamada
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - Maria Teresa Diaz-Meco
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA
| | - Jorge Moscat
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY, USA
| | - Yuki Nakanishi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
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Qiao D, Liu XY, Zheng L, Zhang YL, Que RY, Ge BJ, Cao HY, Dai YC. Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types. World J Clin Cases 2023; 11:1963-1973. [PMID: 36998954 PMCID: PMC10044969 DOI: 10.12998/wjcc.v11.i9.1963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 02/12/2023] [Accepted: 03/03/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, with the fourth highest mortality among all cancers. Reportedly, in addition to adenomas, serrated polyps, which account for 15%-30% of CRCs, can also develop into CRCs through the serrated pathway. Sessile serrated adenomas/polyps (SSAs/Ps), a type of serrated polyps, are easily misdiagnosed during endoscopy. AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types. METHODS From January 2021 to December 2021, patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. Thirty cases each of large intestine damp-heat (Da-Chang-Shi-Re, DCSR) syndrome and spleen-stomach weakness (Pi-Wei-Xu-Ruo) syndrome were reported. Baseline comparison of the general data, typical tongue coating, colonoscopy findings, and hematoxylin and eosin findings was performed in each group. The expression of the Wnt pathway-related proteins, namely β-catenin, adenomatous polyposis coli, and mutated in colorectal cancer, were analyzed using immunohistochemistry. RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types (P = 0.001). The other aspects did not differ between the two groups. The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups, which was manifested as β-catenin protein translocation into the nucleus. However, SSAs/Ps patients with DCSR syndrome had more nucleation, higher β-catenin expression, and negative regulatory factor (adenomatous polyposis coli and mutated in colorectal cancer) expression (P < 0.0001) than SSA/P patients with Pi-Wei-Xu-Ruo syndrome. In addition, the SSA/P size was linearly correlated with the related protein expression. CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis. A high-quality colonoscopic diagnosis was essential. The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.
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Affiliation(s)
- Dan Qiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Xiao-Yan Liu
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Lie Zheng
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Xi’an, Xi’an 730000, Shaanxi Province, China
| | - Ya-Li Zhang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Ren-Ye Que
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Bing-Jing Ge
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Hong-Yan Cao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
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Cai H, Feng X, Yin R, Zhao Y, Guo L, Fan X, Liao J. MIST: multiple instance learning network based on Swin Transformer for whole slide image classification of colorectal adenomas. J Pathol 2023; 259:125-135. [PMID: 36318158 DOI: 10.1002/path.6027] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 09/30/2022] [Accepted: 10/28/2022] [Indexed: 12/12/2022]
Abstract
Colorectal adenoma is a recognized precancerous lesion of colorectal cancer (CRC), and at least 80% of colorectal cancers are malignantly transformed from it. Therefore, it is essential to distinguish benign from malignant adenomas in the early screening of colorectal cancer. Many deep learning computational pathology studies based on whole slide images (WSIs) have been proposed. Most approaches require manual annotation of lesion regions on WSIs, which is time-consuming and labor-intensive. This study proposes a new approach, MIST - Multiple Instance learning network based on the Swin Transformer, which can accurately classify colorectal adenoma WSIs only with slide-level labels. MIST uses the Swin Transformer as the backbone to extract features of images through self-supervised contrastive learning and uses a dual-stream multiple instance learning network to predict the class of slides. We trained and validated MIST on 666 WSIs collected from 480 colorectal adenoma patients in the Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School. These slides contained six common types of colorectal adenomas. The accuracy of external validation on 273 newly collected WSIs from Nanjing First Hospital was 0.784, which was superior to the existing methods and reached a level comparable to that of the local pathologist's accuracy of 0.806. Finally, we analyzed the interpretability of MIST and observed that the lesion areas of interest in MIST were generally consistent with those of interest to local pathologists. In conclusion, MIST is a low-burden, interpretable, and effective approach that can be used in colorectal cancer screening and may lead to a potential reduction in the mortality of CRC patients by assisting clinicians in the decision-making process. © 2022 The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Hongbin Cai
- School of Science, China Pharmaceutical University, Nanjing, PR China
| | - Xiaobing Feng
- College of Electrical and Information Engineering, Hunan University, Changsha, PR China
| | - Ruomeng Yin
- School of Science, China Pharmaceutical University, Nanjing, PR China
| | - Youcai Zhao
- Department of Pathology, Nanjing First Hospital, Nanjing, PR China
| | - Lingchuan Guo
- Department of Pathology, The First Affiliated Hospital of Soochow University, Soochow, PR China
| | - Xiangshan Fan
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China
| | - Jun Liao
- School of Science, China Pharmaceutical University, Nanjing, PR China
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11
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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: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 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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Bayrak T, Çetin Z, Saygılı Eİ, Ogul H. Identifying the tumor location-associated candidate genes in development of new drugs for colorectal cancer using machine-learning-based approach. Med Biol Eng Comput 2022; 60:2877-2897. [DOI: 10.1007/s11517-022-02641-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 07/28/2022] [Indexed: 02/07/2023]
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Antonelli G, Correale L, Spadaccini M, Maselli R, Bhandari P, Bisschops R, Cereatti F, Dekker E, East JE, Iacopini F, Jover R, Kiesslich R, Pellise M, Sharma P, Rex DK, Repici A, Hassan C. Dye-based chromoendoscopy for the detection of colorectal neoplasia: meta-analysis of randomized controlled trials. Gastrointest Endosc 2022; 96:411-422. [PMID: 35588768 DOI: 10.1016/j.gie.2022.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/10/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Dye-based chromoendoscopy (DBC) could be effective in increasing the adenoma detection rate (ADR) in patients undergoing colonoscopy, but the technique is time-consuming and its uptake is limited. We aimed to assess the effect of DBC on ADR based on available randomized controlled trials (RCTs). METHODS Four databases were searched up to April 2022 for RCTs comparing DBC with conventional colonoscopy (CC) in terms of ADR, advanced ADR, and sessile serrated adenoma detection rate as well as the mean adenomas per patient and non-neoplastic lesions. Relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes were calculated using random-effect models. The I2 test was used for quantifying heterogeneity. Risk of bias was evaluated with the Cochrane tool. RESULTS Overall, 10 RCTs (5334 patients) were included. Indication for colonoscopy was screening or surveillance (3 studies) and mixed (7 studies). Pooled ADR was higher in the DBC group versus the CC group (95% CI, 48.1% [41.4%-54.8%] vs 39.3% [33.5%-46.4%]; RR, 1.20 [1.11-1.29]), with low heterogeneity (I2 = 29%). This effect was consistent for advanced ADR (RR, 1.21 [1.03-1.42]; I2 = .0%), sessile serrated adenomas (6.1% vs 3.5%; RR, 1.68 [1.15-2.47]; I2 = 9.8%), and mean adenomas per patient (MD, .24 [.17-.31]) overall and in the right-sided colon (MD, .28 [.14-.43]). A subgroup analysis considering only trials using high-definition white-light endoscopy reduced the heterogeneity while still showing a significant increase in adenoma detection with DBC: 51.6% (95% confidence interval [CI], 47.1%-56.1%) and 59.1% (95% CI, 54.7-63.3%), RR = 1.14 (95% CI, 1.06-1.23), P = .0004, I2 = .0%, P = .50. CONCLUSIONS Meta-analysis of RCTs showed that DBC increases key quality parameters in colonoscopy, supporting its use in everyday clinical practice.
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Affiliation(s)
- Giulio Antonelli
- Gastroenterology and Digestive Endoscopy Unit, Ospedale dei Castelli Hospital, Ariccia, Rome, Italy; Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy
| | - Loredana Correale
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Marco Spadaccini
- Endoscopy Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Roberta Maselli
- Endoscopy Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Pradeep Bhandari
- Department of Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
| | - Raf Bisschops
- Department of Gastroenterology and Hepatology, Catholic University of Leuven, (KUL), TARGID, University Hospital Leuven, Leuven, Belgium
| | - Fabrizio Cereatti
- Gastroenterology and Digestive Endoscopy Unit, Ospedale dei Castelli Hospital, Ariccia, Rome, Italy
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - James E East
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, John Radcliffe Hospital, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK; Division of Gastroenterology and Hepatology, Mayo Clinic Healthcare, London, UK
| | - Federico Iacopini
- Gastroenterology and Digestive Endoscopy Unit, Ospedale dei Castelli Hospital, Ariccia, Rome, Italy
| | - Rodrigo Jover
- Servicio de Gastroenterología, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB) & Centro de Investigación Biomédica de Canarias (CIBICAN), Santa Cruz de Tenerife, Spain
| | - Ralph Kiesslich
- Department of Internal Medicine II Gastroenterology, Hepatology and Endocrinology, Helios Dr Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
| | - Maria Pellise
- Gastroenterology Department, Endoscopy Unit, ICMDiM, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Catalonia, Spain
| | - Prateek Sharma
- Department of Gastroenterology and Hepatology, Kansas City VA Medical Center, Kansas City, Missouri, USA
| | - Douglas K Rex
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Endoscopy Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Endoscopy Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
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14
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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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15
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Batts KP, Cinnor B, Kim A, Stickney E, Burgart LJ. Sessile Serrated Adenoma With Dysplasia of the Colon. Am J Clin Pathol 2022; 157:180-195. [PMID: 34542560 DOI: 10.1093/ajcp/aqab112] [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] [Received: 03/11/2021] [Accepted: 06/01/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Sessile serrated adenomas with dysplasia (SSADs) of the colon are transitional lesions between sessile serrated adenomas (SSAs) and a subset of colorectal adenocarcinomas. We wished to gain insight into the relative percentages and significance of SSAD subtypes. METHODS Retrospective (2007-2012) clinicopathologic review of colorectal polyps initially regarded as having mixed serrated and dysplastic elements. SSADs were subdivided into those with cap-like adenomatous dysplasia (ad1), non-cap-like adenomatous dysplasia (ad2), serrated dysplasia (ser), minimal dysplasia (min), and dysplasia not otherwise specified (nos). MLH1 immunostaining was performed on many. RESULTS SSADser (7.7%) had a greater propensity for right colon, women, and MLH1 loss vs the entire cohort. SSAad1 (11.6%) had the least female preponderance, was least likely to have MLH1 loss, and was most likely to affect the left colorectum. SSAD with MLH1 loss was associated with an increased burden of SSAs in the background colon (P = .0003) but not tubular adenomas or hyperplastic polyps. Most SSADs (ad2 and nos groups, 80% combined) showed difficult-to-classify dysplasia, intermediate MLH1 loss rates, and intermediate clinical features. CONCLUSIONS While some trends exist, morphologically subclassifying SSADs is probably not justified in routine clinical practice. MLH1 loss portends a greater burden of SSAs in the background colon.
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Affiliation(s)
| | | | - Adam Kim
- MNGI Digestive Health, Minneapolis, MN, USA
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Manning J, Halonen J, Cheriyamkunnel SJ, Álvarez-González MA. 1L NER1006 can improve rates of adequate and high-quality bowel cleansing in the right colon: a post hoc analysis of two randomised clinical trials. BMC Gastroenterol 2022; 22:35. [PMID: 35078404 PMCID: PMC8787873 DOI: 10.1186/s12876-022-02106-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 01/05/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The right colon is difficult to cleanse compared with other colon segments. This post hoc analysis of two randomised clinical trials (MORA and NOCT) examined whether 1L polyethylene glycol (PEG) NER1006 and two mid-volume alternatives could improve adequate and high-quality cleansing in the right colon among patients with complete cleansing assessments. METHODS Patients received NER1006 (N2D), 2L PEG plus ascorbate (2LPEG) or oral sulphate solution (OSS) as a 2-day evening/morning split-dosing regimen or NER1006 as a same-day morning-only dosing regimen (N1D). Patients had full segmental scoring assigned by treatment-blinded central readers using the Harefield Cleansing Scale. The right colon adequate (score ≥ 2) and high-quality (score ≥ 3) cleansing success of NER1006 (N2D and N1D) versus 2LPEG and OSS was analysed individually and as pooled groups (N2D vs. 2LPEG/OSS). We assessed the comparative right colon cleansing rates of the N2D versus 2LPEG/OSS in overweight males. We also performed a multivariable regression analysis to examine factors affecting cleansing in the right colon. RESULTS A total of 1307 patients were included. Pooled N2D showed significantly improved rates of adequate-level cleansing in the right colon compared with 2LPEG (97.5% [504/517] vs. 94.6% [246/260]; p = 0.020) and OSS (97.5% [504/517] vs. 93.8% [244/260]; p = 0.006). In MORA, the rate of adequate right colon cleansing did not significantly differ between N1D and 2LPEG (95.2% [257/270] vs. 94.6% [246/260]; p = 0.383). The rate of right colon high-quality cleansing was significantly improved with N2D or N1D vs. 2LPEG (p < 0.001 for both), and was numerically higher with N2D versus OSS (p = 0.11). In overweight males, NER1006 delivered numerically higher adequate (p = 0.398) and superior high-quality (p = 0.024) cleansing rates versus 2LPEG/OSS. Multivariable regression analysis showed NER1006 was associated with adequate and high-quality cleansing (p = 0.031 and p < 0.001), while time between preparation and colonoscopy was negatively associated (p = 0.034 and p = 0.006). CONCLUSIONS NER1006 delivered improved rates of adequate and high-quality right colon cleansing compared with 2LPEG and OSS. The increased rate of high-quality cleansing with NER1006 versus its comparators was also seen in overweight males.
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Affiliation(s)
- Jonathan Manning
- Borders General Hospital, NHS Borders, Melrose, Berwickshire, UK
| | - Juha Halonen
- Norgine Ltd, Medical Affairs, Widewater Place Moorhall Road, Harefield, Uxbridge, UB9 6NS, UK.
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Lu D, Wang M, Ke X, Wang Q, Wang J, Li D, Wang M, Wang Q. Association Between H. pylori Infection and Colorectal Polyps: A Meta-Analysis of Observational Studies. Front Med (Lausanne) 2022; 8:706036. [PMID: 35118081 PMCID: PMC8803908 DOI: 10.3389/fmed.2021.706036] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 12/20/2021] [Indexed: 11/18/2022] Open
Abstract
Background It has been suggested that Helicobacter pylori (H. pylori) infection is associated with hypergastrinemia and proliferation of colorectal mucosa via direct stimulation, dysbiosis of the gut microbiome, and changes in the gut microbiome, all of which may lead to the formation of colorectal polyps. However, the consensus remains lacking regarding whether H. pylori infection is independently associated with colorectal polyps and whether the association differs according to histological type of colorectal polyps. To summarize the current evidence regarding the relationship between H. pylori infection and colorectal polyps, we conducted a meta-analysis of related observational studies according to the histological types of colorectal polyps. Methods Observational studies investigating the association between H. pylori infection and colorectal polyps using multivariate analyses were included by search of PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results. Results Seventeen studies that include 322,395 participants were analyzed. It was shown that H. pylori infection was independently associated with overall colorectal polyps (odds ratio [OR]: 1.67, 95% CI: 1.24–2.24, p < 0.001; I2 = 73%). According to the histological type of colorectal polyps, H. pylori infection was independently associated with adenomatous polyps (APs; OR: 1.71, 95% CI: 1.47–1.99, p < 0.001; I2 = 86%), advanced APs (OR: 2.06, 95% CI: 1.56–2.73, p < 0.001; I2 = 0%), and hyperplastic polyps (HPs; OR: 1.54, 95% CI: 1.02–2.30, p = 0.04; I2 = 78%). Evidence based on only one study showed that H. pylori infection was not associated with sessile serrated polyps (SSPs; OR: 1.00, 95% CI: 0.93–1.07, p = 0.99). Conclusions Current evidence from case-control and cross-sectional studies suggested that H. pylori infection was independently associated with colorectal APs, advanced APs, and HPs, but not with SSPs. These findings suggested H. pylori infection may be a possible risk factor of colorectal polyp, which is important for the prevention of colorectal polyp in the adult population.
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Affiliation(s)
- Depeng Lu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Mingyu Wang
- Department of Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qiangwu Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jianchao Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Dapeng Li
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Meng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- *Correspondence: Qizhi Wang
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Shiu SI, Kashida H, Komeda Y. The prevalence of sessile serrated lesion in the colorectum and its relationship to synchronous colorectal advanced neoplasia: a systemic review and meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:1495-1504. [PMID: 33470706 PMCID: PMC8555953 DOI: 10.1097/meg.0000000000002062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/18/2020] [Indexed: 12/10/2022]
Abstract
BACKGROUND The aim of this systemic review and meta-analysis was to evaluate the prevalence of sessile serrated lesion (SSL) and its relationship to synchronous colorectal advanced neoplasia. MATERIALS AND METHODS Comprehensive, computerized research was performed on PubMed and published from 1 January 2010 to 6 July 2018 which searched relevant articles without any language limitations. Clinical trials were included in the narrative systemic review if they matched the following inclusion criteria: (1) published as a case-controlled study, cohort study or cross-sectional study; (2) defined objectively for diagnosis of SSL within the studies; (3) addressed the prevalence and characteristics of SSL. Within these trials, if they met additional criteria involving the reported outcome of risk regarding advanced neoplasia in relation to SSL, they were enrolled into meta-analysis. RESULTS Forty-one trials were enrolled for the systematic review, with a total of eight analyzed for the meta-analysis. The prevalence of all SSL ranged from 0.038 to 20.23% and the prevalence by pooled analysis was 2.7%. In a subgroup analysis, the overall prevalence of SSL during the periods of 2010-2014 and 2015-2018 was shown to be 2.7 and 2.8%, respectively. We calculated the pooled data on the cancer risk of SSL and the risk of synchronous advanced neoplasia in patients with SSL made available from the eight trials, which resulted in a pooled odds ratio of 3.53 (95% confidence interval 2.39-5.20, I2 = 4%, P = 0.40). CONCLUSION In this systemic review, SSL was found to be associated with an increased risk of synchronous advanced neoplasia in the colorectum.
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Affiliation(s)
- Sz-Iuan Shiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital
- Department of Critical Care Medicine, Taichung Veterans General Hospital
- Evidence-based Practice and Policymaking Committee, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Hiroshi Kashida
- Department of Gastroenterology and Hepatology, Kindai University, Osakasayama, Japan
| | - Yoriaki Komeda
- Department of Gastroenterology and Hepatology, Kindai University, Osakasayama, Japan
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19
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Shao PP, Shao CR, Romero T, Leung FW. Sessile serrated adenoma/polyp detection rate of water exchange, Endocuff, and cap colonoscopy: A network meta-analysis. J Gastroenterol Hepatol 2021; 36:3268-3277. [PMID: 34622488 DOI: 10.1111/jgh.15702] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 09/15/2021] [Accepted: 09/28/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Sessile serrated adenoma/polyp (SSA/P) may contribute to interval cancer. In a recent meta-analysis, water exchange (WE) was shown to be superior to Endocuff and cap colonoscopy at adenoma and advanced adenoma detection. The strong positive correlation between adenoma detection rate (ADR), advanced adenoma detection rate (AADR), and sessile serrated adenoma/polyp detection rate (SSA/PDR) prompted us to hypothesize that WE could significantly improve SSA/PDR compared with Endocuff and cap colonoscopy. METHODS The literature was searched for all randomized controlled trials (RCTs) that reported SSA/PDR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing SSA/PDR of each method using air insufflation as the control and reported the odds ratios (ORs) with 95% confidence interval (CI). Performances were ranked based on P-score. RESULTS A total of 531 articles resulted from initial keywords search. Eleven RCTs were included in the analysis. A total of 7856 patients underwent air insufflation, WE, Endocuff, or cap colonoscopy. WE significantly increased SSA/PDR (OR 2.04; 95% CI 1.33-3.13). Endocuff (OR 1.15; 95% CI 0.94-1.41) and cap (OR 1.08; 95% CI 0.42-2.74) did not significantly impact SSA/P detection. P-scores for WE (0.96), Endocuff (0.49), cap (0.37), and air insufflation (0.17) suggested that WE had the highest SSA/PDR. The results did not change after adjusting for mean withdrawal time and indication for colonoscopy. CONCLUSION Water exchange significantly increases SSA/PDR and is superior to Endocuff and cap colonoscopy at detecting SSA/P.
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Affiliation(s)
- Paul P Shao
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
- VA Sepulveda Ambulatory Care Center, North Hills, California, USA
- David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | | | - Tahmineh Romero
- David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Felix W Leung
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
- VA Sepulveda Ambulatory Care Center, North Hills, California, USA
- David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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20
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Chen T, Xu A, Lian J, Chu Y, Zhang H, Xu M. Transcolonic endoscopic appendectomy: a novel natural orifice transluminal endoscopic surgery (NOTES) technique for the sessile serrated lesions involving the appendiceal orifice. Gut 2021; 70:1812-1814. [PMID: 33483328 PMCID: PMC8458066 DOI: 10.1136/gutjnl-2020-323018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/03/2021] [Accepted: 01/08/2021] [Indexed: 01/25/2023]
Affiliation(s)
- Tao Chen
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Aiping Xu
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jingjing Lian
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuan Chu
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Haibin Zhang
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Meidong Xu
- Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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21
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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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22
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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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23
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Nishimura H, Fukui H, Wang X, Ebisutani N, Nakanishi T, Tomita T, Oshima T, Hirota S, Miwa H. Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum. Pathogens 2021; 10:pathogens10040434. [PMID: 33917384 PMCID: PMC8067346 DOI: 10.3390/pathogens10040434] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/30/2021] [Accepted: 04/02/2021] [Indexed: 12/24/2022] Open
Abstract
Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.
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Affiliation(s)
- Heihachiro Nishimura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Hirokazu Fukui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
- Correspondence: ; Tel.: +81-798-456-662
| | - Xuan Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Nobuhiko Ebisutani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Takashi Nakanishi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Toshihiko Tomita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Tadayuki Oshima
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
| | - Seiichi Hirota
- Department of Surgical Pathology, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan;
| | - Hiroto Miwa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan; (H.N.); (X.W.); (N.E.); (T.N.); (T.T.); (T.O.); (H.M.)
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Affiliation(s)
- Rashid N Lui
- Department of Medicine and Therapeutics
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Joseph Jy Sung
- Department of Medicine and Therapeutics
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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25
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Fujiwara-Tani R, Fujii K, Mori S, Kishi S, Sasaki T, Ohmori H, Nakashima C, Kawahara I, Nishiguchi Y, Mori T, Sho M, Kondoh M, Luo Y, Kuniyasu H. Role of Clostridium perfringens Enterotoxin on YAP Activation in Colonic Sessile Serrated Adenoma/ Polyps with Dysplasia. Int J Mol Sci 2020; 21:ijms21113840. [PMID: 32481659 PMCID: PMC7313056 DOI: 10.3390/ijms21113840] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/26/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022] Open
Abstract
Sessile serrated adenoma/polyp with dysplasia (SSA/P-D) is an SSA/P with cellular dysplasia and has a higher risk of progressing to colon carcinogenesis. Previously, we reported that tight junction impairment by Clostridiumperfringens enterotoxin (CPE) leads to activation of the transcriptional co-activator yes-associated protein (YAP) in oral squamous cell carcinoma. Here, we investigated whether CPE activates YAP to promote the malignant progression of SSA/P. E-cadherin expression was lower in the 12 cases with SSA/P-D examined than that in normal mucosa, SSA/P, or tubular adenoma (TA). Furthermore, intracellular translocation of claudin-4 (CLDN4) and nuclear translocation of YAP were observed. The CPE gene was detected in DNA extracted from SSA/P-D lesions, but not in SSA/P or TA. Treatment of the rat intestinal epithelial cell line IEC6 with low-dose CPE resulted in intracellular translocation of CLDN4 to the cytoplasmic membrane. Cytoplasmic CLDN4 showed co-precipitation with transcriptional co-activator with PDZ-binding motif, zonula occludens (ZO)-1, large tumor suppressor, and mammalian Ste20-like. Additionally, YAP co-precipitated with ZO-2 under CPE treatment led to decreased YAP phosphorylation and nuclear translocation. YAP activation promoted increase in nuclear TEA domain family member level, expression of cyclin D1, snail, vimentin, CD44, NS and decrease in E-cadherin levels, thereby inducing stemness and epithelial-mesenchymal-transition (EMT). The Hippo complex with the incorporation of CLDN4 increased stability. Upon low-dose CPE treatment, HT29 cells with BRAFV600E gene mutation showed increased growth, enhanced invasive potential, stemness, and induced EMT phenotype, whereas HCT116 cells, which carry KRASG13D gene mutation, did not show such changes. In an examination of 10 colorectal cancers, an increase in EMT and stemness was observed in CPE (+) and BRAF mutation (+) cases. These findings suggest that C.perfringens might enhance the malignant transformation of SSA/P-D via YAP activation. Our findings further highlight the importance of controlling intestinal flora using probiotics or antibiotics.
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Affiliation(s)
- Rina Fujiwara-Tani
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Kiyomu Fujii
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Shiori Mori
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Shingo Kishi
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Takamitsu Sasaki
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Hitoshi Ohmori
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Chie Nakashima
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Isao Kawahara
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Yukiko Nishiguchi
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Takuya Mori
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan;
| | - Masuo Kondoh
- Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University, 6-1 Yamadaoka, Suita, Osaka 565-0871, Japan;
| | - Yi Luo
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu Province, China
- Correspondence: (Y.L.); (H.K.); Tel.: +86-0513-8505-1805 (Y.L.); +81-744-22-3051 (H.K.); Fax: +81-744-25-7308 (H.K.)
| | - Hiroki Kuniyasu
- Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; (R.F.-T.); (K.F.); (S.M.); (S.K.); (T.S.); (H.O.); (C.N.); (I.K.); (Y.N.); (T.M.)
- Correspondence: (Y.L.); (H.K.); Tel.: +86-0513-8505-1805 (Y.L.); +81-744-22-3051 (H.K.); Fax: +81-744-25-7308 (H.K.)
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Lui RN, Sung JJY. Sessile serrated adenoma/polyps: Why we should be working flat out to understand more about these flat lesions? J Gastroenterol Hepatol 2019; 34:1667-1668. [PMID: 31726488 DOI: 10.1111/jgh.14891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Rashid N Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China
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