|
1
|
Ji S, Hu H, Zhu R, Guo D, Liu Y, Yang Y, Li T, Zou C, Jiang Y, Liu G. Integrative Multi-Omics Analysis Reveals Critical Molecular Networks Linking Intestinal-System Diseases to Colorectal Cancer Progression. Biomedicines 2024; 12:2656. [PMID: 39767563 PMCID: PMC11673540 DOI: 10.3390/biomedicines12122656] [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: 10/23/2024] [Revised: 11/14/2024] [Accepted: 11/16/2024] [Indexed: 01/06/2025] Open
Abstract
Background/Objectives: Colorectal cancer (CRC) frequently co-occurs with intestinal system diseases (ISDs), yet their molecular interplay remains poorly understood. We employed a comprehensive bioinformatics approach to elucidate shared genetic signatures and pathways between CRC and ISDs. Methods: We systematically analyzed 12 microarray and RNA-seq datasets encompassing 989 samples across seven ISDs and CRC. Differentially expressed genes (DEGs) were identified using Limma and DESeq2. Functional enrichment analysis was performed using clusterProfiler. Protein-protein interaction networks were constructed via STRING and visualized with Cytoscape to identify hub genes. Clinical significance of shared genes was further assessed through survival analysis and validated by immunohistochemistry staining of 30 paired CRC-normal tissue samples. Results: Integrating bioinformatics and machine learning approaches, we uncovered 160 shared DEGs (87 upregulated, 73 downregulated), which predominantly enriched cell metabolism, immune homeostasis, gut-brain communication, and inflammation pathways. Network analysis revealed nine key hub proteins linking CRC and ISDs, with seven upregulated (CD44, MYC, IL17A, CXCL1, FCGR3A, SPP1, and IL1A) and two downregulated (CXCL12 and CCL5). Survival analysis demonstrated the prognostic potential of these shared genes, while immunohistochemistry confirmed their differential expression in CRC tissues. Conclusions: Our findings unveil potential biomarkers and therapeutic targets, providing insights into ISD-influenced CRC progression and offering a robust foundation for improved diagnostic and treatment strategies in ISD-associated CRC.
Collapse
Affiliation(s)
- Shiliang Ji
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Haoran Hu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China;
| | - Ruifang Zhu
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Dongkai Guo
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Yujing Liu
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Yang Yang
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Tian Li
- School of Basic Medicine, Tianjin Medical University, Tianjin 300102, China;
| | - Chen Zou
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Yiguo Jiang
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
| | - Guilai Liu
- Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou 215163, China; (S.J.); (R.Z.); (D.G.); (Y.L.); (Y.Y.)
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| |
Collapse
|
|
2
|
Tran TH, Nguyen VH, Vo DTN. How to "pick up" colorectal serrated lesions and polyps in daily histopathology practice: From terminologies to diagnostic pitfalls. World J Clin Oncol 2024; 15:1157-1167. [PMID: 39351466 PMCID: PMC11438847 DOI: 10.5306/wjco.v15.i9.1157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 06/27/2024] [Accepted: 07/31/2024] [Indexed: 08/29/2024] Open
Abstract
Over the last decade, our knowledge of colorectal serrated polyps and lesions has significantly improved due to numerous studies on this group of precursor lesions. Serrated lesions were misleading as benign before 2010, but they are currently reclassified as precancerous lesions that contribute to 30% of colorectal cancer through the serrated neoplasia pathway. The World Health Organization updated the classification for serrated lesions and polyps of the colon and rectum in 2019, which is more concise and applicable in daily practice. The responsible authors prescribe that "colorectal serrated lesions and polyps are characterized by a serrated (sawtooth or stellate) architecture of the epithelium." From a clinical standpoint, sessile serrated lesion (SSL) and SSL with dysplasia (SSLD) are the two most significant entities. Despite these advancements, the precise diagnosis of SSL and SSLD based mainly on histopathology remains challenging due to various difficulties. This review describes the nomenclature and the terminology of colorectal serrated polyps and lesions and highlights the diagnostic criteria and obstacles encountered in the histopathological diagnosis of SSL and SSLD.
Collapse
Affiliation(s)
- Thai H Tran
- Department of Pathology, Da Nang Hospital, Da Nang 50000, Viet Nam
| | - Vinh H Nguyen
- Department of Pathology, University Medical Center Ho Chi Minh City, Ho Chi Minh 70000, Viet Nam
| | - Diem TN Vo
- Department of Pathology, University Medical Center Ho Chi Minh City, Ho Chi Minh 70000, Viet Nam
- Department of Histology-Embryology and Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh 70000, Viet Nam
| |
Collapse
|
|
3
|
Polychronidis G, He MM, Vithayathil M, Knudsen MD, Wang K, Song M. Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use. Gut 2024; 73:1675-1683. [PMID: 38839270 DOI: 10.1136/gutjnl-2023-331729] [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: 12/11/2023] [Accepted: 05/20/2024] [Indexed: 06/07/2024]
Abstract
BACKGROUND Surveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals for surveillance remain unclear. DESIGN We prospectively followed 156 699 participants who had undergone a colonoscopy from 2007 to 2017 in a large integrated healthcare system. Using multivariable Cox proportional hazards regression we estimated the subsequent risk of CRC and high-risk polyps, respectively, according to index colonoscopy polyps, colonoscopy quality measures, patient characteristics and the use of surveillance colonoscopy. RESULTS After a median follow-up of 5.3 years, we documented 309 CRC and 3053 high-risk polyp cases. Compared with participants with no polyps at index colonoscopy, those with high-risk adenomas and high-risk serrated polyps had a consistently higher risk of CRC during follow-up, with the highest risk observed at 3 years after polypectomy (multivariable HR 5.44 (95% CI 3.56 to 8.29) and 8.35 (95% CI 4.20 to 16.59), respectively). Recurrence of high-risk polyps showed a similar risk distribution. The use of surveillance colonoscopy was associated with lower risk of CRC, with an HR of 0.61 (95% CI 0.39 to 0.98) among patients with high-risk polyps and 0.57 (95% CI 0.35 to 0.92) among low-risk polyps. Among 1548 patients who had high-risk polyps at both index and surveillance colonoscopies, 65% had their index polyps in the proximal colon and 30% had index and interval polyps in the same segments. CONCLUSION Patients with high-risk polyp findings were at higher risk of subsequent CRC and high-risk polyps and may benefit from early surveillance within 3 years. The subsite distribution of the index and recurrent high-risk polyps suggests the contribution of incomplete resection and missed lesions to the development of interval neoplasia.
Collapse
Affiliation(s)
- Georgios Polychronidis
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of General,Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Study Centre of the German Surgical Society, German Surgical Society/Heidelberg University Hospital, Heidelberg, Germany
| | - Ming-Ming He
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- State Key Laboratory of Oncology in South China, Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mathew Vithayathil
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Imperial College Healthcare NHS Trust, London, UK
| | - Markus D Knudsen
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway
- Department of Transplantation Medicine, Division of Surgery,Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Kai Wang
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| |
Collapse
|
|
4
|
Wu Z, Yao L, Liu W, Zhang S, Zhang L, Lu Z, Wang J, Chen B, Luo R, Li X, Gong R, Luo C, Xu Y, Zeng Z, Yu H. Development and Validation of a Deep Learning-Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions. Am J Clin Pathol 2023; 160:394-403. [PMID: 37279532 DOI: 10.1093/ajcp/aqad058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 05/01/2023] [Indexed: 06/08/2023] Open
Abstract
OBJECTIVES The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)-based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. METHODS The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. RESULTS The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. CONCLUSIONS This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models.
Collapse
Affiliation(s)
- Zhifeng Wu
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Liwen Yao
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Wen Liu
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shiying Zhang
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Lihui Zhang
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Zihua Lu
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Jing Wang
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Boru Chen
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Renquan Luo
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Xun Li
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Rongrong Gong
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Chaijie Luo
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Youming Xu
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| | - Zhi Zeng
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Honggang Yu
- Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision
| |
Collapse
|
|
5
|
Chandramohan K, Balan DJ, Devi KP, Nabavi SF, Reshadat S, Khayatkashani M, Mahmoodifar S, Filosa R, Amirkhalili N, Pishvaei S, Aval OS, Nabavi SM. Short interfering RNA in colorectal cancer: is it wise to shoot the messenger? Eur J Pharmacol 2023; 949:175699. [PMID: 37011722 DOI: 10.1016/j.ejphar.2023.175699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 03/23/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023]
Abstract
Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/β-catenin, transforming growth factor-β (TNF-β), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.
Collapse
|
|
6
|
Significance of Micromorphological Characteristics and Expression of Intermediate Filament Proteins CK7 and CK20 in the Differential Diagnosis of Serrated Lesions of the Colorectum. GASTROENTEROLOGY INSIGHTS 2023. [DOI: 10.3390/gastroent14010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/03/2023] Open
Abstract
Serrated lesions in the colorectum include all epithelial neoplastic lesions, which show a sawtooth-like morphology in the epithelial crypts. Classification systems nosologically divide colon serrated polyps into three different categories, primarily emphasizing their micromorphological growth pattern and cytodifferentiation: (1) hyperplastic polyps, (2) sessile serrated adenomas/polyps and (3) traditional serrated adenomas. Overall, 109 patients with serrated lesions of the colon, who underwent endoscopic or surgical polypectomy/tumorectomy during one or multiple endoscopic or surgical interventions, over a four-year period, were analyzed. The average age of patients was 62.8 ± 11.6 years. The frequency of serrated lesions of the colon in male patients was 2.4 times higher than in females (70.6% vs. 29.4%). All sessile serrated lesions without dysplasia were positive for CK7 and statistically significant compared to other serrated lesions, if this positivity was present in the complete crypt (p = 0.005). CK20 positivity, which is limited to the upper half of the crypt, is a special feature of hyperplastic polyps compared to other serrated lesions, which is statistically significant (p = 0.0078). Whereas, CK20 positivity of complete crypts is a statistically significant feature of traditional serrated adenomas (p < 0.01). Differences in the expression pattern of cytokeratin 7 and 20 in different serrated lesions may indicate different pathways of colorectal carcinogenesis, and be diagnostically and prognostically useful.
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel) 2021; 13:cancers13092025. [PMID: 33922197 PMCID: PMC8122718 DOI: 10.3390/cancers13092025] [Citation(s) in RCA: 404] [Impact Index Per Article: 101.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 02/07/2023] Open
Abstract
This review article contains a concise consideration of genetic and environmental risk factors for colorectal cancer. Known risk factors associated with colorectal cancer include familial and hereditary factors and lifestyle-related and ecological factors. Lifestyle factors are significant because of the potential for improving our understanding of the disease. Physical inactivity, obesity, smoking and alcohol consumption can also be addressed through therapeutic interventions. We also made efforts to systematize available literature and data on epidemiology, diagnosis, type and nature of symptoms and disease stages. Further study of colorectal cancer and progress made globally is crucial to inform future strategies in controlling the disease's burden through population-based preventative initiatives.
Collapse
|
|
9
|
Ahmad R, Singh JK, Wunnava A, Al-Obeed O, Abdulla M, Srivastava SK. Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review). Int J Mol Med 2021; 47:14. [PMID: 33655327 PMCID: PMC7834960 DOI: 10.3892/ijmm.2021.4847] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer‑related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, out of which 53,200 individuals would succumb to the disease in the USA alone in 2020. CRC‑related mortality ranks third among both males and females in the USA. CRC arises from 3 major pathways: i) The adenoma‑carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer. With widespread CRC screening, the incidence and mortality from CRC have decreased in developed countries. However, over the past few decades, CRC cases and mortality have been on the rise in young adults (age, <50 years). In addition, CRC cases are increasing in developing countries with a low gross domestic product (GDP) due to lifestyle changes. CRC is an etiologically heterogeneous disease classified by tumor location and alterations in global gene expression. Accumulating genetic and epigenetic perturbations and aberrations over time in tumor suppressor genes, oncogenes and DNA mismatch repair genes could be a precursor to the onset of colorectal cancer. CRC can be divided as sporadic, familial, and inherited depending on the origin of the mutation. Germline mutations in APC and MLH1 have been proven to play an etiological role, resulting in the predisposition of individuals to CRC. Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis. Timely detection and effective precision therapies based on the present knowledge of CRC is essential for successful treatment and patient survival. The present review presents the CRC incidence, risk factors, dysregulated signaling pathways and targeted therapies.
Collapse
Affiliation(s)
- Rehan Ahmad
- Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia
| | - Jaikee Kumar Singh
- Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan 303007, India
| | - Amoolya Wunnava
- Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan 303007, India
| | - Omar Al-Obeed
- Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia
| | - Maha Abdulla
- Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia
| | | |
Collapse
|
|
10
|
Booth AL, Taggart MW, Ono Y, Gonzalez RS. From Mixed Hyperplastic/Adenomatous Polyp to Sessile Serrated Lesion: A Long and Winding Road for Long and Winding Crypts. Arch Pathol Lab Med 2020; 145:1289-1296. [PMID: 33351878 DOI: 10.5858/arpa.2020-0591-ra] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— During the past 3 decades, numerous articles in the literature have offered terminology, diagnostic criteria, and consensus recommendations regarding the entity currently referred to by the World Health Organization as sessile serrated lesion. Given the many names and various, variably reproducible diagnostic criteria ascribed to sessile serrated lesion, confusion persists for many pathologists and gastroenterologists regarding the diagnosis. This distinction is important, as sessile serrated lesion can progress to malignancy, unlike its main differential diagnosis, hyperplastic polyp. Research studies have shed light on the characteristic architecture and morphology, immunohistochemical patterns, and molecular alterations of sessile serrated lesion, and multiple consensus meetings around the globe have developed their criteria and nomenclature, often clashing or mixing terms. OBJECTIVE.— To provide a narrative review from the entity's early description to our current understanding. DATA SOURCES.— The existing scientific and clinical literature, published texts, medical society recommendations, and specialty consensus guidelines. CONCLUSIONS.— The current World Health Organization criteria are a distillation of this scientific process, but terminology is still a point of contention worldwide.
Collapse
Affiliation(s)
- Adam L Booth
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Melissa W Taggart
- The Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston (Taggart)
| | - Yuho Ono
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Raul S Gonzalez
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| |
Collapse
|
|
11
|
Hyperplastic polyp or sessile serrated lesion? The contribution of serial sections to reclassification. Diagn Pathol 2020; 15:140. [PMID: 33298116 PMCID: PMC7726909 DOI: 10.1186/s13000-020-01057-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/29/2020] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The histological discrimination of hyperplastic polyps from sessile serrated lesions can be difficult. Sessile serrated lesions and hyperplastic polyps are types of serrated polyps which confer different malignancy risks, and surveillance intervals, and are sometimes difficult to discriminate. Our aim was to reclassify previously diagnosed hyperplastic polyps as sessile serrated lesions or confirmed hyperplastic polyps, using additional serial sections. METHODS Clinicopathological data for all colorectal hyperplastic polyps diagnosed in 2016 and 2017 was collected. The slides were reviewed and classified as hyperplastic polyps, sessile serrated lesion, or other, using current World Health Organization criteria. Eight additional serial sections were performed for the confirmed hyperplastic polyp group and reviewed. RESULTS Of an initial 147 hyperplastic polyps from 93 patients, 9 (6.1%) were classified as sessile serrated lesions, 103 as hyperplastic polyps, and 35 as other. Of the 103 confirmed hyperplastic polyps, 7 (6.8%) were proximal, and 8 (7.8%) had a largest fragment size of ≥5 mm and < 10 mm. After 8 additional serial sections, 11 (10.7%) were reclassified as sessile serrated lesions. They were all less than 5 mm and represented 14.3% of proximal polyps and 10.4% of distal polyps. An average of 3.6 serial sections were required for a change in diagnosis. CONCLUSION Histopathological distinction between hyperplastic polyps and sessile serrated lesions remains a challenge. This study has uncovered a potential role for the use of additional serial sections in the morphological reappraisal of small hyperplastic polyps, especially when proximally located.
Collapse
|
|
12
|
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.
Collapse
|
|
13
|
Nguyen LH, Goel A, Chung DC. Pathways of Colorectal Carcinogenesis. Gastroenterology 2020; 158:291-302. [PMID: 31622622 PMCID: PMC6981255 DOI: 10.1053/j.gastro.2019.08.059] [Citation(s) in RCA: 278] [Impact Index Per Article: 55.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 08/13/2019] [Accepted: 08/15/2019] [Indexed: 12/15/2022]
Abstract
Colorectal cancer is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alterations. We review the genetic changes associated with the development of precancerous colorectal adenomas and their progression to tumors, as well as the effects of defective DNA repair, chromosome instability, microsatellite instability, and alterations in the serrated pathway and DNA methylation. We provide insights into the different molecular subgroups of colorectal tumors that develop via each of these different mechanisms and their associations with patient outcomes.
Collapse
Affiliation(s)
- Long H Nguyen
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Ajay Goel
- Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Dallas, Texas; Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas; Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.
| | - Daniel C Chung
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Center for Cancer Risk Assessment, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
| |
Collapse
|
|
14
|
The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer. Cancers (Basel) 2019; 11:cancers11071017. [PMID: 31330830 PMCID: PMC6678087 DOI: 10.3390/cancers11071017] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 07/15/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional serrated adenomas/polyps. Serrated polyps are characterized by genetic (BRAF or KRAS mutations) and epigenetic (CpG island methylator phenotype (CIMP)) alterations that cooperate to initiate and drive malignant transformation from normal colon mucosa to polyps, and then to CRC. The high heterogeneity of the serrated lesions renders their diagnostic and pathological interpretation difficult. Hence, novel genetic and epigenetic biomarkers are required for better classification and management of CRCs. To date, several molecular alterations have been associated with the serrated polyp-CRC sequence. In addition, the gut microbiota is emerging as a contributor to/modulator of the serrated pathway. This review summarizes the state of the art of the genetic, epigenetic and microbiota signatures associated with serrated CRCs, together with their clinical implications.
Collapse
|
|
15
|
Nouraie M, Ashktorab H, Atefi N, Azam S, Tarjoman T, Lee E, Shokrani B, Afsari A, Soleimani A, Laiyemo AO, Singh S, Brim H. Can the rate and location of sessile serrated polyps be part of colorectal Cancer disparity in African Americans? BMC Gastroenterol 2019; 19:77. [PMID: 31126232 PMCID: PMC6534887 DOI: 10.1186/s12876-019-0996-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 05/16/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Up to 30% of colorectal cancers develop through the serrated pathway. African Americans (AAs) suffer a disproportionate burden of colorectal cancer. The aim of this study was to evaluate clinicopathological features of AA patients diagnosed with sessile serrated polyps (SSPs). METHODS We conducted a retrospective study of all colonoscopies (n = 12,085) performed at Howard University Hospital, from January 1st, 2010 to December 31st, 2015, of which 83% were in AA patients, (n = 10,027). Among AAs, pathology reports confirmed 4070 patients with polyps including 252 with SSPs. Demographic and clinical variables (i.e. sex, age, BMI, anatomic location, clinical symptoms, polyp size, and clinical indications were collected at colonoscopy. RESULTS In the AA population, the median age was 56 with interquartile range (IQR) of 51 to 62 years, 54% were female, and 48% had a BMI > 30. The most common reason for colonoscopy was screening (53%), whereas the prevalent reasons for diagnostic colonoscopies were changes in bowel habits (18%) and gastrointestinal bleeding (17%). The total number of SSPs among the 252 AA (diagnosed with SSPs) was 338. Of these, 9% (n = 29/338) had some degree of cytological dysplasia, primarily in the ascending colon (n = 6/42, 14%), Transverse colon (n = 2/16, 13%) and rectosigmoid (n = 19/233, 8%). About 24% of patients had more than 2 polyps. Most patients (76%) had distal SSPs (rectal and rectosigmoid), in comparison to 14% of proximal polyps and 10% of bilateral locations. Median SSA/P size for all locations was 0.6 cm. CONCLUSION The prevalence of SSPs accounts for 6% of all polyps in AA patients and was diagnosed in 2.5% of all colonoscopies (n = 252/10,027), which is higher than Caucasians in the US. SSPs were predominantly located in the left side, as compared to published literature showing the predominance in the right side of the colon. Screening of CRC will have the chance to detect high risk SSA/P in this population.
Collapse
Affiliation(s)
- Mehdi Nouraie
- University of Pittsburg, Medical center, Pittsburg, PA, USA.
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, USA.
| | - Hassan Ashktorab
- Department of Medicine, College of Medicine, Washington, DC, USA.
- Cancer Research Center and Department of Medicine, Howard University College of Medicine, 2041 Georgia Avenue, Washington, D.C, N.W., 20060, USA.
| | - Nazli Atefi
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Saman Azam
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Taraneh Tarjoman
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Edward Lee
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Babak Shokrani
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Ali Afsari
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| | - Akbar Soleimani
- Department of Medicine, College of Medicine, Washington, DC, USA
| | | | - Sanmeet Singh
- Department of Medicine, College of Medicine, Washington, DC, USA
| | - Hassan Brim
- Pathology Department, Cancer Center, College of Medicine, Washington, DC, USA
| |
Collapse
|
|
16
|
Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management. Gastroenterol Res Pract 2019; 2019:9179718. [PMID: 30774654 PMCID: PMC6350577 DOI: 10.1155/2019/9179718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023] Open
Abstract
Prompt diagnosis and correct management of the so called "serrated lesions" (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
Collapse
|
|
17
|
Lian H, Jia X, Shi N, Xie S, Wang J, Wang W, Ma F, Liu H, Wang A, Cheng X, Liu C. Notch signaling promotes serrated neoplasia pathway in colorectal cancer through epigenetic modification of EPHB2 and EPHB4. Cancer Manag Res 2018; 10:6129-6141. [PMID: 30538561 PMCID: PMC6257864 DOI: 10.2147/cmar.s178126] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background Dysregulation of erythropoietin-producing hepatoma (Eph) proteins in human cancers is extensively documented but not clear in colorectal cancer (CRC). In this study, we aimed to investigate the role of Notch signaling pathway and epigenetic modification of EPHB2 and EPHB4 expression in serrated neoplasia development. Methods The expression of EPHB2 and EPHB4 in CRC clinical specimens and cell lines were determined by immunohistochemistry, Western blot, and real-time PCR. Cell proliferation and invasion were evaluated by MTT and chamber kits, luciferase assay and co-immunoprecipitation were used to detect the transcriptional regulation and protein-protein interactions, respectively. The immunofluorescence assay was employed to confirm the subcellular location of Notch intracellular domain (NICD), and chromatin immunoprecipitation assay was implied to detect the modification types of H3K4me3 and H3K27me3. Mice xenograft model was used to detect the in vivo effects of EPHB2 and EPHB4 genes on cell growth. Results In CRC clinical specimens and cell lines, we found that EPHB2 was significantly decreased, while EPHB4 was elevated in the CRC tissues, and these aberrant expression manners correlated with worse overall survival rates in the clinic. When the EPHB2 and EPHB4 expressions were manipulated by overexpression or knockdown in the SW620 cells, the cell proliferation and invasion were obviously suppressed, whereas EPHB2 knockdown or EPHB4 overexpression showed the opposite phenotypes. We also found that Notch signaling pathway was abnormally activated and treatment of Notch signaling ligand human Jagged1 peptide downregulated EPHB2 and upregulated EPHB4 in the SW620 cells, as well as promoted the chromatin modification protein Jumonji domain-containing protein-3 (JMJD3) cytonuclear trans-localization with the NICD, which indicated that NICD brought JMJD3 to the EPHB4 enhancer region to decrease the H3K27me3 level. Conclusion Taken together, we provide a new mechanistic option in understanding the role of Notch signaling and the roles of EPHB2 and EPHB4 in CRC.
Collapse
Affiliation(s)
- Haifeng Lian
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Xingfang Jia
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Ning Shi
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Shuyang Xie
- Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, China
| | - Jian Wang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Wei Wang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Fengzhen Ma
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Haiyan Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Aili Wang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| | - Xiankui Cheng
- Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Chengxia Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China,
| |
Collapse
|
|
18
|
Kim SY, Kim TI. Serrated neoplasia pathway as an alternative route of colorectal cancer carcinogenesis. Intest Res 2018; 16:358-365. [PMID: 30090034 PMCID: PMC6077295 DOI: 10.5217/ir.2018.16.3.358] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 01/10/2023] Open
Abstract
In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes. With increasing information of the morphologic and molecular features of serrated lesions, one major challenge is how to reflect this knowledge in clinical practice, such as pathologic and endoscopic diagnosis, and guidelines for treatment and surveillance.
Collapse
Affiliation(s)
- Soon Young Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
19
|
Factors Associated With Classification of Hyperplastic Polyps as Sessile Serrated Adenomas/Polyps on Morphologic Review. J Clin Gastroenterol 2018; 52:524-529. [PMID: 28723863 DOI: 10.1097/mcg.0000000000000840] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Distinguishing sessile serrated adenomas/polyp (SSA/P), a subset of serrated polyps, from hyperplastic polyps (HPs) remains a challenge and has surveillance implications. Our goal was to identify clinical and pathologic factors associated with serrated polyps originally read as HPs being reassessed as SSA/Ps versus confirmed as HPs. METHODS Data were collected from consecutive patients with a right-sided HP and a corresponding comparison group with conventional adenomas between 1993 and 2003. Two experienced gastrointestinal pathologists, blinded to polyp and clinical factors, reinterpreted the HPs using current SSA/P classification criteria. These HPs were classified as SSA/P when diagnostic histologic feature(s) were present in at least 3 crypts. Analyses, conducted on a per polyp basis, examined the factors associated with risk of individual HPs being reassessed as SSA/Ps as opposed to being confirmed as HPs. RESULTS Of the 702 HPs (355 adults), 188 (26.8%) were reclassified as SSA/Ps. Predictors of HPs being reinterpreted as SSA/Ps included: size ≥5 mm [odds ratio (OR), 2.09; 95% confidence interval (CI), 1.34-3.26], proximal location (OR, 2.83; 95% CI, 1.69-4.74), synchronous adenomas with advanced pathology (OR, 2.61; 95% CI, 1.22-5.55) and ≥1 synchronous HPs (other than HP being reassessed) reclassified as SSA/Ps (OR, 11.76; 95% CI, 6.75-20.49). CONCLUSIONS Because HP versus SSP is not very reproducible the predictors of SSA/P that we identified, including size, location, and synchronous lesions, can offer some additional help to endoscopists when determining surveillance intervals in patients with serrated polyps. In addition, observed association between SSA/P with advanced conventional neoplasia (but not low-grade adenomas) suggests 2 distinct groups of patient predisposition, one with both advanced conventional and important serrated precursors (SSA/P) and the other largely restricted to nonadvanced conventional adenomas and HPs only. Whether the association reported here has to do with SSA/P diagnosis per se or generally larger size of SSA/P remains to be determined in future studies.
Collapse
|
|
20
|
Ma MX, Bourke MJ. Sessile Serrated Adenomas: How to Detect, Characterize and Resect. Gut Liver 2018; 11:747-760. [PMID: 28494577 PMCID: PMC5669590 DOI: 10.5009/gnl16523] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 12/06/2016] [Indexed: 12/13/2022] Open
Abstract
Serrated polyps are important contributors to the burden of colorectal cancers (CRC). These lesions were once considered to have no malignant potential, but currently up to 30% of all CRC are recognized to arise from the serrated neoplasia pathway. The primary premalignant lesions are sessile serrated adenomas/polyps (SSA/Ps), although traditional serrated adenomas are relatively uncommon. Compared to conventional adenomas, SSA/Ps are morphologically subtle with indistinct borders, may be difficult to detect endoscopically, are more prevalent than previously thought, are associated with synchronous and metachronous advanced neoplasia, and have a higher risk of incomplete resection. Although many lesions remain “dormant,” progressive disease is associated with the development of dysplasia and more rapid progression to CRC. As a result, SSA/Ps are strongly implicated in the development of interval cancers. These factors represent unique challenges that require a meticulous approach to their management. In this review, we summarize the contemporary literature on the characterization, detection and resection of SSA/Ps.
Collapse
Affiliation(s)
- Michael X Ma
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia
| | - Michael J Bourke
- Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia.,University of Sydney, Sydney, Australia
| |
Collapse
|
|
21
|
Borowsky J, Dumenil T, Bettington M, Pearson SA, Bond C, Fennell L, Liu C, McKeone D, Rosty C, Brown I, Walker N, Leggett B, Whitehall V. The role of APC in WNT pathway activation in serrated neoplasia. Mod Pathol 2018; 31:495-504. [PMID: 29148535 DOI: 10.1038/modpathol.2017.150] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 09/14/2017] [Accepted: 09/15/2017] [Indexed: 02/07/2023]
Abstract
Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively. WNT pathway activation was seen to a lesser extent in serrated pathway lesions. It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001). However, unlike the conventional pathway, truncating APC mutations were rare in the serrated pathway lesions especially sessile serrated adenomas even when dysplastic (15%) and in the BRAF mutant cancers with microsatellite instability that arise from them (8%). In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%). We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis. Moderate impact APC mutations and non-APC-related causes of increased WNT signaling may have a more important role in serrated neoplasia than the truncating APC mutations common in conventional adenomas.
Collapse
Affiliation(s)
- Jennifer Borowsky
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.,School of Medicine, The University of Queensland, Brisbane, QLD, Australia.,Envoi Specialist Pathologists, Kelvin Grove, Brisbane, QLD, Australia
| | - Troy Dumenil
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia
| | - Mark Bettington
- Envoi Specialist Pathologists, Kelvin Grove, Brisbane, QLD, Australia
| | - Sally-Ann Pearson
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia
| | - Catherine Bond
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia
| | - Lochlan Fennell
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia
| | - Cheng Liu
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.,School of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Diane McKeone
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia
| | - Christophe Rosty
- Envoi Specialist Pathologists, Kelvin Grove, Brisbane, QLD, Australia
| | - Ian Brown
- Envoi Specialist Pathologists, Kelvin Grove, Brisbane, QLD, Australia.,Pathology Queensland, Queensland Health, Brisbane, QLD, Australia
| | - Neal Walker
- Envoi Specialist Pathologists, Kelvin Grove, Brisbane, QLD, Australia
| | - Barbara Leggett
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.,School of Medicine, The University of Queensland, Brisbane, QLD, Australia.,Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Vicki Whitehall
- Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research Berghofer, Brisbane, QLD, Australia.,School of Medicine, The University of Queensland, Brisbane, QLD, Australia.,Pathology Queensland, Queensland Health, Brisbane, QLD, Australia
| |
Collapse
|
|
22
|
Gourevitch RA, Rose S, Crockett SD, Morris M, Carrell DS, Greer JB, Pai RK, Schoen RE, Mehrotra A. Variation in Pathologist Classification of Colorectal Adenomas and Serrated Polyps. Am J Gastroenterol 2018; 113:431-439. [PMID: 29380819 PMCID: PMC6049074 DOI: 10.1038/ajg.2017.496] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 10/15/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Endoscopist quality measures such as adenoma detection rate (ADR) and serrated polyp detection rates (SPDRs) depend on pathologist classification of histology. Although variation in pathologic interpretation is recognized, we add to the literature by quantifying the impact of pathologic variability on endoscopist performance. METHODS We used natural language processing to abstract relevant data from colonoscopy and related pathology reports performed over 2 years at four clinical sites. We quantified each pathologist's likelihood of classifying polyp specimens as adenomas or serrated polyps. We estimated the impact on endoscopists' ADR and SPDR of sending their specimens to pathologists with higher or lower classification rates. RESULTS We observed 85,526 colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which were analyzed by 48 pathologists. There was greater variation across pathologists in classification of serrated polyps than in classification of adenomas. We estimate the endoscopist's average SPDR would be 0.5% if all their specimens were analyzed by the pathologist in our sample with the lowest classification rate and 12.0% if all their specimens were analyzed by the pathologist with the highest classification rate. In contrast, the endoscopist's average ADR would be 28.5% and 42.4% if their specimens were analyzed by the pathologist with lowest and highest classification rate, respectively. CONCLUSIONS There is significant variation in pathologic interpretation, which more substantially affects endoscopist SPDR than ADR.
Collapse
Affiliation(s)
| | | | - Seth D. Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Michele Morris
- Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA
| | - David S. Carrell
- Kaiser Permanente of Washington Health Research Institute (formerly Group Health Research Institute), Seattle, WA
| | - Julia B. Greer
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Reetesh K. Pai
- Department of Pathology, UPMC Presbyterian Hospital, Pittsburgh, PA
| | - Robert E. Schoen
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Ateev Mehrotra
- Harvard Medical School, Boston MA
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA
| |
Collapse
|
|
23
|
Krishn SR, Kaur S, Sheinin YM, Smith LM, Gautam SK, Patel A, Jain M, Juvvigunta V, Pai P, Lazenby AJ, Roy HK, Batra SK. Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance. Oncotarget 2018; 8:7025-7038. [PMID: 27705923 PMCID: PMC5351688 DOI: 10.18632/oncotarget.12347] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Accepted: 09/20/2016] [Indexed: 12/23/2022] Open
Abstract
Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.
Collapse
Affiliation(s)
- Shiv Ram Krishn
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Yuri M Sheinin
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Lynette M Smith
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shailendra K Gautam
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Asish Patel
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Vasthala Juvvigunta
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Priya Pai
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Audrey J Lazenby
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Hemant K Roy
- Department of Gastroenterology, Boston Medical Center, Boston, Massachusetts, USA
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.,Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.,Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA
| |
Collapse
|
|
24
|
Park SJ, Yoon H, Jung IS, Shin CM, Park YS, Kim NY, Lee DH. Clinical outcomes of surveillance colonoscopy for patients with sessile serrated adenoma. Intest Res 2018; 16:134-141. [PMID: 29422808 PMCID: PMC5797260 DOI: 10.5217/ir.2018.16.1.134] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 05/03/2017] [Accepted: 05/07/2017] [Indexed: 01/09/2023] Open
Abstract
Background/Aims Sessile serrated adenomas (SSAs) are known to be precursors of colorectal cancer (CRC). The proper interval of follow-up colonoscopy for SSAs is still being debated. We sought to determine the proper interval of colonoscopy surveillance in patients diagnosed with SSAs in South Korea. Methods We retrospectively reviewed the medical records of patients diagnosed with SSAs who received 1 or more follow-up colonoscopies. The information reviewed included patient baseline characteristics, SSA characteristics, and colonoscopy information. Results From January 2007 to December 2011, 152 SSAs and 8 synchronous adenocarcinomas were identified in 138 patients. The mean age of the patients was 62.2 years and 60.1% patients were men. SSAs were located in the right colon (i.e., from the cecum to the hepatic flexure) in 68.4% patients. At the first follow-up, 27 SSAs were identified in 138 patients (right colon, 66.7%). At the second follow-up, 6 SSAs were identified in 65 patients (right colon, 66.7%). At the 3rd and 4th follow-up, 21 and 11 patients underwent colonoscopy, respectively, and no SSAs were detected. The total mean follow-up duration was 33.9 months. The mean size of SSAs was 8.1±5.0 mm. SSAs were most commonly found in the right colon (126/185, 68.1%). During annual follow-up colonoscopy surveillance, no cancer was detected. Conclusions Annual colonoscopy surveillance is not necessary for identifying new CRCs in all patients diagnosed with SSAs. In addition, the right colon should be examined more carefully because SSAs occur more frequently in the right colon during initial and follow-up colonoscopies.
Collapse
Affiliation(s)
- Sung Jae Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - In Sub Jung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Na Young Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| |
Collapse
|
|
25
|
Anderson JC, Butterly LF, Robinson CM, Weiss JE, Amos C, Srivastava A. Risk of Metachronous High-Risk Adenomas and Large Serrated Polyps in Individuals With Serrated Polyps on Index Colonoscopy: Data From the New Hampshire Colonoscopy Registry. Gastroenterology 2018; 154:117-127.e2. [PMID: 28927878 PMCID: PMC5742054 DOI: 10.1053/j.gastro.2017.09.011] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 09/08/2017] [Accepted: 09/12/2017] [Indexed: 01/26/2023]
Abstract
BACKGROUND & AIMS Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies. METHODS We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs. RESULTS HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP. CONCLUSIONS In an analysis of data from a population-based colonoscopy registry, we found index large SP or index STSA with no index HRA increased risk of metachronous large SPs but not metachronous HRA. HRA and synchronous SPs at index colonoscopy significantly increased risk of metachronous HRA. Individuals with HRA and synchronous large SP or any STSA could therefore benefit from close surveillance.
Collapse
Affiliation(s)
- Joseph C. Anderson
- Department of Veterans Affairs Medical Center, White River Junction, VT and The Geisel School of Medicine at Dartmouth, Hanover NH
| | - Lynn F. Butterly
- Dartmouth Hitchcock Medical Center, Section of Gastroenterology, Lebanon, NH,The Geisel School of Medicine at Dartmouth, Department of Community and Family Medicine, Hanover, NH
| | - Christina M. Robinson
- Dartmouth Hitchcock Medical Center, Section of Gastroenterology, Lebanon, NH,Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH
| | - Julia E. Weiss
- Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH,Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH
| | - Christopher Amos
- The Geisel School of Medicine at Dartmouth, Department of Community and Family Medicine, Hanover, NH,Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH,Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH
| | | |
Collapse
|
|
26
|
Changing pathological diagnosis from hyperplastic polyp to sessile serrated adenoma: systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017; 29:1327-1331. [PMID: 29049128 DOI: 10.1097/meg.0000000000000994] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The WHO published a new classification of colonic polyps in 2010, including the group of serrated polyps, which can be divided into hyperplastic polyps (HP), traditional serrated adenomas, and sessile serrated adenomas (SSA) or polyps. To assess the rate of re-diagnosis of HP to SSA and to look for possible predictors for changing the diagnosis. English Medical literature searches were performed for 'reassessment' OR 'reclassification' AND 'hyperplastic polyp' OR 'sessile serrated adenoma' till 31 January 2017. PRISMA guidelines for systematic reviews were followed. Studies that included a precise re-diagnosis of HP into SSA were included. We also looked for predictors of SSA diagnosis such as polyp location and size, patient sex and age, and synchronous advanced adenoma. Altogether, we found 220 eligible studies; 212 were excluded as they did not fulfill the inclusion criteria and we were left with eight studies including 2625 patients. The odds ratio for the number of polyps with changed pathological diagnosis from HP to SSA was 0.112 with 95% confidence interval (CI): 0.099-0.126 (P<0.0001) or 11.2%. Heterogeneity between studies was significant with Q=199.4, d.f. (Q)=9, P<0.0001, and I=95.486%. The odds ratio for changing the pathological diagnosis from HP to SSA for polyp proximal location and polyp size more than 5 mm were 4.401, 95% CI: 2.784-6.958, P<0.0001, and 8.336, 95% CI: 4.963-15.571, P<0.0001, respectively. Endoscopists and pathologists should be aware of the SSA diagnosis when finding HPs larger than 5 mm in the right colon. The diagnosis of HP in these cases should be reassessed by experienced gastrointestinal pathologists.
Collapse
|
|
27
|
IJspeert JEG, Bevan R, Senore C, Kaminski MF, Kuipers EJ, Mroz A, Bessa X, Cassoni P, Hassan C, Repici A, Balaguer F, Rees CJ, Dekker E. Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview. Gut 2017; 66:1225-1232. [PMID: 26911398 DOI: 10.1136/gutjnl-2015-310784] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 12/14/2015] [Accepted: 01/16/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. METHODS Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. RESULTS Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. CONCLUSIONS The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.
Collapse
Affiliation(s)
- J E G IJspeert
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - R Bevan
- Department of Gastroenterology and Hepatology, South Tyneside District Hospital, South Shields, UK
| | - C Senore
- Department of Gastroenterology and Hepatology, Piemonte Reference Centre for Epidemiology and Cancer Prevention, Turin, Italy
| | - M F Kaminski
- Department of Gastroenterological Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Medical Centre for Postgraduate Education, Warsaw, Poland.,Institute of Health and Society, University of Oslo, Oslo, Norway
| | - E J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - A Mroz
- Department of Gastroenterology, Hepatology and Oncology, Medical Centre for Postgraduate Education, Warsaw, Poland
| | - X Bessa
- Department of Gastroenterology, Digestive Service, Hospital del Mar de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - P Cassoni
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - C Hassan
- Department of Gastroenterology and Hepatology, 'Nuovo regina Margherita' Hospital, Rome, Italy
| | - A Repici
- Department of Gastroenterology and Hepatology, Humanitas Research Hospital, Humanitas University, Milan, Italy
| | - F Balaguer
- Department of Gastroenterology, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - C J Rees
- Department of Gastroenterology and Hepatology, South Tyneside District Hospital, South Shields, UK
| | - E Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
28
|
IJspeert JEG, Madani A, Overbeek LIH, Dekker E, Nagtegaal ID. Implementation of an e-learning module improves consistency in the histopathological diagnosis of sessile serrated lesions within a nationwide population screening programme. Histopathology 2017; 70:929-937. [DOI: 10.1111/his.13155] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 11/19/2016] [Accepted: 12/18/2016] [Indexed: 01/16/2023]
Affiliation(s)
- Joep E G IJspeert
- Department of Gastroenterology and Hepatology; Academic Medical Centre; Amsterdam The Netherlands
| | - Ariana Madani
- Foundation PALGA (the nationwide network and registry of histo- and cytopathology in the Netherlands); Houten The Netherlands
- Department of Gastroenterology and Hepatology; Erasmus University Medical Centre; Rotterdam The Netherlands
| | - Lucy I H Overbeek
- Foundation PALGA (the nationwide network and registry of histo- and cytopathology in the Netherlands); Houten The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology; Academic Medical Centre; Amsterdam The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology; Radboud University Medical Centre; Nijmegen The Netherlands
| |
Collapse
|
|
29
|
IJspeert JEG, Rana SAQ, Atkinson NSS, van Herwaarden YJ, Bastiaansen BAJ, van Leerdam ME, Sanduleanu S, Bisseling TM, Spaander MCW, Clark SK, Meijer GA, van Lelyveld N, Koornstra JJ, Nagtegaal ID, East JE, Latchford A, Dekker E. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut 2017; 66:278-284. [PMID: 26603485 DOI: 10.1136/gutjnl-2015-310630] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 09/23/2015] [Accepted: 10/28/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.
Collapse
Affiliation(s)
- J E G IJspeert
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - S A Q Rana
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - N S S Atkinson
- Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Y J van Herwaarden
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - B A J Bastiaansen
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - M E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - S Sanduleanu
- Division of Gastroenterology and Hepatology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - T M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - M C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - S K Clark
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - G A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - N van Lelyveld
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - J J Koornstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - J E East
- Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - A Latchford
- The Polyposis Registry, St Mark's Hospital, London, UK
| | - E Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | | |
Collapse
|
|
30
|
Rau T. [Pathogenetic aspects in precursor lesions of gastrointestinal tumors]. DER PATHOLOGE 2016; 37:186-190. [PMID: 27638535 DOI: 10.1007/s00292-016-0220-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The pathogenesis of precursor lesions of gastrointestinal tumors is manifested in many ways. In the esophagus an aberrant genetic expression of intestinal transcription factors, such as CDX2 is initiated by local environment factors. During the subsequent dysplasia to carcinoma sequence, chromosomal gain and loss of genes occurs. A 4-color fluorescence in situ hybridization (FISH) assay can be applied in dysplasia as well as in Barrett's adenocarcinoma to define prognostic marker combinations. In the gastric carcinogenesis sequence the gene expression of CDX1 is regulatively dependent on an interplay between inflammation and promotor methylation. In the colon sessile serrated adenomas show a sequence with initial BRAF mutation and late onset of MLH1 promotor hypermethylation with consecutive potential cancer progression. This event is accompanied by an increase of intraepithelial lymphocytes, which is an easy to use tool for routine diagnostics using H&E sections. Next generation sequencing (NGS) investigations of germline mutations in colorectal cancer revealed a spectrum of mutations with low penetration in the field of mismatch repair proteins as well as the APC gene. An individual risk stratification for penetration of these germline mutations is necessary. In conclusion, genetics, phenotypes and terminology of gastrointestinal precursor lesions are unified to a mutually influencing concept within medicine.
Collapse
Affiliation(s)
- T Rau
- Pathologisches Institut, Universitätsklinikum Erlangen, Erlangen, Deutschland. .,Institut für Pathologie, Universität Bern, Murtenstr. 31, 3010, Bern, Schweiz.
| |
Collapse
|
|
31
|
Silva P, Albuquerque C, Lage P, Fontes V, Fonseca R, Vitoriano I, Filipe B, Rodrigues P, Moita S, Ferreira S, Sousa R, Claro I, Nobre Leitão C, Chaves P, Dias Pereira A. Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities. Int J Mol Med 2016; 38:687-702. [PMID: 27430658 PMCID: PMC4990292 DOI: 10.3892/ijmm.2016.2666] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 03/11/2016] [Indexed: 12/25/2022] Open
Abstract
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0×10−7), in most early lesions. Proximal/whole-colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatel-lite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2×10−4; 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress.
Collapse
Affiliation(s)
- Patrícia Silva
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Cristina Albuquerque
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Pedro Lage
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Vanessa Fontes
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Ricardo Fonseca
- Pathology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Inês Vitoriano
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Bruno Filipe
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Paula Rodrigues
- Familial Cancer Risk Clinic, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Susana Moita
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Sara Ferreira
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Rita Sousa
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Isabel Claro
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Carlos Nobre Leitão
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Paula Chaves
- Pathology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - António Dias Pereira
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| |
Collapse
|
|
32
|
Seo JY, Choi SH, Chun J, Lee C, Choi JM, Jin EH, Hwang SW, Im JP, Kim SG, Kim JS. Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas. Intest Res 2016; 14:270-9. [PMID: 27433150 PMCID: PMC4945532 DOI: 10.5217/ir.2016.14.3.270] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 09/21/2015] [Accepted: 10/02/2015] [Indexed: 02/06/2023] Open
Abstract
Background/Aims The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. Methods Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. Results Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. Conclusions Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy.
Collapse
Affiliation(s)
- Ji Yeon Seo
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Seung Ho Choi
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Jaeyoung Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Changhyun Lee
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Ji Min Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Hyo Jin
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Sung Wook Hwang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
33
|
Mirzaie AZ, Khakpour H, Mireskandari M, Shayanfar N, Fatahi L. Investigating The Frequency of Serrated Polyps/Adenomas and Their Subtypes in Colonic Polyp Samples. Med Arch 2016; 70:198-202. [PMID: 27594746 PMCID: PMC5010071 DOI: 10.5455/medarh.2016.70.198-202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 03/25/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The purpose of this study was to determine the frequency of Serrated polyps of colonic polyps samples in Hazrat_e Rasoul_e Akram Hospital over ten years. MATERIALS The target group in this study was patients with colonic polyps in Hazrat_e Rasoul_e Akram Hospital. Pathologic evaluation of these patients was done. Serrated polyps, by location, gender, age and type of polyps were divided and frequency of them were determined separately. RESULTS Of 381 patients studied, 224 (58.79%) and 157(41.20%) were males and females, respectively. Mean age of patients was 59.25 years. In initial diagnosis, frequency of Adenomatous polyp, Hyperplastic polyp and Mixed polyp were 92.44% and 5.33%, and 2.22%, respectively. In final diagnosis (Second evaluation), frequency of Adenomatous polyp, Hyperplastic polyp, Mixed polyp, Sessile Serrated Adenoma/ Polyp, Traditional Serrated Adenoma and SPU (Serrated Polyp Unclassifiable) were 90.44%, 4.88%, 2.44%, 1.11%, 0.66% and 0.44%, respectively. 72.13% and 27.86% of polyps were low grade dysplasia and high grade dysplasia, respectively. According to the results of this study, the incidence of all types of polyps detected was more in men than women. Rectum and sigmoid were most abundant in the area polyp in both initial and final diagnosis. CONCLUSION Despite the low prevalence of Serrated polyps in patients, early diagnosis is the best action to reduce morbidity and mortality. Probability of the risk of progression from low grade to high grade dysplasia and transforming into Adenocarcinoma is high in Serrated polyps.
Collapse
Affiliation(s)
- Ali Zare Mirzaie
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
| | - Hakimeh Khakpour
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
| | | | - Nasrin Shayanfar
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
| | - Ladan Fatahi
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
34
|
Schachschal G, Sehner S, Choschzick M, Aust D, Brandl L, Vieth M, Wegscheider K, Baretton GB, Kirchner T, Sauter G, Rösch T. Impact of reassessment of colonic hyperplastic polyps by expert GI pathologists. Int J Colorectal Dis 2016; 31:675-83. [PMID: 26847619 DOI: 10.1007/s00384-016-2523-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/27/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recommended follow-up intervals after endoscopic removal of hyperplastic polyps (HP) and sessile serrated adenomas (SSA) differ because of assumed differences in biological behaviour. However, histopathologic differentiation is difficult, with higher SSA rates reported from specialist GI histopathologists. OBJECTIVE The objective of this study was to clarify the relevance of histologic reassessment of HP. DESIGN AND SETTING From a prospective screening colonoscopy study relevant serrated lesions (excluding distal small HP ≤5 mm) diagnosed by private practice pathologists were reassessed by four specialized GI pathologists PATIENTS One thousand sixty-nine screening colonoscopies were performed in patients. MAIN OUTCOME MEASUREMENTS In terms of main outcome measurements, there is a likelihood of changes of the HP diagnosis on reassessment, as well as interrater variability. RESULTS SSA were initially diagnosed in 7 cases (0.7%) and relevant HP in 83 (7.8%; 101 lesions). Of the latter, the chance of a change in diagnosis from HP to SSA by any of the four specialist histopathologists was higher for larger (>5 mm) and right-sided lesions (19.1 vs 1.3%, OR 18.4, p = 0.04) including a higher likelihood to change recommended follow-up intervals (32.1 vs 3.3%, p < 0.01). However, follow-up intervals were determined by concomitant adenomas in 41%. Interrater variability was also higher for these lesions (p = 0.04), with an overall kappa value of 0.48. However, this issue related to only 1.2% of the 1069 study cases. LIMITATION The limitations this study are the limited case number as well as limited retrospective assessment. CONCLUSIONS Right-sided HP >5 mm had a higher chance of change in diagnosis to SSA; therefore, they should probably be treated like adenomas and be removed. However, reliable data for recommendations on follow-up intervals of HP or SSA will require follow-up studies.
Collapse
Affiliation(s)
- Guido Schachschal
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Martinistr 52, 20246, Hamburg, Germany
| | - Susanne Sehner
- Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Matthias Choschzick
- Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.,Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland
| | - Daniela Aust
- Department of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Lydia Brandl
- Institute of Pathology, Ludwig-Maximilian University, Munich, Germany
| | - Michael Vieth
- Institute of Pathology, Bayreuth Hospital, Bayreuth, Germany
| | - Karl Wegscheider
- Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Gustavo B Baretton
- Department of Pathology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Thomas Kirchner
- Institute of Pathology, Ludwig-Maximilian University, Munich, Germany
| | - Guido Sauter
- Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Martinistr 52, 20246, Hamburg, Germany.
| |
Collapse
|
|
35
|
|
|
36
|
Chino A, Yamamoto N, Kato Y, Morishige K, Ishikawa H, Kishihara T, Fujisaki J, Ishikawa Y, Tamegai Y, Igarashi M. The frequency of early colorectal cancer derived from sessile serrated adenoma/polyps among 1858 serrated polyps from a single institution. Int J Colorectal Dis 2016; 31:343-9. [PMID: 26510850 DOI: 10.1007/s00384-015-2416-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). METHODS A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. RESULTS Among 1160 HP lesions, 1 (0.1%) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7%) high-grade dysplasia (HGD/Tis) and 1 (0.2%) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1%) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16%) HGD/Tis and 1 (2%) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5%) HGD/Tis and 166 (1%) T1 cancers were identified. CONCLUSIONS Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1%) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype.
Collapse
Affiliation(s)
- A Chino
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan.
| | - N Yamamoto
- Division of Pathology, The Cancer Institute of Japanese Foundation of Cancer Research, Tokyo, Japan
| | - Y Kato
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
- Division of Pathology, The Cancer Institute of Japanese Foundation of Cancer Research, Tokyo, Japan
| | - K Morishige
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
| | - H Ishikawa
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
| | - T Kishihara
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
- Division of Pathology, The Cancer Institute of Japanese Foundation of Cancer Research, Tokyo, Japan
| | - J Fujisaki
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
| | - Y Ishikawa
- Division of Pathology, The Cancer Institute of Japanese Foundation of Cancer Research, Tokyo, Japan
| | - Y Tamegai
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
| | - M Igarashi
- Department Digestive Endoscopy, The Cancer Institution Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan
| |
Collapse
|
|
37
|
Serrated colorectal polyps in inflammatory bowel disease. Mod Pathol 2015; 28:1584-93. [PMID: 26403785 DOI: 10.1038/modpathol.2015.111] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Revised: 08/14/2015] [Accepted: 08/15/2015] [Indexed: 01/09/2023]
Abstract
Serrated colorectal polyps, which, besides hyperplastic polyps, comprise sessile serrated adenomas/polyps and traditional serrated adenomas, are presumptive precursors of at least 20% of sporadic colorectal carcinomas; however, their significance in patients with inflammatory bowel disease is unclear. We retrospectively evaluated 78 serrated polyps, removed over a 14-year period from 6602 inflammatory bowel disease patients undergoing endoscopic surveillance, with respect to morphologic, clinicopathologic, and molecular features, and compared rates of advanced neoplasia (high-grade dysplasia and carcinoma) development following the index serrated polyp diagnosis to reference inflammatory bowel disease cohorts without serrated polyps. Serrated polyps negative for dysplasia, which morphologically resembled sporadic sessile serrated adenoma/polyps, occurred mainly in females, in the proximal colon, and contained BRAF mutations. Serrated polyps with low-grade dysplasia resembled sporadic traditional serrated adenomas and occurred mainly in males, in the distal colon, and contained KRAS mutations. Serrated polyps indefinite for dysplasia were morphologically heterogeneous, but similar to serrated polyps positive for low-grade dysplasia with respect to male predominance, left-sided location, and KRAS mutation rates. Rates of prevalent neoplasia associated with serrated polyps positive for low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia were 76, 39, and 11%, respectively (P<0.001). Actuarial 10-year rates of incident advanced neoplasia after an initial diagnosis of serrated polyp positive for low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia were 17, 8, and 0%, respectively, the first and last being significantly different (P=0.02) and comparable to those of corresponding reference populations of inflammatory bowel disease patients with and without low-grade dysplasia at baseline, respectively. We conclude that in serrated polyps from inflammatory bowel disease patients, dysplasia grade correlates with morphology, sex, anatomic location, BRAF and KRAS mutation status, prevalent conventional neoplasia, and rates of advanced neoplasia development.
Collapse
|
|
38
|
Liu FT, Ou-Yang X, Zhang GP, Luo HL. Progress in research of colorectal intraepithelial neoplasia and adenoma. Shijie Huaren Xiaohua Zazhi 2015; 23:3413-3420. [DOI: 10.11569/wcjd.v23.i21.3413] [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] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is a common malignant tumor in the digestive system, and the early diagnosis of colorectal cancer has been the focus of its prevention and control. Colorectal intraepithelial neoplasia and adenoma are considered to be the most important precancerous lesions of colorectal cancer. In recent years, with the development of biological medicine, genetics,
and other disciplines, many studies have explored the relationship between intraepithelial neoplasia and adenoma and colorectal cancer, and some new research progress has been achieved to provide some guidance for the future clinical screening, regular follow-up and chemical prevention. However, it remains to be studied how colorectal intraepithelial neoplasia and adenoma form and evolve to colorectal cancer.
Collapse
|
|
39
|
Abstract
Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding pathogenesis and clinical behaviour. Four decades ago, the adenoma-carcinoma pathway was presented as the main pathway towards CRC, a conclusion that was largely based on evidence from observational morphological studies. This concept was later substantiated at the genomic level. Over the past decade, evidence has been generated for alternative routes in which CRC might develop, in particular the serrated neoplasia pathway. Providing indisputable evidence for the neoplastic potential of serrated polyps has been difficult. Reasons include the absence of reliable longitudinal observations on individual serrated lesions that progress to cancer, a shortage of available animal models for serrated lesions and challenging culture conditions when generating organoids of serrated lesions for in vitro studies. However, a growing body of circumstantial evidence has been accumulated, which indicates that ≥15% of CRCs might arise through the serrated neoplasia pathway. An even larger amount of post-colonoscopy colorectal carcinomas (carcinomas occurring within the surveillance interval after a complete colonoscopy) have been suggested to originate from serrated polyps. The aim of this Review is to assess the current status of the serrated neoplasia pathway in CRC and highlight clinical implications.
Collapse
|
|
40
|
East JE, Vieth M, Rex DK. Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance. Gut 2015; 64:991-1000. [PMID: 25748647 DOI: 10.1136/gutjnl-2014-309041] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 02/12/2015] [Indexed: 12/13/2022]
Affiliation(s)
- James E East
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, Indiana, USA
| |
Collapse
|
|
41
|
Bateman AC, Shepherd NA. UK guidance for the pathological reporting of serrated lesions of the colorectum. J Clin Pathol 2015; 68:585-91. [PMID: 25934843 DOI: 10.1136/jclinpath-2015-203016] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 04/13/2015] [Indexed: 11/04/2022]
Abstract
Bowel cancer screening programmes have highlighted to endoscopists and clinicians the spectrum of serrated colorectal lesions. One of the most significant developments has been the recognition that sessile serrated lesions (SSLs), while bearing histological resemblance to hyperplastic polyps (HPs), may be associated with the enhanced development of epithelial dysplasia and colorectal adenocarcinoma. Different minimum criteria exist for the diagnosis of SSLs and their differentiation from HPs. Furthermore, the spectrum of terminology used to describe the entire range of serrated lesions is wide. This variability has impaired interobserver agreement during their histopathological assessment. Here, we provide guidance for the histopathological reporting of serrated lesions, including a simplified nomenclature system. Essentially, we recommend use of the following terms: HP, SSL, SSL with dysplasia, traditional serrated adenoma (TSA) and mixed polyp. It is hoped that this standardisation of nomenclature will facilitate studies of the biological significance of serrated lesions in terms of the relative risk of disease progression.
Collapse
Affiliation(s)
- Adrian C Bateman
- Department of Cellular Pathology, Southampton General Hospital, Southampton, UK
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, UK
| |
Collapse
|
|
42
|
Serrated polyps and their alternative pathway to the colorectal cancer: a systematic review. Gastroenterol Res Pract 2015; 2015:573814. [PMID: 25945086 PMCID: PMC4405010 DOI: 10.1155/2015/573814] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 03/20/2015] [Accepted: 03/22/2015] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. For a long time, only one pathway of colorectal carcinogenesis was known. In recent years, a new “alternative” pathway through serrated adenoma was described. Recent meta-analysis estimated these cancers as about 10% to 30% of all CRCs. Serrated polyps are the second most popular groups of polyps (after conventional adenomas) found during colonoscopy. Serrated polyps of the colon are clinically and molecularly diverse changes that have common feature as crypt luminal morphology characterized by glandular serration. Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy. Understanding of the so-called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC.
Collapse
|
|
43
|
Ban S, Mitomi H, Horiguchi H, Sato H, Shimizu M. Adenocarcinoma arising in small sessile serrated adenoma/polyp (SSA/P) of the colon: clinicopathological study of eight lesions. Pathol Int 2014; 64:123-32. [PMID: 24698422 DOI: 10.1111/pin.12147] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 02/16/2014] [Indexed: 12/12/2022]
Abstract
We reviewed the clinicopathological findings of eight cases of sessile serrated adenoma/polyps (SSA/Ps) with carcinoma, the largest diameter of which was 10 mm or less. All lesions were polyps located in the right side of the colon. Four lesions showed submucosal invasion and one lesion invaded the proper muscle layer. The depth of invasion, however, did not seem to be related to the carcinoma area size. Most carcinomas were well to moderately differentiated tubular adenocarcinomas focally showing some serrated appearances, and the predominant component of one carcinoma was a poorly differentiated medullary growth with inflammatory stroma. Rapid progression to invasive carcinoma from SSA/P was suggested for the carcinoma with proper muscle invasion whereas one submucosally invasive carcinoma was considered to progress over 7 years. Immunohistochemically, it was suggested that with or without hMLH1 protein loss, alterations of p53 and/or Wnt signaling pathway can be involved in the cancerization through SSA/Ps. The carcinomas irregularly imitated the mucin expression of the SSA/Ps (positive for MUC5AC and MUC2, and MUC6 expression in crypt bases), which was lost with progression of the carcinomas. Analyses of small SSA/P lesions with cancerization would facilitate the understanding of the mode of progression of SSA/Ps and their early detection.
Collapse
Affiliation(s)
- Shinichi Ban
- Department of Pathology, Saiseikai Kawaguchi General Hospital, Kawaguchi, Japan
| | | | | | | | | |
Collapse
|
|
44
|
Tsai JH, Liau JY, Lin YL, Lin LI, Cheng YC, Cheng ML, Jeng YM. Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis. Mod Pathol 2014; 27:1375-85. [PMID: 24603588 DOI: 10.1038/modpathol.2014.35] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 12/16/2013] [Accepted: 12/17/2013] [Indexed: 12/12/2022]
Abstract
Traditional serrated adenoma is one type of colorectal serrated neoplasm and a precursor of colorectal cancer. We evaluated the pathologic and molecular features of 60 traditional serrated adenomas with cytologic dysplasia and/or invasive carcinoma. On the basis of morphological features, 16 cases (27%) were categorized as traditional serrated adenoma with serrated dysplasia and 25 cases (42%) as traditional serrated adenoma with conventional adenomatous dysplasia. In addition, 19 cases (31%) showed an overall tubulovillous adenomatous structure but with focal serrated feature. Traditional serrated adenoma with serrated dysplasia had a significantly higher frequency of BRAF mutation than traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature (P=0.006), whereas traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature had higher frequencies of KRAS mutation than traditional serrated adenoma with serrated dysplasia (P<0.0001). Only traditional serrated adenoma with serrated dysplasia showed sessile serrated adenoma-like lesions at the periphery (n=3) and developed invasive carcinomas when the lesions were <15 mm in size. Abnormal nuclear accumulation of β-catenin was detected in traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature but not in traditional serrated adenoma with serrated dysplasia. The frequency of the positive CpG island methylator phenotype was similar among the three dysplastic subtypes, and immunostaining of four mismatch repair proteins in the nucleus was retained in all traditional serrated adenomas and associated invasive malignancies. Traditional serrated adenoma-associated adenocarcinomas (n=28) displayed distinctive morphological features: oval cell nuclei, serrated glands, infiltrating borders, rare occurrences of necrosis and mucinous differentiation. Overexpression of p53 was detected only in high-grade dysplasia and invasive adenocarcinoma. Our findings indicate that traditional serrated adenoma is a heterogeneous neoplasm with two pathways of neoplastic progression, which are distinct from the sessile serrated pathway of colorectal carcinogenesis.
Collapse
Affiliation(s)
- Jia-Huei Tsai
- 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jau-Yu Liau
- 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Lin Lin
- 1] Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Liang-In Lin
- 1] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan [2] Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chen Cheng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Ling Cheng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yung-Ming Jeng
- 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
45
|
Kang YK. Diminutive and Small Colorectal Polyps: The Pathologist's Perspective. Clin Endosc 2014; 47:404-8. [PMID: 25324998 PMCID: PMC4198555 DOI: 10.5946/ce.2014.47.5.404] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 07/05/2014] [Indexed: 01/09/2023] Open
Abstract
Recent progress in advanced endoscopic imaging and electronic chromoendoscopy allows the real-time endoscopic estimation of the histologic type of polyps, mainly for the differentiation of adenomas from hyperplastic polyps. Accordingly, a "resect-and-discard" strategy applied to diminutive colorectal polyps is now one of the emerging issues among gastroenterologists. The strategy has a practical advantage in terms of the potential cost savings. However, it has a number of limitations in the medical, academic, and legal aspects. The major pitfalls include the endoscopic investigation of colorectal polyps with a wide variety of histogenetic origins, including serrated polyps, and the lack of a standardized method for polyp size measurement. Another issue is the importance of the pathologic diagnosis for legal purposes and medical research. Moreover, it is not certain whether the implementation of the strategy has economic benefit in countries with an undervalued reimbursement system for pathologic examination. There is no doubt that a highly confident optical diagnosis of polyp type is a novel valuable tool. It can provide a more steady symbiosis between gastroenterologists and pathologists to allow a more evident diagnosis and management of patients with colorectal polyps.
Collapse
Affiliation(s)
- Yun Kyung Kang
- Department of Pathology, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| |
Collapse
|
|
46
|
Xiang L, Zhan Q, Zhao XH, Wang YD, An SL, Xu YZ, Li AM, Gong W, Bai Y, Zhi FC, Liu SD. Risk factors associated with missed colorectal flat adenoma: A multicenter retrospective tandem colonoscopy study. World J Gastroenterol 2014; 20:10927-10937. [PMID: 25152596 PMCID: PMC4138473 DOI: 10.3748/wjg.v20.i31.10927] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 03/19/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the miss rate for colorectal flat adenomas during colonoscopy and the risk factors.
METHODS: Flat adenomas are frequently missed during colonoscopy. However, the risk factors that influence their miss rates are unclear. This was a multicenter, retrospective study in which patients diagnosed with colorectal adenomas at a diagnostic colonoscopy and followed within 3 mo by a second therapeutic colonoscopy were pooled out from the established database. The “per-patient” and “per-adenoma” adenoma miss rates (AMR) for overall adenomas and flat adenomas, and patient-, adenoma-, and procedure-related risk factors potentially associated with the “per-adenoma” AMR for flat adenomas were determined.
RESULTS: Chromoscopy and high-definition colonoscopy were not taken under consideration in the study. Among 2093 patients with colorectal adenomas, 691 (33.0%) were diagnosed with flat adenomas, 514 with concomitant protruding adenomas and 177 without. The “per-patient” AMR for flat adenomas was 43.3% (299/691); the rates were 54.3% and 11.3%, respectively, for those with protruding adenomas and those without (OR = 9.320, 95%CI: 5.672-15.314, χ2 = 99.084, P < 0.001). The “per-adenoma” AMR for flat adenomas was 44.3% (406/916). In multivariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller adenoma size, location at the right colon, insufficient experience of the colonoscopist, and withdrawal time < 6 min were associated with an increased “per-adenoma” AMR for flat adenomas. The AMR for flat adenomas was moderately correlated with that for overall adenomas (r = 0.516, P < 0.0001). The AMR for flat adenomas during colonoscopy was high.
CONCLUSION: Patient’s age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the “per-adenoma” AMR for flat adenomas.
Collapse
|
|
47
|
Intermediate serrated polyp as an intermediate lesion of hyperplastic polyp and sessile serrated polyp/adenoma in terms of morphological and molecular features. Hum Pathol 2014; 45:1759-65. [DOI: 10.1016/j.humpath.2014.04.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Revised: 04/17/2014] [Accepted: 04/18/2014] [Indexed: 01/13/2023]
|
|
48
|
DNA methylation alterations of AXIN2 in serrated adenomas and colon carcinomas with microsatellite instability. BMC Cancer 2014; 14:466. [PMID: 24964857 PMCID: PMC4099028 DOI: 10.1186/1471-2407-14-466] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Accepted: 06/16/2014] [Indexed: 12/12/2022] Open
Abstract
Background Recent work led to recognize sessile serrated adenomas (SSA) as precursor to many of the sporadic colorectal cancers with microsatellite instability (MSI). However, comprehensive analyses of DNA methylation in SSA and MSI cancer have not been conducted. Methods With an array-based methylation sensitive amplified fragment length polymorphism (MS-AFLP) method we analyzed 8 tubular (TA) and 19 serrated (SSA) adenomas, and 14 carcinomas with (MSI) and 12 without (MSS) microsatellite instability. MS-AFLP array can survey relative differences in methylation between normal and tumor tissues of 9,654 DNA fragments containing all NotI sequences in the human genome. Results Unsupervised clustering analysis of the genome-wide hypermethylation alterations revealed no major differences between or within these groups of benign and malignant tumors regardless of their location in intergenic, intragenic, promoter, or 3′ end regions. Hypomethylation was less frequent in SSAs compared with MSI or MSS carcinomas. Analysis of variance of DNA methylation between these four subgroups identified 56 probes differentially altered. The hierarchical tree of this subset of probes revealed two distinct clusters: Group 1, mostly composed by TAs and MSS cancers with KRAS mutations; and Group 2 with BRAF mutations, which consisted of cancers with MSI and MLH1 methylation (Group 2A), and SSAs without MLH1 methylation (Group 2B). AXIN2, which cooperates with APC and β-catenin in Wnt signaling, had more methylation alterations in Group 2, and its expression levels negatively correlated with methylation determined by bisulfite sequencing. Within group 2B, low and high AXIN2 expression levels correlated significantly with differences in size (P = 0.01) location (P = 0.05) and crypt architecture (P = 0.01). Conclusions Somatic methylation alterations of AXIN2, associated with changes in its expression, stratify SSAs according to some clinico-pathological differences. We conclude that hypermethylation of MLH1, when occurs in an adenoma cell with BRAF oncogenic mutational activation, drives the pathway for MSI cancer by providing the cells with a mutator phenotype. AXIN2 inactivation may contribute to this tumorigenic pathway either by mutator phenotype driven frameshift mutations or by epigenetic deregulation contemporary with the unfolding of the mutator phenotype.
Collapse
|
|
49
|
Pritchard S, Haboubi N. Serrated polyps: managing expanding science or scientific management of an expanding entity? Colorectal Dis 2014; 16:403-5. [PMID: 24835776 DOI: 10.1111/codi.12629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Sue Pritchard
- Department of Histopathology, University Hospital of South Manchester, Manchester, UK
| | | |
Collapse
|
|
50
|
Gerola S, Nittka S, Kähler G, Tao S, Brenner H, Binelli G, Eils R, Brors B, Neumaier M. Genetic variants in apoptosis-related genes associated with colorectal hyperplasia. Genes Chromosomes Cancer 2014; 53:769-78. [DOI: 10.1002/gcc.22185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 04/21/2014] [Indexed: 12/13/2022] Open
Affiliation(s)
- Stefano Gerola
- Institute for Clinical Chemistry; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim 68167 Germany
| | - Stefanie Nittka
- Institute for Clinical Chemistry; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim 68167 Germany
| | - Georg Kähler
- Department of Medical; Medical Center Mannheim, Universitätsmedizin Mannheim, University of Heidelberg; Mannheim Germany
| | - Sha Tao
- Division of Clinical Epidemiology and Aging Research; German Cancer Research Center (DKFZ); Heidelberg 69120 Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research; German Cancer Research Center (DKFZ); Heidelberg 69120 Germany
| | - Giorgio Binelli
- Department of Theoretical and Applied Sciences; Insubria University; Varese Italy
| | - Roland Eils
- Division of Theoretical Bioinformatics; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224; Heidelberg Germany
| | - Benedikt Brors
- Division of Theoretical Bioinformatics; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224; Heidelberg Germany
| | - Michael Neumaier
- Institute for Clinical Chemistry; Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg; Mannheim 68167 Germany
| |
Collapse
|