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1
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Ali M, Srour L, Bitar M, Karam K, El Hajj II, Fiani E. Current Guidelines and Advances in the Management of Fundic Gland Polyps. J Gastroenterol Hepatol 2025. [PMID: 40259438 DOI: 10.1111/jgh.16972] [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] [Received: 10/24/2024] [Revised: 01/23/2025] [Accepted: 04/03/2025] [Indexed: 04/23/2025]
Abstract
Fundic gland polyps (FGPs) are the most common type of gastric polyps, predominantly benign and associated with long-term proton pump inhibitor (PPI) use and familial adenomatous polyposis (FAP). FGPs are primarily found in the gastric fundus and body, with higher prevalence in individuals over 50 and previously thought to have been a consequence of prolonged PPI therapy. Although most FGPs are sporadic and carry minimal malignancy risk, FAP-associated FGPs may exhibit dysplastic changes, warranting closer surveillance. This review provides a comprehensive overview of the current guidelines and recent advances in the management of FGPs, focusing on diagnostic approaches, including endoscopic and imaging techniques, as well as histopathological evaluation. It discusses the pathophysiology of FGP formation, highlighting the role of PPI use, the inverse relationship with Helicobacter pylori infection, and the genetic alterations in the APC and β-catenin genes. Recommendations for the management of FGPs vary by patient population; for those with FAP or on long-term PPI therapy, surveillance strategies include endoscopic monitoring and possible polypectomy in cases of dysplasia. For most patients with sporadic FGPs, conservative management is appropriate. This review aims to provide clarity on the management of FGPs, emphasizing the need for individualized approaches based on risk factors and polyp characteristics.
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Affiliation(s)
- Majed Ali
- Department of Internal Medicine, University of Balamand, Beirut, Lebanon
| | - Lynn Srour
- Department of Internal Medicine, University of Balamand, Beirut, Lebanon
| | - Mustapha Bitar
- Department of Internal Medicine, University of Balamand, Beirut, Lebanon
| | - Karam Karam
- Department of Gastroenterology, University of Balamand, Beirut, Lebanon
| | - Ihab I El Hajj
- Department of Gastroenterology, University of Balamand, Beirut, Lebanon
| | - Elias Fiani
- Department of Gastroenterology, University of Balamand, Beirut, Lebanon
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Bouchiba H, Aelvoet AS, van Grieken NCT, Brosens LAA, Bastiaansen BAJ, Dekker E. The challenge of preventing gastric cancer in patients under surveillance for familial adenomatous polyposis. Fam Cancer 2025; 24:14. [PMID: 39776297 PMCID: PMC11711555 DOI: 10.1007/s10689-024-00438-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/26/2024] [Indexed: 01/11/2025]
Abstract
Several extra-colonic manifestations, including duodenal polyposis and desmoid tumors, are well-described manifestations in familial adenomatous polyposis (FAP). More recently, an increase in gastric cancer diagnoses has been observed in FAP. This case series presents nine patients with FAP who were diagnosed with gastric cancer at our FAP expertise center, of whom eight were diagnosed between 2017 and 2023, while before 2017 the only diagnosis of gastric cancer was in 2001. Among the nine cases of gastric cancer, seven were located in the proximal stomach amidst carpeting fundic gland polyposis and two were located in the distal stomach. Despite ongoing advances in endoscopic technology, all patients were diagnosed during regular endoscopic surveillance, and six of the nine patients died within two years. We aim to raise awareness on gastric cancer risk in FAP patients and stress the urgent need of improved gastric surveillance strategies with timely detection of gastric cancer precursors.
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Affiliation(s)
- Hicham Bouchiba
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Arthur S Aelvoet
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Barbara A J Bastiaansen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Amsterdam, The Netherlands.
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3
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Shimamoto Y, Takeuchi Y, Ishiguro S, Nakatsuka SI, Yunokizaki H, Ezoe Y, Shichijo S, Maekawa A, Kanesaka T, Yamamoto S, Higashino K, Uedo N, Ishihara R, Mutoh M, Ishikawa H. Classification of fundic gland polyps for predicting gastric neoplasms in Helicobacter pylori-negative patients with familial adenomatous polyposis. Gastric Cancer 2024; 27:1311-1319. [PMID: 39172199 DOI: 10.1007/s10120-024-01539-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/13/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND In familial adenomatous polyposis (FAP) patients, fundic gland polyps (FGPs) have been considered a risk factor for gastric neoplasms. We speculated that FGPs in FAP patients spread directionally from the greater to the lesser curvature of the gastric body and investigated the relationship between the distribution of FGPs and gastric neoplasm development. METHODS We extracted 195 FAP patients from two institutions and reviewed their medical records. Gastric polyposis was classified based on the FGP distribution (P0, no FGPs; P1, localized in the fundus or greater curvature of the gastric body; P2, spreading to the anterior or posterior wall; P3, involving the proximal half of the lesser curvature; and P4, spreading from P3 to the anal side of the lesser curvature). RESULTS The 195 eligible patients were divided into the neoplasm group (n = 54, 28%) and the non-neoplasm group (n = 141, 72%). Overall, 24% of the patients were Helicobacter pylori (H. pylori)-positive. In the FGP distribution, the rate of patients with gastric neoplasm tended to increase significantly with each step towards an increasingly wide distribution from P0 to P4 in H. pylori-negative patients, but not in H. pylori-positive ones. In addition, in H. pylori-negative patients, the likelihood of neoplasm increased consistently from P0 to P4, with the highest odds ratio (95% confidence interval) at P4 of 14.1 (2.5-154.4). Furthermore, multivariate analysis showed P4 and Spigelman stage ≥III were significantly associated with gastric neoplasm development. CONCLUSION FGP distribution was correlated with gastric neoplasm development in FAP patients.
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Affiliation(s)
- Yusaku Shimamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
- Department of Genetic Oncology, Division of Hereditary Tumors, Osaka International Cancer Institute, Osaka, Japan.
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan.
| | | | - Shin-Ichi Nakatsuka
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | | | | | - Satoki Shichijo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Akira Maekawa
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Kanesaka
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Koji Higashino
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Michihiro Mutoh
- Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideki Ishikawa
- Ishikawa Gastroenterology Clinic, Osaka, Japan
- Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Kelly P, Lauwers GY. Polyps and tumour‐like lesions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:195-226. [DOI: 10.1002/9781119423195.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Azer SA. Dual primary gastric and colorectal cancer: The known hereditary causes and underlying mechanisms. World J Gastrointest Oncol 2024; 16:2264-2270. [PMID: 38994141 PMCID: PMC11236243 DOI: 10.4251/wjgo.v16.i6.2264] [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: 12/19/2023] [Revised: 03/03/2024] [Accepted: 04/07/2024] [Indexed: 06/13/2024] Open
Abstract
In this editorial, I commented on the paper by Lin et al, published in this issue of the World Journal of Gastrointestinal Oncology. The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer (CRC). The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer (GC) stage rather than the CRC stage. Although surveillance was recommended in the conclusion, the authors did not explore this area in their study and did not include tests used for such surveillance. This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs. These include hereditary diffuse GC, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, Lynch syndrome, and three major hamartomatous polyposis syndromes associated with CRC and GC, namely Peutz-Jeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome. Careful assessment of these syndromes/conditions, including inheritance, risk of gastric and colorectal or other cancer development, genetic mutations and recommended genetic investigations, is crucial for optimum management of these patients.
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Affiliation(s)
- Samy A Azer
- Medical Education and Medicine, King Saud University College of Medicine, Riyadh 11461, Saudi Arabia
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Lauricella S, Rausa E, Pellegrini I, Ricci MT, Signoroni S, Palassini E, Cavalcoli F, Pasanisi P, Colombo C, Vitellaro M. Current management of familial adenomatous polyposis. Expert Rev Anticancer Ther 2024; 24:363-377. [PMID: 38785081 DOI: 10.1080/14737140.2024.2344649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/15/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. AREAS COVERED The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. EXPERT OPINION FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
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Affiliation(s)
- Sara Lauricella
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Emanuele Rausa
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ilaria Pellegrini
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Teresa Ricci
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Stefano Signoroni
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elena Palassini
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Patrizia Pasanisi
- Nutrition Research and Metabolomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Chiara Colombo
- Sarcoma Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marco Vitellaro
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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7
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Gul MO, Oguz Aslayan S, Corbaci K, Selman A, Akcay EB, Unal Ozdemir Z, Ozdemir H, Akyuz C. Gastric Polyps Detected Incidentally during Gastroscopy and Follow-Up Results. J Clin Med 2024; 13:3117. [PMID: 38892828 PMCID: PMC11172658 DOI: 10.3390/jcm13113117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/20/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
(1) Background: We aimed to identify the possible relationship between various diseases of the upper digestive system and colon polyps by analyzing patients with gastric polyps and evaluating the cancers and diseases accompanying the polyps. (2) Methods: Each patient's age; gender; polyp type and size; presence of Helicobacter pylori (H. pylori), atrophic gastritis, and intestinal metaplasia; status of whether cancer developed during follow-up; status of whether a colonoscopy was performed or not; and colon pathologies detected during colonoscopy were analyzed retrospectively using hospital records. (3) Results: Between the study dates, 19,214 esophagogastroduodenoscopies were performed in the endoscopy unit of our hospital. Gastric polyps were detected in 178 (0.9%) patients. No significant relationship was found between the gastric polyp size and the occurrence of gastric cancer or gastrointestinal system malignancy (p > 0.05). A colonoscopy was performed in 86 of the 178 patients who underwent gastroscopy. The frequency of polyp detection during colonoscopy was statistically significantly higher in patients with gastric polyps than in patients without gastric polyps (p < 0.001). (4) Conclusions: New prospective studies are needed regarding the relationship between gastric polyps and gastrointestinal system diseases. Going forward, a colonoscopy will be required in gastric polyp patients, especially with FGP.
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Affiliation(s)
- Mehmet Onur Gul
- Surgical Oncology Clinic, Malatya Training and Research Hospital, Malatya 44330, Turkey
| | - Selda Oguz Aslayan
- General Surgery Department, Üsküdar State Hospital, Istanbul 34662, Turkey;
| | - Kadir Corbaci
- General Surgery Department, Osmaneli Mustafa Selahattin Çetintaş State Hospital, Bilecik 11500, Turkey;
| | - Aytac Selman
- General Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey; (A.S.); (E.B.A.); (Z.U.O.); (H.O.); (C.A.)
| | - Emre Berat Akcay
- General Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey; (A.S.); (E.B.A.); (Z.U.O.); (H.O.); (C.A.)
| | - Zehra Unal Ozdemir
- General Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey; (A.S.); (E.B.A.); (Z.U.O.); (H.O.); (C.A.)
| | - Hakan Ozdemir
- General Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey; (A.S.); (E.B.A.); (Z.U.O.); (H.O.); (C.A.)
| | - Cebrail Akyuz
- General Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey; (A.S.); (E.B.A.); (Z.U.O.); (H.O.); (C.A.)
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Ushiku T, Lauwers GY. Pathology and Clinical Relevance of Gastric Epithelial Dysplasia. Gastroenterol Clin North Am 2024; 53:39-55. [PMID: 38280750 DOI: 10.1016/j.gtc.2023.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2024]
Abstract
Gastric dysplasia is defined as an unequivocally neoplastic epithelium. Dysplastic lesions are characterized by cellular atypia reflective of abnormal differentiation and disorganized glandular architecture. The last few years have been marked by a refinement of the prognosis and risk of progression of gastric dysplasia and the recognition of novel morphologic patterns of dysplasia. Determination of the correct diagnosis and grade of dysplasia are critical steps since it will be predicting the risk of malignant transformation and help tailor appropriate surveillance strategy. This review describes the morphologic characteristics of conventional dysplasia and nonconventional gastric dysplasia that have been more recently characterized.
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Affiliation(s)
- Tetsuo Ushiku
- Department of Pathology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Gregory Y Lauwers
- Department of Pathology, Gastrointestinal Pathology Section, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, Tampa, FL 33612, USA; Departments of Pathology and Oncologic Sciences, Tampa, FL, USA.
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9
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Iwamuro M, Kawano S, Otsuka M. Differential Diagnoses and Management Approaches for Gastric Polyposis. GASTROENTEROLOGY INSIGHTS 2024; 15:122-144. [DOI: 10.3390/gastroent15010009] [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: 01/06/2025] Open
Abstract
Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-0082, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-0082, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-0082, Japan
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10
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Shimamoto Y, Takeuchi Y, Ishiguro S, Nakatsuka S, Yunokizaki H, Ezoe Y, Nakajima T, Tanaka K, Ishihara R, Takayama T, Yoshida T, Sugano K, Mutoh M, Ishikawa H. Genotype-phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis. Cancer Sci 2023; 114:4596-4606. [PMID: 37798255 PMCID: PMC10728006 DOI: 10.1111/cas.15945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/03/2023] [Accepted: 08/18/2023] [Indexed: 10/07/2023] Open
Abstract
Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype-phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398-1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
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Affiliation(s)
- Yusaku Shimamoto
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yoji Takeuchi
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Genetic Oncology, Division of Hereditary TumorsOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiJapan
| | | | - Shin‐ichi Nakatsuka
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | | | - Yasumasa Ezoe
- Medical Ethics and Medical Genetics, School of Public HealthKyoto UniversityKyotoJapan
| | - Takeshi Nakajima
- Medical Ethics and Medical Genetics, School of Public HealthKyoto UniversityKyotoJapan
| | - Kumiko Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Ryu Ishihara
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Teruhiko Yoshida
- Department of Genetic Medicine and ServicesNational Cancer Center HospitalTokyoJapan
| | - Kokichi Sugano
- Department of Genetic Medicine, Sasaki FoundationKyoundo HospitalTokyoJapan
| | - Michihiro Mutoh
- Department of Molecular‐Targeting Prevention, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Hideki Ishikawa
- Ishikawa Gastroenterology ClinicOsakaJapan
- Department of Molecular‐Targeting Prevention, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
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11
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McGowan KP, Delgado E, Keeley TM, Hibdon ES, Turgeon DK, Stoffel EM, Samuelson LC. Region-specific Wnt signaling responses promote gastric polyp formation in patients with familial adenomatous polyposis. JCI Insight 2023; 8:e174546. [PMID: 37943618 PMCID: PMC10896006 DOI: 10.1172/jci.insight.174546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/08/2023] [Indexed: 11/12/2023] Open
Abstract
Germline adenomatous polyposis coli (APC) mutation in patients with familial adenomatous polyposis (FAP) promotes gastrointestinal polyposis, including the formation of frequent gastric fundic gland polyps (FGPs). In this study, we investigated how dysregulated Wnt signaling promotes FGPs and why they localize to the corpus region of the stomach. We developed a biobank of FGP and surrounding nonpolyp corpus biopsies and organoids from patients with FAP for comparative studies. Polyp biopsies and polyp-derived organoids exhibited enhanced Wnt target gene expression. Polyp-derived organoids with intrinsically upregulated Wnt signaling showed poor tolerance to further induction, suggesting that high Wnt restricts growth. Targeted genomic sequencing revealed that most gastric polyps did not arise via APC loss of heterozygosity. Studies in genetic mouse models demonstrated that heterozygous Apc loss increased epithelial cell proliferation in the corpus but not the antrum, while homozygous Apc loss was not maintained in the corpus yet induced hyperproliferation in the antrum. Our findings suggest that heterozygous APC mutation in patients with FAP may be sufficient to drive polyp formation in the corpus region while subsequent loss of heterozygosity to further enhance Wnt signaling is not tolerated. This finding contextualizes the abundant yet benign nature of gastric polyps in FAP patient corpus compared with the rare, yet adenomatous polyps in the antrum.
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Affiliation(s)
| | | | | | | | - D. Kim Turgeon
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Elena M. Stoffel
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Linda C. Samuelson
- Department of Molecular & Integrative Physiology and
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
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12
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Varanese M, Lattina I, Frattaroli F, Assisi D, Sanchez-Mete L, Baldissone E, Lauro A, Stigliano V. Two Cases, Too Little, Too Late: Surveillance for Gastric Cancer in Patients with FAP. Dig Dis Sci 2023; 68:4117-4122. [PMID: 37713035 DOI: 10.1007/s10620-023-08097-8] [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] [Accepted: 06/06/2023] [Indexed: 09/16/2023]
Abstract
Familial adenomatous polyposis is an autosomal dominant disease due to a mutation in the adenomatous polyposis coli (APC) gene. The disease, characterized by the development of adenomas throughout the colon and rectum, is also associated with extracolonic manifestations including gastric fundic polyps and cancer. In this report, we describe two patients with FAP with advanced gastric adenocarcinoma who received systemic chemotherapy. We reviewed the literature published over the past two decades on gastric cancer in FAP patients to assess the clinical course of this disease. Due to its recent increased incidence in Western countries, close endoscopic surveillance to detect early gastric neoplastic lesions is recommended.
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Affiliation(s)
- Marzia Varanese
- Department of Surgical Sciences, Sapienza University, Rome, Italy
| | - Ilario Lattina
- Department of Surgical Sciences, Sapienza University, Rome, Italy.
| | | | - Daniela Assisi
- Gastroenterology & Digestive Endoscopy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Lupe Sanchez-Mete
- Gastroenterology & Digestive Endoscopy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Elena Baldissone
- Department of Surgical Sciences, Sapienza University, Rome, Italy
| | - Augusto Lauro
- Department of Surgical Sciences, Sapienza University, Rome, Italy
| | - Vittoria Stigliano
- Gastroenterology & Digestive Endoscopy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
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Sami AS, Sylvester FA, Attard T, Mir S. Fundic Gland Polyps: Strategizing a Surveillance Framework for Children and Adolescents. J Pediatr Gastroenterol Nutr 2023; 77:439-441. [PMID: 37440343 DOI: 10.1097/mpg.0000000000003891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/15/2023]
Affiliation(s)
- Ahmad Salah Sami
- From the Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Francisco A Sylvester
- From the Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Thomas Attard
- the Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Missouri School of Medicine, Children's Mercy Kansas City, Kansas City, MO
| | - Sabina Mir
- From the Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC
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14
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Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer 2023; 22:413-422. [PMID: 37119510 DOI: 10.1007/s10689-023-00334-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/18/2023] [Indexed: 05/01/2023]
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.
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Affiliation(s)
- J K Stone
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
| | - N A Mehta
- Center for Interventional and Therapeutic Endoscopy, Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
| | - H Singh
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada
| | - W El-Matary
- Section of Pediatric Gastroenterology, Department of Pediatrics, Max Rady College of Medicine, Winnipeg, MB, Canada
| | - C N Bernstein
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
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15
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Shimamoto Y, Takeuchi Y, Ishiguro S, Nakatsuka SI, Yunokizaki H, Ezoe Y, Matsuno K, Nakahira H, Shichijo S, Maekawa A, Kanesaka T, Yamamoto S, Higashino K, Uedo N, Ishihara R, Ishikawa H. Feasibility of underwater endoscopic mucosal resection for endoscopic management of gastric neoplasms in patients with familial adenomatous polyposis. Surg Endosc 2023; 37:6877-6884. [PMID: 37311890 DOI: 10.1007/s00464-023-10175-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 05/30/2023] [Indexed: 06/15/2023]
Abstract
BACKGROUND Underwater endoscopic mucosal resection (UEMR) has been developed as an effective endoscopic intervention for colon, rectum, and duodenum neoplasms. However, there are no comprehensive reports regarding the stomach, and its safety and efficacy are unknown. We aimed to examine the feasibility of UEMR for gastric neoplasms in patients with familial adenomatous polyposis (FAP). METHODS We retrospectively extracted data of patients with FAP who underwent endoscopic resection (ER) for gastric neoplasms at Osaka International Cancer Institute from February 2009 to December 2018. Elevated gastric neoplasms of ≤ 20 mm in diameter were extracted, and conventional endoscopic mucosal resection (CEMR) and UEMR were compared. Furthermore, outcomes after ER until March 2020 were examined. RESULTS 91 endoscopically resected gastric neoplasms were extracted from 31 patients with 26 pedigrees, and 12 neoplasms underwent CEMR and 25 neoplasms underwent UEMR was compared. The procedure time was shorter for UEMR than for CEMR. There was no significant difference between en bloc resection and R0 resection rates by EMR methods. CEMR and UEMR showed postoperative hemorrhage rates of 8% and 0%, respectively. Residual/local recurrent neoplasms were identified in four lesions (4%), but additional endoscopic intervention (three UEMR and one cauterization) resulted in a local cure. CONCLUSION UEMR was feasible in gastric neoplasms of FAP patients, especially in elevated lesions and those of ≤ 20 mm in diameter.
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Affiliation(s)
- Yusaku Shimamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan.
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
| | | | - Shin-Ichi Nakatsuka
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | | | | | - Kenshi Matsuno
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiroko Nakahira
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Satoki Shichijo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Akira Maekawa
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Takashi Kanesaka
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Koji Higashino
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-Ku, Osaka, 541-8567, Japan
| | - Hideki Ishikawa
- Ishikawa Gastroenterology Clinic, Osaka, Japan
- Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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16
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McGowan KP, Delgado E, Hibdon ES, Samuelson LC. Differential sensitivity to Wnt signaling gradients in human gastric organoids derived from corpus and antrum. Am J Physiol Gastrointest Liver Physiol 2023; 325:G158-G173. [PMID: 37338119 PMCID: PMC10393332 DOI: 10.1152/ajpgi.00092.2023] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 06/21/2023]
Abstract
Wnt signaling regulates gastric stem cell proliferation and differentiation. Although similar Wnt gradients exist within the corpus and antrum of the human stomach, there are striking differences in gland architecture and disease manifestation that suggest Wnt may differentially regulate progenitor cell function in each compartment. In this study, we tested sensitivities to Wnt activation in human gastric corpus and antral organoids to determine whether progenitor cells have region-specific differences in Wnt responsiveness. Human patient-matched corpus and antral organoids were grown in the presence of varying concentrations of the Wnt pathway activator CHIR99021 to assess regional sensitivity to Wnt signaling on growth and proliferation. Corpus organoids were further studied to understand how high Wnt affected cellular differentiation and progenitor cell function. A lower concentration of CHIR99021 stimulated peak growth in corpus organoids compared with patient-matched antral organoids. Supramaximal Wnt signaling levels in corpus organoids suppressed proliferation, altered morphology, reduced surface cell differentiation, and increased differentiation of deep glandular neck and chief cells. Surprisingly, corpus organoids grown in high CHIR99021 had enhanced organoid forming potential, indicating that progenitor cell function was maintained in these nonproliferative, deep glandular cell-enriched organoids. Passaging high-Wnt quiescent organoids into low Wnt rescued normal growth, morphology, and surface cell differentiation. Our findings suggest that human corpus progenitor cells have a lower threshold for optimal Wnt signaling than antral progenitor cells. We demonstrate that Wnt signaling in the corpus regulates a bimodal axis of differentiation, with high Wnt promoting deep glandular cell differentiation and suppressing proliferation while simultaneously promoting progenitor cell function.NEW & NOTEWORTHY This study demonstrates that human gastric corpus organoids have a lower Wnt signaling threshold to drive optimal growth relative to patient-matched antral organoids. Paradoxically, supramaximal Wnt levels suppress corpus organoid proliferation, yet promote differentiation toward deep glandular cell types while simultaneously enhancing progenitor cell function. These findings provide novel insights into how Wnt signaling differentially regulates homeostasis in the human gastric corpus and antrum and contextualizes patterns of Wnt activation diseases.
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Affiliation(s)
- Kevin P McGowan
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
| | - Elizabeth Delgado
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
| | - Elise S Hibdon
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
| | - Linda C Samuelson
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States
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17
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Garutti M, Foffano L, Mazzeo R, Michelotti A, Da Ros L, Viel A, Miolo G, Zambelli A, Puglisi F. Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool. Genes (Basel) 2023; 14:1025. [PMID: 37239385 PMCID: PMC10218093 DOI: 10.3390/genes14051025] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could be challenging because of a lack of validated testing criteria or because of their suboptimal performance. In addition, many clinicians are not sufficiently well trained to identify and select patients that could benefit from a genetic test. Herein, we searched the available literature to comprehensively review and categorize hereditary cancer syndromes affecting adults with the aim of helping clinicians in their daily clinical practice through a visual tool.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Lorenzo Foffano
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Roberta Mazzeo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Anna Michelotti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Lucia Da Ros
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alessandra Viel
- Unit of Oncogenetics and Genomics CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Gianmaria Miolo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alberto Zambelli
- Medical Oncology and Hematology Unit, IRCCS—Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
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18
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Akanuma N, Rabinovitch PS, Mattis AN, Lauwers GY, Choi WT. Fundic Gland Polyps Lack DNA Content Abnormality Characteristic of Other Adenomatous Precursor Lesions in the Gastrointestinal Tract. Mod Pathol 2023; 36:100117. [PMID: 36805791 DOI: 10.1016/j.modpat.2023.100117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/15/2023] [Accepted: 01/22/2023] [Indexed: 02/04/2023]
Abstract
Fundic gland polyps (FGPs) develop sporadically (frequently after proton pump inhibitor therapy) or in the setting of a hereditary polyposis syndrome, such as familial adenomatous polyposis (FAP). FAP-related FGPs often demonstrate low-grade dysplasia (LGD) and are frequently associated with APC mutations, even in the absence of dysplasia. Sporadic FGPs with dysplasia are molecularly similar to FAP-related FGPs and demonstrate frequent mutations in APC gene. Despite having similar molecular alterations with colorectal and other adenomatous precursor lesions in the gastrointestinal (GI) tract, FGPs rarely progress to advanced gastric neoplasia (high-grade dysplasia [HGD] or adenocarcinoma), and their role in gastric tumorigenesis remains unclear but likely limited. The clinicopathologic features of 192 patients diagnosed with FGPs, including 86 with FAP-related FGPs (33 with dysplastic FGPs and 53 with nondysplastic FGPs) and 106 with sporadic FGPs (12 with dysplastic FGPs and 94 with nondysplastic FGPs), were analyzed. DNA flow cytometry was performed on 111 FAP-related FGP biopsies, including 32 FGPs with LGD and 79 nondysplastic FGPs, to assess the presence of abnormal DNA content (ie, aneuploidy or elevated 4N fraction). Moreover, 40 sporadic FGP biopsies, including 14 dysplastic (13 LGD and 1 HGD) and 26 nondysplastic FGPs, were examined for DNA content abnormality. Patients with FAP and nondysplastic FGPs were more likely to be younger (mean age, 32 years) and present with multiple FGPs (92%, defined as having ≥2 FGPs) than those with sporadic nondysplastic FGPs (61 years and 65%, respectively; P < .001). They also recorded higher rates of previous or concurrent gastric epithelial dysplasia not occurring in a FGP (8%, P = .016), nongastric GI dysplasia (96%, P < .001), and nongastric GI malignancy (17%, P = .001) compared with those with sporadic nondysplastic FGPs (0%, 52%, and 2%, respectively). The sporadic group was more frequently associated with proton pump inhibitor therapy (78%, P < .001), gastric intestinal metaplasia (24%, P = .004), and a family history of gastric cancer (10%, P = .027) than the FAP group (19%, 6%, and 0%, respectively). Almost all FAP-related FGPs had a polypoid endoscopic appearance (98% vs 84% for sporadic FGPs; P = .009). The mean size of the largest FAP-related FGPs (0.5 cm) was similar to that of sporadic FGPs (0.7 cm) (P = .069). None of the 147 patients with FAP-related or sporadic nondysplastic FGPs were associated with subsequent detection of advanced gastric neoplasia within a mean follow-up time of 54 months (range, <1 to 277 months). However, 2 (4%) of the 45 patients with FAP-related or sporadic dysplastic FGPs developed advanced gastric neoplasia within a mean follow-up time of 59 months (range, <1 to 236 months). One (3%) of the 33 patients with FAP and dysplastic FGPs developed signet ring cell adenocarcinoma, whereas 1 (8%) of the 12 patients with sporadic dysplastic FGPs developed HGD (P = .445). However, none of the FAP-related and sporadic FGP biopsies, regardless of the presence or absence of dysplasia, demonstrated DNA content abnormality. In conclusion, FGPs lack large-scale chromosomal changes that are characteristic of the typical adenoma-carcinoma sequence involved in the development of other GI malignancies. Progression to advanced gastric neoplasia is rare in FGPs, which may be partly explained by the apparent lack of the chromosomal instability phenotype in these lesions.
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Affiliation(s)
- Naoki Akanuma
- Department of Pathology, University of California at San Francisco, San Francisco, California
| | - Peter S Rabinovitch
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington
| | - Aras N Mattis
- Department of Pathology, University of California at San Francisco, San Francisco, California
| | - Gregory Y Lauwers
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Won-Tak Choi
- Department of Pathology, University of California at San Francisco, San Francisco, California.
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19
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DelSignore M, Jeong T, Denmark G, Feldman D, Shih A, Zukerberg L, Chung DC. Incidence and natural history of gastric high-grade dysplasia in patients with familial adenomatous polyposis syndrome. Gastrointest Endosc 2023; 97:25-34.e6. [PMID: 36113625 DOI: 10.1016/j.gie.2022.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/24/2022] [Accepted: 09/03/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Familial adenomatous polyposis (FAP) is characterized by high risks of colonic and extracolonic tumors. Recent studies have suggested a rising risk for gastric cancer (GC). We sought to define the spectrum of premalignant gastric polyps in FAP, focusing on high-grade dysplasia (HGD). METHODS The gastric phenotypes of 118 patients diagnosed with FAP or attenuated FAP in our Hereditary Gastrointestinal Cancer Registry were retrospectively reviewed. To analyze the clinical features associated with the diagnosis of HGD, we established an age- and sex-matched control group of FAP patients from our cohort without gastric HGD in a 4:1 ratio. RESULTS The spectrum and frequency of gastric polyps in individuals with FAP included fundic gland polyps (67.9%), hyperplastic polyps/foveolar hyperplasia (19.6%), tubular adenomas (15.2%), foveolar adenomas (10.7%), and pyloric gland adenomas (6.3%). Ten patients (8.9%) exhibited gastric HGD at a mean age of 55 ± 13 years, and HGD was seen in all polyp types. When compared with control subjects, HGD was associated with a high diversity of gastric polyp histology, prior low-grade dysplasia, severe gastric polyposis, and prior Whipple surgery (P = 2.0E-5, .003, .024, and .04, respectively). Two patients (1.7%) with HGD were diagnosed with GC. However, the remaining 8 patients with HGD have been under surveillance for an average of 5.8 ± 4.5 years without progression to GC. CONCLUSIONS Gastric HGD in FAP may be more common than previously appreciated. The natural history of HGD is variable, and most patients with HGD do not appear to progress to GC.
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Affiliation(s)
- Marisa DelSignore
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Tiffany Jeong
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Grant Denmark
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Dan Feldman
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Angela Shih
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Lawrence Zukerberg
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel C Chung
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Center for Cancer Risk Assessment, Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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20
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The Approach to Performance of Quality Upper Endoscopy in Lynch Syndrome (QUELS): An International Expert Statement. J Clin Gastroenterol 2023; 57:31-38. [PMID: 36504228 DOI: 10.1097/mcg.0000000000001799] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limited. Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage UGI cancers. On the basis of the emerging favorable evidence derived from EGD surveillance programs, the 2022 National Comprehensive Cancer Network (NCCN) Guidelines for LS recommend UGI surveillance with EGD starting between age 30 and 40 years with repeat EGDs every 2 to 4 years, preferably in conjunction with colonoscopy, in all patients with a germline pathogenic variant (PV) in MLH1, MSH2, EPCAM, and MSH6 and, because of the lack of data, consideration in PMS2. Standardization of the approach to performing EGD surveillance in LS and reporting clinically actionable findings is requisite for both improving quality and understanding the cost efficiency and outcomes of patients undergoing EGD as a surveillance tool. Accordingly, the primary objective of this Quality of Upper Endoscopy in Lynch Syndrome (QUELS) statement is to articulate a framework for standardizing the approach to performing and reporting EGD findings in patients with LS by introducing emerging quality metrics. The recommendations presented herein were developed from available evidence and consensus-based expert opinion and provide a practical approach for clinicians applying EGD surveillance in accordance with the most recent and existing LS guidelines.
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21
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Jelsig AM, Qvist N, Bertelsen B, Christensen LL, Grossjohan H, Lautrup CK, Sunde L, Tørring PM, Ljungman K, Christensen LT, Karstensen JG. Distinct gastric phenotype in patients with pathogenic variants in SMAD4: A nationwide cross-sectional study. Endosc Int Open 2022; 10:E1537-E1543. [PMID: 36531685 PMCID: PMC9754866 DOI: 10.1055/a-1954-0522] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 09/30/2022] [Indexed: 10/14/2022] Open
Abstract
Background and study aims In most patients with juvenile polyposis Syndrome, it is possible to detect a pathogenic germline variant in SMAD4 or BMPR1A . It is well known that patients with a pathogenic variant in SMAD4 have a higher risk of gastric polyposis and gastric cancer compared to BMPR1A carriers, but the natural history of gastric involvement is poorly described. We aimed to systematically review endoscopic and histopathological gastric findings in Danish patients with pathogenic variants in SMAD4. Patients and methods This was a retrospective, cross-sectional study including endoscopic and histological gastric findings in all known Danish patients with pathogenic variants in SMAD4 . The patients were identified by data from various registries as well as from clinical genetic departments and laboratories. Results We identified 41 patients (2-72 years) with a pathogenic SMAD4 variant . In 31 patients, we were able to retrieve information on upper gastrointestinal endoscopy. Eighty-seven percent had at least one gastric abnormality including erythema (72 %) and edema (72 %). Half of the patients also had vulnerability of the mucosa and 68 % had gastric polyposis. An increasing frequency of abnormalities were observed with increasing age. Gastric cancer was diagnosed in 5 % of the cases and 22 % had a gastrectomy mainly because of massive polyposis. Conclusions This study showed that most patients with pathogenic SMAD4 variants have a distinct phenotype of the gastric mucosa, and with an increasing severity in the elderly patients. These findings provide new insights into the natural history of gastric manifestations in patients with pathogenic SMAD4 variants.
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Affiliation(s)
- Anne Marie Jelsig
- Department of Clinical Genetics, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | - Niels Qvist
- Research Unit for Surgery, Odense University Hospital, Odense Denmark; University of Southern Denmark, Odense, Denmark
| | - Birgitte Bertelsen
- Department of Genomic Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark
| | | | - Hanne Grossjohan
- Department of Gastrointestinal Surgery, University Hospital of Copenhagen, Rigshospitalet, Denmark
| | | | - Lone Sunde
- Department of Clinical Genetics, Aalborg University Hospital, Denmark
| | | | - Ken Ljungman
- Department of Surgery, Aarhus University Hospital, Arhus, Denmark
| | | | - John Gásdal Karstensen
- Danish Polyposis Registry, Gastrounit, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark,Department of Clinical Medicine, University of Copenhagen, Denmark
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22
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Endoscopic Surveillance and Treatment of Upper GI Tract Lesions in Patients with Familial Adenomatous Polyposis-A New Perspective on an Old Disease. Genes (Basel) 2022; 13:genes13122329. [PMID: 36553595 PMCID: PMC9777896 DOI: 10.3390/genes13122329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Patients with FAP develop up to thousands of colorectal adenomas as well as lesions in the upper GI tract. In FAP, the upper digestive lesions include gastric fundic gland polyps (FGPs), antrum adenomas, duodenal or small intestinal adenomas, and carcinoma. Patients, after colectomy, are still at significant risk for extracolonic malignancies. Advances in endoscope resolution and optical enhancement technologies allow endoscopists to provide assessments of benign and malignant polyps. For this reason, in the past decades, endoscopic resection techniques have become the first line of treatment in patients with polyps in the upper GI, whereby polyps and even early cancers can be successfully cured. In FAP patients, endoscopic ampullectomy appears to be a safe and effective way of treating patients with ampullary tumors. According to current indications, endoscopic retrograde cholangiopancreatography (ERCP) and stenting of the main pancreatic duct follow ampullectomy.
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23
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Long JM, Ebrahimzadeh J, Stanich PP, Katona BW. Endoscopic Surveillance in Patients with the Highest Risk of Gastric Cancer: Challenges and Solutions. Cancer Manag Res 2022; 14:2953-2969. [PMID: 36238953 PMCID: PMC9553156 DOI: 10.2147/cmar.s277898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 09/22/2022] [Indexed: 11/23/2022] Open
Abstract
Gastric cancer is one of the most significant causes of cancer-related morbidity and mortality worldwide. Recognized modifiable risk factors include Helicobacter pylori infection, geographic location, select dietary factors, tobacco use and alcohol consumption. In addition, multiple hereditary cancer predisposition syndromes are associated with significantly elevated gastric cancer risk. Endoscopic surveillance in hereditary gastric cancer predisposition syndromes has the potential to identify gastric cancer at earlier and more treatable stages, as well as to prevent development of gastric cancer through identification of precancerous lesions. However, much uncertainty remains regarding use of endoscopic surveillance in hereditary gastric cancer predisposition syndromes, including whether or not it should be routinely performed, the surveillance interval and age of initiation, cost-effectiveness, and whether surveillance ultimately improves survival from gastric cancer for these high-risk individuals. In this review, we outline the hereditary gastric cancer predisposition syndromes associated with the highest gastric cancer risks. Additionally, we cover current evidence and guidelines addressing hereditary gastric cancer risk and surveillance in these syndromes, along with current challenges and limitations that emphasize a need for continued research in this field.
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Affiliation(s)
- Jessica M Long
- Division of Hematology and Oncology, Penn Medicine, Philadelphia, PA, USA
| | | | - Peter P Stanich
- Division of Gastroenterology, Hepatology & Nutrition, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA,Correspondence: Bryson W Katona, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, 751 South Pavilion, Philadelphia, PA, 19104, USA, Tel +1-215-349-8222, Fax +1-215-349-5915, Email
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Sato C, Takahashi K, Sato H, Naruse T, Nakajima N, Takatsuna M, Mizuno KI, Hashimoto S, Takeuchi M, Yokoyama J, Kobayashi M, Terai S. Endoscopic Findings and Treatment of Gastric Neoplasms in Familial Adenomatous Polyposis. J Gastric Cancer 2022; 22:381-394. [PMID: 36316112 PMCID: PMC9633932 DOI: 10.5230/jgc.2022.22.e30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 08/09/2022] [Accepted: 08/23/2022] [Indexed: 08/30/2023] Open
Abstract
PURPOSE Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP. MATERIALS AND METHODS A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes. RESULTS Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs. Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014). CONCLUSIONS Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.
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Affiliation(s)
- Chihiro Sato
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kazuya Takahashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
| | - Hiroki Sato
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takumi Naruse
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Nao Nakajima
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masafumi Takatsuna
- Department of Gastroenterology, Nagaoka Red Cross Hospital, Niigata, Japan
| | - Ken-Ichi Mizuno
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Satoru Hashimoto
- Department of Gastroenterology, Saiseikai Kawaguchi General Hospital, Saitama, Japan
| | - Manabu Takeuchi
- Department of Gastroenterology, Nagaoka Red Cross Hospital, Niigata, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Masaaki Kobayashi
- Department of Gastroenterology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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25
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Mankaney GN, Cruise M, Sarvepalli S, Bhatt A, Liska D, Burke CA. Identifying factors associated with detection of sessile gastric polyps in patients with familial adenomatous polyposis. Endosc Int Open 2022; 10:E1080-E1087. [PMID: 35979026 PMCID: PMC9377824 DOI: 10.1055/a-1839-5185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 04/25/2022] [Indexed: 11/20/2022] Open
Abstract
Background and study aims Gastric cancer (GC) is increasingly reported and a leading cause of death in patients with familial adenomatous polyposis (FAP). Identifying features in patients with FAP who harbor sessile gastric polyps, likely precursors to GC, may lead to alterations in endoscopic surveillance in those patients and allow endoscopic intervention to decrease the risk of GC. The aim of this study was to identify demographic and clinical factors in patients with FAP who harbor sessile gastric polyps. Patients and methods We retrospectively compared demographic, clinical, and endoscopic features in consecutive adult patients with FAP who presented for a surveillance endoscopy at a tertiary-care center with a FAP registry who harbor sessile gastric polyps to those without them. Sessile gastric polyps included pyloric gland adenomas, gastric adenomas, hyperplastic polyps, and fundic gland polyps with high-grade dysplasia. We also display the location of germline APC pathogenic variants in patients with and without sessile gastric polyps. Results Eighty patients with FAP were included. Their average age was 48 years and 70 % were male . Nineteen (24 %) had sessile gastric polyps. They were older ( P < 0.03), more likely to have a family history of GC ( P < 0.05), white mucosal patches in the proximal stomach ( P < 0.001), and antral polyps ( P < 0.026) compared to patients without a gastric neoplasm. No difference in Spigelman stage, extra-intestinal manifestations, or surgical history was note. 89 % of patients with a gastric neoplasm had an APC pathogenic variant 5' to codon 1309. Conclusions Specific demographic, endoscopic, and genotypic features are associated with patients with FAP who harbor sessile gastric polyps. We recommend heightened awareness of these factors when performing endoscopic surveillance of the stomach with resection of gastric neoplasia when identified.
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Affiliation(s)
- Gautam N. Mankaney
- Virginia Mason Franciscan Health – Digestive Disease Institute, Seattle, Washington, United States
| | - Michael Cruise
- Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio, United States
| | - Shashank Sarvepalli
- Baylor College of Medicine – Digestive Diseases, Houston, Texas, United States
| | - Amit Bhatt
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, United States
| | - David Liska
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, United States
| | - Carol A. Burke
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, United States
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26
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Novel Endoscopic Polypectomy Surveillance Technique for Fundic Gland Polyps in Familial Adenomatous Polyposis Can Improve Early Detection of Dysplasia and Gastric Cancer. Am J Gastroenterol 2022; 117:1246-1254. [PMID: 35584332 DOI: 10.14309/ajg.0000000000001833] [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] [Received: 09/22/2020] [Accepted: 05/16/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Fundic gland polyps (FGPs) are commonly found in patients with familial adenomatous polyposis (FAP) and are considered benign. Biopsies are not routinely performed, and conventional forceps may be time-consuming and/or yield nonrepresentative histology. The purpose of this study was to evaluate the role of a novel endoscopic polypectomy surveillance (EPS), a large volume cold-snare polypectomy technique of random FGPs, in the incidence of dysplasia and gastric cancer (GC) in FAP. METHODS This is a retrospective longitudinal cohort of patients with FAP referred to a tertiary care center for duodenal adenoma surveillance and who underwent EPS of FGPs between 2001 and 2019. Demographic, endoscopic, and clinicopathologic information was reviewed. RESULTS Thirty-five patients with FAP were identified at initial endoscopy by the mean age of 43.4 years (±12.8). One hundred thirteen surveillance endoscopies were performed in total using EPS. Dysplasia of FGPs was present on initial esophagogastroduodenoscopy in 7 patients (20%), and 13 additional patients (46.4%) progressed to low-grade dysplasia. Three patients (15%) who subsequently had progression to GC were found to have signet ring cell cancer within the foci of FGPs through EPS. One patient presented as metastatic GC. Progression from nondysplastic FGP to low-grade dysplasia occurred over 63 months (±46.3) with further progression to GC over 34 months (±8.5). Endoscopic risk factors for cancer were polyps >10 mm in size ( P < 0.001) and carpeting of polyps ( P < 0.001). The 5-year cumulative incidence of developing dysplasia was 35.7%. DISCUSSION We identified that the incidence of dysplasia and GC is higher than previously reported in patients with FAP. Our study used a novel EPS technique and was able to identify GC within the foci of FGPs. Upper endoscopic guidelines should include a more rigorous sampling method for FGPs, such as EPS, to optimize early detection of dysplasia and GC.
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Takao A, Koizumi K, Takao M, Inokuchi T, Iijima T, Kojika E, Urushibara M, Horiguchi SI, Yamaguchi T. Upper gastrointestinal tumors are unrelated to the APC genotype in APC-associated polyposis. Jpn J Clin Oncol 2022; 52:554-561. [PMID: 35296888 DOI: 10.1093/jjco/hyac029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 02/22/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND In patients with APC-associated polyposis, the prevalence of upper gastrointestinal tumors and the relationship between these and Helicobacter pylori infection have not been clarified in detail. The present study aimed to clarify the features of upper gastrointestinal lesions in patients with APC-associated polyposis. METHODS Consecutive patients with APC-associated polyposis who underwent esophagogastroduodenoscopy between 2004 and 2018 were recruited. RESULTS In total, 36 patients were enrolled. The types of gastrointestinal tumor observed were fundic gland polyposis in 28 patients (77.8%), gastric adenoma in 15 patients (41.7%), duodenal adenoma in 27 patients (75.0%) and periampullary adenoma in 20 patients (55.6%). The phenotype of these upper gastrointestinal tumors was not necessarily the same in patients belonging to the same family. Germline variants in the APC gene were distributed across various sites, regardless of the presence or absence of upper gastrointestinal lesions, and none of the tumors correlated with the genotype or phenotype of upper gastrointestinal tumors. Fundic gland polyposis was observed in 28 of 31 patients without a H. pylori infection and in none of the patients with a H. pylori infection (P = 0.00015). After eradication therapy for H. pylori, fundic gland polyposis developed in one, previously infected patient. CONCLUSION The upper gastrointestinal tumor phenotype was not associated with the genotype in patients with APC-associated polyposis. Ascertaining the H. pylori infection status is helpful for endoscopic surveillance of upper gastrointestinal tumors in patients with APC-associated polyposis.
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Affiliation(s)
- Akinari Takao
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Koichi Koizumi
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Misato Takao
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Takuhiko Inokuchi
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Takeru Iijima
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Ekumi Kojika
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Makiko Urushibara
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Shin-Ichiro Horiguchi
- Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
| | - Tatsuro Yamaguchi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital.,Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital
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Kim W, Kidambi T, Lin J, Idos G. Genetic Syndromes Associated with Gastric Cancer. Gastrointest Endosc Clin N Am 2022; 32:147-162. [PMID: 34798983 DOI: 10.1016/j.giec.2021.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although environmental factors such as Helicobacter pylori, tobacco, and diet are major contributors to the development of gastric cancer (GC) worldwide, it is estimated that up to 5% to 10% of GC cases are due to an underlying hereditary susceptibility caused by germline pathogenic variants. Hereditary diffuse gastric cancer (HDGC) caused by germline pathogenic variants in the CDH1 gene is the principal familial GC syndrome. However, other well-established hereditary gastrointestinal syndromes have been associated with an increased risk of GC. In this review, we will discuss the latest insights and advances in our understanding of GC associated with Lynch syndrome (LS), familial adenomatous polyposis (FAP), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Li-Fraumeni syndrome (LFS), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). We will also discuss the emergence of new associations of the homologous recombination pathway genes (BRCA1, BRCA2) with GC.
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Affiliation(s)
- Woojin Kim
- City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA
| | - Trilokesh Kidambi
- City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA
| | - James Lin
- City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA
| | - Gregory Idos
- City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
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29
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Stanich PP, Sullivan B, Kim AC, Kalady MF. Endoscopic Management and Surgical Considerations for Familial Adenomatous Polyposis. Gastrointest Endosc Clin N Am 2022; 32:113-130. [PMID: 34798980 DOI: 10.1016/j.giec.2021.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Familial adenomatous polyposis (FAP) is the development of many adenomatous colorectal polyps. Colonoscopy is recommended to start at age 10 to 12 years at intervals of 1 to 2 years. Colectomy is clearly indicated for malignancy or significant colorectal symptoms. After colectomy, endoscopic surveillance is still critical. Duodenal and gastric polyposis is also found in almost all patients with FAP. Screening with upper endoscopy and ampullary visualization is recommended, generally determined by age and staging of duodenal polyposis, but guidelines are increasingly factoring in ampullary and gastric manifestations. Surgical management of malignancy or advanced upper tract manifestations is needed.
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Affiliation(s)
- Peter P Stanich
- Division of Gastroenterology, Hepatology & Nutrition, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Suite 200, Columbus, OH 43210, USA.
| | - Brian Sullivan
- Division of Gastroenterology, Duke University Medical Center, 2301 Erwin Road, Durham, NC 27710, USA. https://twitter.com/gi_sullivan
| | - Alex C Kim
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, N924 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210, USA. https://twitter.com/CRS_HIPEC
| | - Matthew F Kalady
- Division of Colorectal Surgery, The Ohio State University Wexner Medical Center, 737 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210, USA. https://twitter.com/MattKaladyMD
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30
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Advances in the Aetiology & Endoscopic Detection and Management of Early Gastric Cancer. Cancers (Basel) 2021; 13:cancers13246242. [PMID: 34944861 PMCID: PMC8699285 DOI: 10.3390/cancers13246242] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/06/2021] [Accepted: 12/10/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Gastric adenocarcinoma has remained a highly lethal disease. Awareness and recognition of preneoplastic conditions (including gastric atrophy and intestinal metaplasia) using high-resolution white-light endoscopy as well as chromoendoscopy is therefore essential. Helicobacter pylori, a class I carcinogen, remains the main contributor to the development of sporadic distal gastric neoplasia. Management of early gastric neoplasia with endoscopic resections should be in line with standard indications. A multidisciplinary approach to any case of an early gastric neoplasia is imperative. Hereditary forms of gastric cancer require a tailored approach and individua-lized surveillance. Abstract The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.
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A tumour-resident Lgr5 + stem-cell-like pool drives the establishment and progression of advanced gastric cancers. Nat Cell Biol 2021; 23:1299-1313. [PMID: 34857912 DOI: 10.1038/s41556-021-00793-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 10/12/2021] [Indexed: 12/31/2022]
Abstract
Gastric cancer is among the most prevalent and deadliest of cancers globally. To derive mechanistic insight into the pathways governing this disease, we generated a Claudin18-IRES-CreERT2 allele to selectively drive conditional dysregulation of the Wnt, Receptor Tyrosine Kinase and Trp53 pathways within the gastric epithelium. This resulted in highly reproducible metastatic, chromosomal-instable-type gastric cancer. In parallel, we developed orthotopic cancer organoid transplantation models to evaluate tumour-resident Lgr5+ populations as functional cancer stem cells via in vivo ablation. We show that Cldn18 tumours accurately recapitulate advanced human gastric cancer in terms of disease morphology, aberrant gene expression, molecular markers and sites of distant metastases. Importantly, we establish that tumour-resident Lgr5+ stem-like cells are critical to the initiation and maintenance of tumour burden and are obligatory for the establishment of metastases. These models will be invaluable for deriving clinically relevant mechanistic insights into cancer progression and as preclinical models for evaluating therapeutic targets.
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32
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Mankaney G, Cruise M, Burke CA. Finding the needle in a haystack: approach to detection of high-risk gastric lesions in familial adenomatous polyposis. Gastrointest Endosc 2021; 94:1043-1045. [PMID: 34598775 DOI: 10.1016/j.gie.2021.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 08/14/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Gautam Mankaney
- Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, Seattle, Washington
| | - Michael Cruise
- Pathology and Laboratory Medicine Institute, Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Colorectal Surgery, Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
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33
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Gastric neoplasms in patients with familial adenomatous polyposis: endoscopic and clinicopathologic features. Gastrointest Endosc 2021; 94:1030-1042.e2. [PMID: 34146551 DOI: 10.1016/j.gie.2021.06.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 06/05/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups. METHODS Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined. RESULTS Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features. CONCLUSIONS Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.
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Bhandari P, Sapra A, Lopp L, Albers CE, Hutchings S. Constipation Misperception: Could It Be Familial Adenomatosis Polyposis? Cureus 2021; 13:e18656. [PMID: 34790442 PMCID: PMC8583244 DOI: 10.7759/cureus.18656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2021] [Indexed: 12/04/2022] Open
Abstract
Colorectal cancer is the second leading cause of cancer deaths in the United States. Familial adenomatosis polyposis (FAP) is a rare cause of colorectal cancer. The United States Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years. While age is the most important risk factor, we need to consider the family history of colorectal cancer. FAP is a rare cause of colorectal cancer, leading to high morbidity and mortality if undetected and undiagnosed. It is easy to overlook the family history in a busy primary care clinic with limited patient encounter times. Clinicians mustn't forget this important piece of information as it can give leads for further patient evaluation. We present a case report of a 21-year-old male who presented to our clinic to establish primary care and with vague abdominal complaints. Still, the concerning family history of early onset colon cancer in his half-sister raised red flags and directed us to further evaluate. Further evaluation revealed our patient, in fact, had FAP.
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Affiliation(s)
- Priyanka Bhandari
- Family and Community Medicine, Southern Illinois University School of Medicine, Springfield, USA
| | - Amit Sapra
- Family and Community Medicine, Southern Illinois University School of Medicine, Springfield, USA
| | - Lauri Lopp
- Family and Community Medicine, Southern Illinois University School of Medicine, Springfield, USA
| | - Christine E Albers
- Family and Community Medicine, Southern Illinois University School of Medicine, Springfield, USA
| | - Sarah Hutchings
- Family and Community Medicine, Southern Illinois University School of Medicine, Springfield, USA
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Orr CE, Beneck D, Jessurun J, Qin L, Tyryshkin K, Yantiss RK, Chen YT. High interobserver variability and frequent overdiagnosis of dysplasia in fundic gland polyps can be improved by detecting atypia on the surface epithelium and an abrupt transition to non-neoplastic cells. Histopathology 2021; 80:314-321. [PMID: 34424570 DOI: 10.1111/his.14549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 08/16/2021] [Accepted: 08/20/2021] [Indexed: 11/29/2022]
Abstract
AIMS Fundic gland polyps (FGPs) arise sporadically and in combination with familial adenomatous polyposis (FAP). Criteria for distinguishing low-grade dysplasia (LGD) from regenerative atypia in FGPs are not well established. The aims of study were to determine: (i) interobserver variability in diagnosing LGD in FGPs; (ii) bias in diagnosing LGD in FAP patients; and (iii) stringent criteria for LGD in FGPs. METHODS AND RESULTS Five senior pathologists who were blinded to the clinical history reviewed 72 FAP-associated FGPs and 34 sporadic FGPs. Cases were classified as negative (score = 0) or positive (score = 1) for LGD. Each case was assigned a 'combined dysplasia score' (CDS) ranging from 0 to 5 to reflect all five opinions. Fleiss' kappa showed only moderate interobserver agreement (κ = 0.46). Forty-one FGPs were classified as negative for dysplasia by consensus (CDS = 0-1), including 10 (24%) originally diagnosed as LGD. In contrast, all 37 cases classified as LGD by consensus (CDS = 4-5) were originally diagnosed as LGD, indicating that overdiagnosis of dysplasia is more common than underdiagnosis (P = 0.0012). Cytological atypia in the surface epithelium and an abrupt transition between atypical and normal-appearing epithelium were the most sensitive (97% and 100%, respectively) and specific (100% and 98%, respectively) features of dysplasia (P < 0.0001 for both comparisons). Very good agreement was achieved when a diagnosis of dysplasia was based on the presence of both features (κ = 0.85). CONCLUSIONS There is high interobserver variability and a tendency to overdiagnose LGD in FGPs. Strict criteria requiring both surface atypia and abrupt transition for LGD in FGPs result in low interobserver variability.
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Affiliation(s)
- Christine E Orr
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Debra Beneck
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Jose Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Lihui Qin
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Kathrin Tyryshkin
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Yao-Tseng Chen
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
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Martin I, Roos VH, Anele C, Walton SJ, Cuthill V, Suzuki N, Bastiaansen BA, Clark SK, von Roon A, Dekker E, Latchford A. Gastric adenomas and their management in familial adenomatous polyposis. Endoscopy 2021; 53:795-801. [PMID: 32942317 PMCID: PMC8315898 DOI: 10.1055/a-1265-2716] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric adenomas. There is limited understanding of their clinical course and no consensus on management. We reviewed the management of gastric adenomas in patients with FAP from two centers. METHODS Patients with FAP and histologically confirmed gastric adenomas were identified between 1997 and 2018. Patient demographics, adenoma characteristics, and management/surveillance outcomes were collected. RESULTS Of 726 patients with FAP, 104 (14 %; 49 female) were diagnosed with gastric adenomas at a median age of 47 years (range 19 - 80). The median size of gastric adenomas was 6 mm (range 1.5 - 50); 64 (62 %) patients had adenomas located distally to the incisura. Five patients (5 %) had gastric adenomas demonstrating high-grade dysplasia (HGD) on initial diagnosis, distributed equally within the stomach. The risk of HGD was associated with adenoma size (P = 0.04). Of adenomas > 20 mm, 33 % contained HGD. Two patients had gastric cancer at initial gastric adenoma diagnosis. A total of 63 patients (61 %) underwent endoscopic therapy for gastric adenomas. Complications occurred in three patients (5 %) and two (3 %) had recurrence, all following piecemeal resection of large (30 - 50 mm) lesions. Three patients were diagnosed with gastric cancer at median follow-up of 66 months (range 66 - 115) after initial diagnosis. CONCLUSIONS We observed gastric adenomas in 14 % of patients with FAP. Of these, 5 % contained HGD; risk of HGD correlated with adenoma size. Endoscopic resection was feasible, with few complications and low recurrence rates, but did not completely eliminate the cancer risk.
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Affiliation(s)
- Isabel Martin
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom,Department of Surgery and Cancer, Imperial College London, United Kingdom
| | - Victorine H. Roos
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Netherlands
| | - Chukwuemeka Anele
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom,Department of Surgery and Cancer, Imperial College London, United Kingdom
| | - Sarah-Jane Walton
- Department of Surgery, Basildon and Thurrock University Hospital, Basildon, United Kingdom
| | - Victoria Cuthill
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom
| | - Noriko Suzuki
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom
| | - Barbara A. Bastiaansen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Netherlands
| | - Susan K. Clark
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom,Department of Surgery and Cancer, Imperial College London, United Kingdom
| | - Alexander von Roon
- Department of Surgery, University College Hospital, London, United Kingdom
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Netherlands
| | - Andrew Latchford
- The Polyposis Registry, St. Mark’s Hospital, London, United Kingdom,Department of Surgery and Cancer, Imperial College London, United Kingdom
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Sano W, Inoue F, Hirata D, Iwatate M, Hattori S, Fujita M, Sano Y. Sporadic fundic gland polyps with dysplasia or carcinoma: Clinical and endoscopic characteristics. World J Gastrointest Oncol 2021. [DOI: 10.4251/wjgo.v13.i7.487] [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: 02/06/2023] Open
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Sano W, Inoue F, Hirata D, Iwatate M, Hattori S, Fujita M, Sano Y. Sporadic fundic gland polyps with dysplasia or carcinoma: Clinical and endoscopic characteristics. World J Gastrointest Oncol 2021; 13:662-672. [PMID: 34322195 PMCID: PMC8299935 DOI: 10.4251/wjgo.v13.i7.662] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/25/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Fundic gland polyps (FGPs) are the most common gastric polyps and have been regarded as benign lesions with little malignant potential, except in the setting of familial adenomatous polyposis. However, in recent years, the prevalence of FGPs has been increasing along with the widespread and frequent use of proton pump inhibitors (PPIs). To date, several cases of FGPs with dysplasia or carcinoma (FGPD/CAs) have been reported. In this review, we evaluated the clinical and endoscopic characteristics of sporadic FGPD/CAs. Majority of the patients with sporadic FGPD/CAs were middle-aged women receiving PPI therapy and without Helicobacter pylori (H. pylori) infection. Majority of the sporadic FGPD/ CAs occurred in the body of the stomach and were sessile and small with a mean size of 5.4 mm. The sporadic FGPs with carcinoma showed redness, irregular surface structure, depression, or erosion during white light observation and irregular microvessels on the lesion surface during magnifying narrow-band imaging. In addition, sporadic FGPs, even with dysplasia, are likely to progress to cancer slowly. Therefore, frequent endoscopy is not required for patients with sporadic FGPs. However, histopathological evaluation is necessary if endoscopic findings different from ordinary FGPs are observed, regardless of their size. In the future, the prevalence of FGPs is expected to further increase along with the widespread and frequent use of PPIs and decreasing infection rate of H. pylori. Currently, it is unclear whether FGPD/CAs will also increase in the same way as FGPs. However, the trends of these lesions warrant further attention in the future.
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Affiliation(s)
- Wataru Sano
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Fumihiro Inoue
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Daizen Hirata
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Mineo Iwatate
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Santa Hattori
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Mikio Fujita
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
| | - Yasushi Sano
- Gastrointestinal Center, Sano Hospital, Kobe 655-0031, Hyogo, Japan
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Abstract
Approximately 10% of patients with gastric cancer show familial aggregation and up to 3% are related to an inherited cancer syndrome. There are multiple germline pathogenic variants and cancer syndromes associated with an increased risk of gastric cancer. Appropriate assessment of familial and genetic risk may allow a personalized approach to gastric cancer prevention through screening and risk-reducing surgeries. The ability to better identify carriers with pathogenic genetic variants associated with gastric cancer before a diagnosis of cancer requires effective genetic risk assessment and testing, followed by optimal screening and surveillance recommendations to further reduce the morbidity and mortality.
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40
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Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2020 for the Clinical Practice of Hereditary Colorectal Cancer. Int J Clin Oncol 2021; 26:1353-1419. [PMID: 34185173 PMCID: PMC8286959 DOI: 10.1007/s10147-021-01881-4] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/10/2021] [Indexed: 12/14/2022]
Abstract
Hereditary colorectal cancer (HCRC) accounts for < 5% of all colorectal cancer cases. Some of the unique characteristics commonly encountered in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics necessitate different management approaches, including diagnosis, treatment or surveillance, from sporadic colorectal cancer management. There are two representative HCRC, named familial adenomatous polyposis and Lynch syndrome. Other than these two HCRC syndromes, related disorders have also been reported. Several guidelines for hereditary disorders have already been published worldwide. In Japan, the first guideline for HCRC was prepared by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), published in 2012 and revised in 2016. This revised version of the guideline was immediately translated into English and published in 2017. Since then, several new findings and novel disease concepts related to HCRC have been discovered. The currently diagnosed HCRC rate in daily clinical practice is relatively low; however, this is predicted to increase in the era of cancer genomic medicine, with the advancement of cancer multi-gene panel testing or whole genome testing, among others. Under these circumstances, the JSCCR guidelines 2020 for HCRC were prepared by consensus among members of the JSCCR HCRC Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR guidelines 2020 for HCRC.
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Takao M, Yamaguchi T, Eguchi H, Yamada T, Okazaki Y, Tomita N, Nomizu T, Momma T, Takayama T, Tanakaya K, Akagi K, Ishida H. APC germline variant analysis in the adenomatous polyposis phenotype in Japanese patients. Int J Clin Oncol 2021; 26:1661-1670. [PMID: 34106356 DOI: 10.1007/s10147-021-01946-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/25/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Familial adenomatous polyposis (FAP), an autosomal dominant disorder characterized by multiple colonic polyps, is caused by a germline pathogenic variant of the APC gene. However, this variant is not detected in up to 30% of patients with the adenomatous polyposis phenotype. METHODS We performed next-generation sequencing (NGS) to identify the causative genes in FAP patients with 10 or more polyps. For patients in whom the APC germline variant was not able to be identified, we screened for APC mosaicism using high-coverage NGS of APC with DNA from leucocytes and/or frozen tissue. RESULTS The pathogenic APC germline variant was found in 93.3%, 71.6%, and 17.1% of patients with profuse-type polyposis, sparse-type polyposis, and oligo-polyposis, respectively. The APC germline variant detection rate in patients with FAP-related diseases was 69.7% for fundic gland polyposis, 79.7% for duodenal adenoma, 94.7% for desmoid tumor, and 71.4% for thyroid cancer, with increasing numbers of extracolonic lesions associated with an increasing APC germline variant detection rate. A mosaic test detected nine patients with APC mosaicism. A comparison of APC-associated polyposis with APC mosaicism showed that patients with APC mosaicism had a low frequency of duodenal adenoma and a family history of colonic polyposis. CONCLUSIONS We determined the detection rate of the APC germline variant by phenotype and identified APC mosaicism. Genetic testing of FAP patients is important because it can help with surgical decision-making, monitoring, and genetic counseling. Furthermore, genetic testing by NGS proved to be an effective method of detecting APC germline variants.
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Affiliation(s)
- Misato Takao
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.,Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Tatsuro Yamaguchi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. .,Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan. .,Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
| | - Hidetaka Eguchi
- Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Yasushi Okazaki
- Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Naohiro Tomita
- Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tadashi Nomizu
- Department of Surgery, Hoshi General Hospital, Koriyama, Japan
| | - Tomoyuki Momma
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Kohji Tanakaya
- Department of Surgery, Iwakuni Clinical Center, Iwakuni, Japan
| | - Kiwamu Akagi
- Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan
| | - Hideyuki Ishida
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
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Kim K, Clauditz TS, Lee JH, Lauwers GY. Polyps of the Stomach. GASTROINTESTINAL PATHOLOGY 2021:99-123. [DOI: 10.1002/9781119073048.ch5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Noh JH, Song EM, Ahn JY, Yang DH, Lee W, Hong J, Kim A, Na HK, Lee JH, Jung KW, Kim DH, Choi KD, Song HJ, Lee GH, Jung HY. Prevalence and endoscopic treatment outcomes of upper gastrointestinal neoplasms in familial adenomatous polyposis. Surg Endosc 2021; 36:1310-1319. [PMID: 33709227 DOI: 10.1007/s00464-021-08406-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although upper gastrointestinal (GI) neoplasms are not rare in patients with familial adenomatous polyposis (FAP), few studies have focused on them and the long-term outcomes of their treatment by endoscopy. Therefore, we aimed to investigate the prevalence and endoscopic treatment outcomes of upper GI neoplasms in patients with FAP. METHODS Among 215 patients diagnosed with FAP between January 1991 and December 2019, 208 who underwent esophagogastroduodenoscopy were eligible. The clinical features and endoscopic treatment outcomes of upper GI neoplasms were retrospectively investigated and analyzed. RESULTS Among the enrolled patients, 113 (54.3%) had one or more upper GI neoplasms: gastric adenoma (n = 34), gastric cancer (n = 7), nonampullary duodenal adenoma (n = 86), and ampullary adenoma (n = 53). Among patients with gastric neoplasms (n = 37), 24 (64.9%) underwent treatment (endoscopic treatment: 22, surgery: 2). No tumor-related mortality occurred during median follow-up of 106 months (interquartile range [IQR] 63-174). Endoscopic treatment was performed in 47 (54.7%) of 86 patients with nonampullary duodenal adenoma and in 32 (60.4%) of 53 patients with ampullary adenoma. No patient underwent surgery for duodenal neoplasms, and no tumor-related mortality occurred during median follow-up of 88 months (IQR 42-145). The proportion of patients with increased Spigelman stage at 2 years after the initial diagnosis or treatment was significantly higher in untreated group than in the group treated for duodenal neoplasms (27.3% vs. 0.0%, p = 0.001). CONCLUSION Endoscopic surveillance in FAP patients is important for the detection and treatment of upper GI neoplasms in early stage. In particular, endoscopic therapy for duodenal neoplasms can reduce the severity of duodenal polyposis.
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Affiliation(s)
- Jin Hee Noh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Mi Song
- Department of Gastroenterology, Ewha Womans University Medical Center, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Woochang Lee
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jinyoung Hong
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Aram Kim
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Lee SY. Helicobacter pylori-negative Gastric Cancer. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2020.0036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
<i>Helicobacter pylori (H. pylori)</i>-negative gastric cancer is diagnosed when gastric malignancies are found in patients in <i>H. pylori</i>-naïve stomachs. There are four types of noncardiac <i>H. pylori</i>-negative gastric cancers. The signet ring cell-type poorly cohesive carcinoma is most common, followed by the chief cell-predominant type gastric adenocarcinoma of the fundic gland. Extremely well-differentiated adenocarcinoma of the corpus and well-differentiated pyloric gland cancers are rare outside Japan because of country-specific differences in diagnostic criteria. In endemic areas of <i>H. pylori</i> infection, strict criteria are required for diagnosing an <i>H. pylori</i>-naïve stomach. Both invasive and noninvasive <i>H. pylori</i> tests should show negative results in a subject without a history of <i>H. pylori</i> infection. Furthermore, the serum pepsinogen (PG) assay and endoscopic findings of the background gastric mucosa are required to discriminate subjects with past infections owing to spontaneous regression or unintended eradication of <i>H. pylori</i>. There should be no gastric corpus atrophy (PG I ≤70 ng/mL and PG I/II ≤3.0). Gastroscopy should reveal a regular arrangement of collecting venules without gastric xanthoma, metaplastic gastritis, or advanced atrophy over the angle. On biopsy, there should be no gastric atrophy, intestinal metaplasia, neutrophils, or <i>H. pylori</i> infiltration, and only a mild degree of mononuclear cell infiltration is permitted. The types and characteristics of noncardiac <i>H. pylori</i>-negative gastric cancers are summarized in this review, along with current diagnostic challenges found in Korea.
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45
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Lam SK, Lau GKK. Idiopathic multitudinous fundic gland polyposis: A new disease and a management dilemma. JGH OPEN 2021; 5:525-527. [PMID: 33860106 PMCID: PMC8035449 DOI: 10.1002/jgh3.12496] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 01/10/2021] [Accepted: 01/13/2021] [Indexed: 11/23/2022]
Abstract
Two patients with idiopathic multitudinous fundic gland polyposis, a hitherto undescribed condition, were reported. They presented incidentally with a multitude of fundic gland polyps, 52 and 147, without a family history of polyposis, and these polyps were not attributable to the chronic use of proton pump inhibitors. All polyps were removed by hot‐biopsy polypectomy, and each was individually subjected to pathological examination, which showed no evidence of dysplasia. When confronted with gastric polyps of clinically undetermined origin, endoscopists would, to exclude dysplasia, usually resect all if they are few and sample some and survey the others periodically if they are numerous. The condition reported presents a management dilemma: Because the number of the polyps is such that they are manageable by total polypectomy, should this be carried out, despite the labor intensiveness involved, to exclude dysplasia, and are the polyps a variant of syndromic polyposis and therefore carry a malignant potential and inform the need for periodic surveillance and to investigate the patient's kindred? The frequency of this condition and whether it is truly not associated with dysplasia require further studies.
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Affiliation(s)
- Shiu Kum Lam
- The Humanity & Health GI & Liver Centre Hong Kong China.,The University of Hong Kong, Hong Kong Hong Kong China
| | - George K K Lau
- The Humanity & Health Medical Centre Hong Kong China.,The Liver Diseases & Transplant Centre The Fifth Medical Centre of Chinese PLA General Hospital Beijing China.,Steering Committee of the Asian Pacific Association for the Study of the Liver Tokyo Japan.,The Asian Pacific Digestive Week Federation Kuala Lumpur Malaysia
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Ochiai Y, Kikuchi D, Ito S, Takazawa Y, Hoteya S. Large Fundic Gland Polyp Associated with Long-Term Proton Pump Inhibitor Administration Mimicking Gastric-Type Neoplasm. Case Rep Gastroenterol 2021; 15:123-130. [PMID: 33708059 PMCID: PMC7923705 DOI: 10.1159/000512399] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 10/16/2020] [Indexed: 12/30/2022] Open
Abstract
A 57-year-old man with a 10-year history of proton pump inhibitor (PPI) use presented with multiple fundic gland polyps (FGPs) including one >20 mm, whitish, semi-pedunculated polyp. Black spots and cobblestone-like mucosa were also observed in the stomach upon endoscopy; therefore, the lesion was considered to result from long-term PPI administration. Endoscopically, we diagnosed this polyp as a neoplastic lesion with gastric phenotype rather than a non-neoplastic lesion. Biopsy revealed an atypical glandular lesion that was indeterminate for neoplasia; therefore, we performed en bloc resection via endoscopic submucosal dissection (ESD) of the 22 × 22 × 10 mm-sized polyp. Histologically, the polyp was composed of hyperplastic foveolar epithelia in the upper half of the mucosa and hyperplastic fundic glands in the lower half of the mucosa, with luminal dilatation and parietal cell protrusion. The pathological diagnosis for this ESD specimen was FGP associated with PPI administration. We herein describe this rare case of a large FGP in Helicobacter pylori-uninfected gastric mucosa associated with long-term PPI administration, which was mimicking gastric-type neoplasm and resected by endoscopy.
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Affiliation(s)
- Yorinari Ochiai
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Shinji Ito
- Department of Pathology, Toranomon Hospital, Tokyo, Japan
| | | | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
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Nonaka S, Hashimoto T, Oda I, Sekine S. Sporadic pyloric gland adenoma associated with a large fundic gland polyp: genetic evidence for stepwise progression. Gastric Cancer 2020; 23:1102-1106. [PMID: 32415517 DOI: 10.1007/s10120-020-01082-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 05/03/2020] [Indexed: 02/07/2023]
Abstract
Pyloric gland adenoma (PGA) is an uncommon variant of gastric adenoma exhibiting pyloric gland/mucous neck cell differentiation. We present a sporadic PGA associated with a large fundic gland polyp (FGP) in a woman in her 40 s without Helicobacter pylori infection. The polyp, measuring 25 mm in size, was located in the middle gastric body and was removed by endoscopic submucosal dissection. Histological examination revealed three morphologically distinct components: FGP, FGP with large cysts, and PGA. A genetic analysis identified a truncating APC mutation in all the three components, supporting their histogenetic relationship. Additionally, a GNAS mutation was detected in two components, FGP with large cysts and PGA, whereas a KRAS mutation was exclusively found in the PGA component. Thus, despite the unusual presentation, the PGA component harbored prototypical genetic alterations. The differential genetic alterations observed in the three components imply that they represent stepwise progression from FGP to PGA.
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Affiliation(s)
- Satoru Nonaka
- Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Taiki Hashimoto
- Division of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shigeki Sekine
- Division of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. .,Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
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Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis. Clin Transl Gastroenterol 2020; 10:e00053. [PMID: 31211760 PMCID: PMC6613862 DOI: 10.14309/ctg.0000000000000053] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Duodenal cancer in familial adenomatous polyposis (FAP) arises from adenomas. Differentially expressed genes (DEGs) in the duodenal adenoma-carcinoma pathway have been identified in murine FAP models, but similar data in patients with FAP are limited. Identifying such changes may have significance in understanding duodenal polyposis therapies and identifying cancer biomarkers. We performed a genome-wide transcriptional analysis to describe the duodenal adenoma-carcinoma sequence and determine changes distinguishing patients with FAP with and without duodenal cancer.
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Surveillance for pathology associated with cancer on endoscopy (SPACE): criteria to identify high-risk gastric polyps in familial adenomatous polyposis. Gastrointest Endosc 2020; 92:755-762. [PMID: 32380015 DOI: 10.1016/j.gie.2020.04.065] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 04/10/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Gastric cancer is an extracolonic manifestation of familial adenomatous polyposis (FAP) and is associated with high-risk gastric polyps. There are no known endoscopic criteria to identify these high-risk polyps. Our aim was to develop endoscopic criteria to identify high-risk polyps on endoscopy in FAP. METHODS We prospectively collected 150 gastric polyps in consecutive patients undergoing surveillance EGD at the Cleveland Clinic. Pictures were taken of each polyp under narrow-band imaging and high-definition white light. In an exploratory phase, 5 endoscopists developed consensus criteria using the images to distinguish high-risk (pyloric gland adenoma, tubular adenoma, hyperplastic) from low-risk (fundic gland with low-grade or no dysplasia) polyps. In the assessment phase, endoscopists were blinded to polyp pathology and used the criteria to predict the individual polyp risk category. To measure diagnostic accuracy, we reported the mean sensitivity, specificity, and interrater agreement (κ). RESULTS Consensus criteria were developed based on 16 low-risk and 9 high-risk polyps. The final 149 polyps consisted of 128 low-risk and 22 high-risk polyps (1 polyp was excluded from analysis). Using the criteria, the 5 endoscopists distinguished high- from low-risk polyps with a mean sensitivity and specificity of 79% (16.3%) and 78.8% (10.8%), respectively. The κ coefficient was .45, indicating moderate agreement. CONCLUSIONS We developed endoscopic criteria to distinguish between high- and low-risk polyps associated with gastric cancer in FAP. The criteria provide guidance to endoscopists in targeting high-risk polyps while surveying the stomach of patients with proximal gastric polyposis.
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Disciglio V, Fasano C, Cariola F, Forte G, Grossi V, Sanese P, Lepore Signorile M, Resta N, Lotesoriere C, Stella A, Lolli I, Simone C. Gastric polyposis and desmoid tumours as a new familial adenomatous polyposis clinical variant associated with APC mutation at the extreme 3'-end. J Med Genet 2020; 57:356-360. [PMID: 31591141 PMCID: PMC7231465 DOI: 10.1136/jmedgenet-2019-106299] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 09/04/2019] [Accepted: 09/07/2019] [Indexed: 01/23/2023]
Abstract
Germline mutations of the APC gene, which encodes a multidomain protein of 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Three FAP clinical variants are correlated with the location of APC mutations: (1) classic FAP with profuse polyposis (>1000 adenomas), associated with mutations from codon 1250 to 1424; (2) attenuated FAP (<100 adenomas), associated with mutations at APC extremities (before codon 157 and after codon 1595); (3) classic FAP with intermediate colonic polyposis (100-1000 adenomas), associated with mutations located in the remaining part of APC In an effort to decipher the clinical phenotype associated with APC C-terminal germline truncating mutations in patients with FAP, after screening APC mutations in one family whose members (n=4) developed gastric polyposis, colon oligo-polyposis and desmoid tumours, we performed a literature meta-analysis of clinically characterised patients (n=97) harbouring truncating mutations in APC C-terminus. The APC distal mutations identified in this study cluster with a phenotype characterised by colon oligo-polyposis, diffuse gastric polyposis and desmoid tumours. In conclusion, we describe a novel FAP clinical variant, which we propose to refer to as Gastric Polyposis and Desmoid FAP, that may require tailored management.
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Affiliation(s)
- Vittoria Disciglio
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Candida Fasano
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Filomena Cariola
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Giovanna Forte
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Valentina Grossi
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Paola Sanese
- Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Bari, Italy
| | - Martina Lepore Signorile
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Nicoletta Resta
- Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Bari, Italy
| | - Claudio Lotesoriere
- Department of Oncology, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Alessandro Stella
- Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Bari, Italy
| | - Ivan Lolli
- Department of Oncology, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Cristiano Simone
- Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
- Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Bari, Italy
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