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Fukuya H, Sasaki T, Ihara E, Yoshimura D, Okitsu R, Ohkubo A, Matsushita Y, Hasuda H, Sakaguchi Y, Harada N. A case of gastric-localized juvenile polyposis syndrome with SMAD4 mosaic variant presenting as a slowly progressive phenotype. Clin J Gastroenterol 2025:10.1007/s12328-025-02146-7. [PMID: 40372668 DOI: 10.1007/s12328-025-02146-7] [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: 01/15/2025] [Accepted: 05/02/2025] [Indexed: 05/16/2025]
Abstract
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder caused by pathogenic variants in the mothers against decapentaplegic homolog 4 (SMAD4) and bone morphogenetic protein receptor type 1A (BMPR1A) genes. It is characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. We report a case of a 73-year-old Japanese male with sporadic, gastric-localized JPS harboring a SMAD4 mosaic variant who presented with slowly progressive endoscopic lesions. Endoscopy at the age of 55 revealed erythematous and edematous mucosa in the gastric fundus. During the following 18 years, the patient developed progressive gastric polyposis, leading to refractory anemia and hypoalbuminemia. Genetic testing identified a SMAD4 frameshift mosaic variant (c.1245_1248del (p.Asp415Glufs)) with an allele frequency of 23%. A total gastrectomy with D1 lymphadenectomy was performed, confirming the JPS diagnosis and the identification of a localized gastric adenocarcinoma without lymph node metastasis. This case highlights the unique natural history of JPS with a SMAD4 mosaic variant, which potentially contributes to a slowly progressive phenotype.
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Affiliation(s)
- Hiroki Fukuya
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan.
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
| | - Taisuke Sasaki
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Daisuke Yoshimura
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Ryota Okitsu
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Akito Ohkubo
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yuki Matsushita
- Department of Pediatrics, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
- Department of Clinical genomics, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Hirofumi Hasuda
- Department of Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yoshihisa Sakaguchi
- Department of Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Naohiko Harada
- Department of Gastroenterology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Fukuoka, 810-8563, Japan
- Institute of Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
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Aoun RJN, Kalady MF. Hereditary Colorectal Cancer: From Diagnosis to Surgical Options. Clin Colon Rectal Surg 2025; 38:179-190. [PMID: 40292001 PMCID: PMC12020645 DOI: 10.1055/s-0044-1787884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Hereditary colorectal cancer (CRC) syndromes account for up to 5% of CRC. Patients have an increased risk of CRC and extracolonic cancers, both of which develop at an early age. The main polyposis syndromes include familial adenomatous polyposis, MYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome. The non-polyposis syndromes include Lynch syndrome and familial colorectal cancer type X. Each of the syndromes have distinct but sometimes overlapping phenotypes. Clinical evaluation and ultimately the underlying germline genetic pathogenic variants define the syndromes. Each syndrome has polyp, CRC, and extracolonic risks and management is based on early and timely surveillance with therapeutic and often extended prophylactic surgery. Surgical intervention strategies are individualized, considering not only the earlier onset of malignancies and heightened risks for metachronous cancers but also the patient's needs and quality of life. This article reviews the different diagnostic approaches to hereditary CRC and highlights subsequent disease-specific management and surgical decision-making strategies.
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Affiliation(s)
- Rami James N. Aoun
- Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Matthew F. Kalady
- Division of Colon and Rectal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
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Borsotti E, Nava FL, Benedicenti F, Cini L, Magarotto A, Ferrari D, Cantù P, Vitellaro M, Rausa E, Cavalcoli F. Hereditary Colorectal Cancer Syndromes: Small Bowel Cancer Risk and Endoscopic Surveillance Strategies. Diagnostics (Basel) 2025; 15:819. [PMID: 40218169 PMCID: PMC11988710 DOI: 10.3390/diagnostics15070819] [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: 02/10/2025] [Revised: 03/05/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (LS), and Peutz-Jeghers syndrome (PJS), are associated with an increased risk of small bowel cancer (SBC). Due to the low incidence and non-specific presentation of SBC, effective surveillance strategies are essential for early detection and management. This review aims to evaluate and compare current endoscopic techniques for small bowel surveillance in these patients. Methods: A comprehensive review was conducted using peer-reviewed studies sourced from PubMed. Various endoscopic modalities, including capsule endoscopy (CE), device-assisted enteroscopy (DAE), and intraoperative enteroscopy (IOE), were assessed for their diagnostic yield, safety, and clinical utility. Surveillance recommendations of the different syndromes were also examined. Results: CE offers high sensitivity but lacks histological sampling capability. DAE, including double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE), enables direct visualization, biopsy, and therapeutic interventions, albeit with greater procedural complexity. In FAP, duodenal surveillance follows the Spigelman classification to stratify cancer risk, while jejunal and ileal polyps remain less studied. LS patients have an increased SBC risk, warranting tailored endoscopic approaches. In PJS, surveillance aims to mitigate intussusception risks and allow early malignancy detection. Conclusions: Optimized surveillance strategies in hereditary colorectal cancer syndromes require a multimodal approach, integrating advanced endoscopic techniques with genetic risk stratification. Centralized care in tertiary centers improves outcomes by ensuring standardized surveillance protocols and enhancing early cancer detection. Artificial intelligence (AI) applied to CE and DAE is shaping promising prospects for the future surveillance of small bowel polyps by enhancing diagnostic accuracy and reducing the duration of the diagnostic process. Further research should investigate AI-assisted imaging and molecular biomarkers to optimize screening strategies.
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Affiliation(s)
- Edoardo Borsotti
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Francesca Laura Nava
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Felice Benedicenti
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Laura Cini
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Andrea Magarotto
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Davide Ferrari
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Paolo Cantù
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
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Huang L, Liu X, Li S, Liu Y, Chen W, Li Y, Peng H, Wang X, Xiong P, Yang Q, Wu S, Che L, Zhao H, Deng Y. Multiplex immunohistochemistry reveals histological features of three different intestinal polyp subtypes in pediatric patients. BMC Pediatr 2025; 25:219. [PMID: 40108597 PMCID: PMC11921745 DOI: 10.1186/s12887-024-05376-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/27/2024] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Histologically, our understanding of intestinal polyps remains limited in scope, particularly regarding the diverse subtypes observed in pediatric patients. To enhance our comprehension, three different polyp subtypes including solitary juvenile polyps (SJPs), juvenile polyposis syndrome (JPS)-related polyps, and Peutz‒Jeghers syndrome (PJS)-related polyps were investigated. METHODS This study used advanced multiplex immunohistochemistry (mIHC) technology to analyze polyps comprising 4 SJP, 4 JPS and 4 PJS polyps from 12 individual patients who underwent colonoscopies or radical surgical procedures. subtypes. RESULTS These mIHC analyses revealed some differences among these polyp subtypes. PJS-related polyps, specifically, displayed epithelial dysplasia with dendritic gland hyperplasia and distinct villous structures adorned with finger-like projections on their surfaces. In contrast, SJP and JPS polyps exhibited cystic glandular dilation, with their surfaces lined with continuous but eroded epithelia. Furthermore, PJS polyps had an abundance of microvessels and thick smooth muscle fibers, whereas SJP and JPS polyps were characterized by lymphoid follicle-like structures. CONCLUSIONS These findings not only deepen our structural understanding of various intestinal polyp subtypes but also offer valuable insights that may inform the diagnosis of patients with these conditions.
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Affiliation(s)
- Lanlan Huang
- The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, 410007, China
| | - Xinjia Liu
- The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, 410007, China
| | - Songyang Li
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Yongjie Liu
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Weijian Chen
- Department of Pathology, Hunan Children's Hospital, Changsha, 410000, China
| | - Yana Li
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Hongyan Peng
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Xiangyu Wang
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Peiwen Xiong
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Qinglan Yang
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Shuting Wu
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China
| | - Ling Che
- Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100853, China.
| | - Hongmei Zhao
- Department of Digestive Nutrition, Hunan Children's Hospital, Changsha, 410000, China.
| | - Yafei Deng
- The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, 410007, China.
- The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, Changsha, 410007, China.
- Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, 410007, China.
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Yang M, Tong Z, Yuan Z, Jiang B, Zhao Y, Xu D, Yuan Y. A Novel Missense Variant of BMPR1A in Juvenile Polyposis Syndrome: Assessment of Structural and Functional Alternations. Hum Mutat 2025; 2025:7317429. [PMID: 40226309 PMCID: PMC11919155 DOI: 10.1155/humu/7317429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 01/27/2025] [Indexed: 04/15/2025]
Abstract
Juvenile polyposis syndrome (JPS) is a rare precancerous condition associated with a high susceptibility to colorectal cancer. The genetic basis of JPS has been reported to lie in germline mutations in BMPR1A or SMAD4, resulting in diverse clinical manifestations and an elusive underlying mechanism. We firstly utilized a 139-gene next-generation sequencing (NGS) panel to detect the germline variants and further employed various prediction tools to assess the pathogenicity and functional alternations. Consequently, we identified a novel pathogenic BMPR1A missense variant (c.355C>T; p.R119C). More importantly, we proposed for the first time that the missense variant would lead to a decrease in molecular weight, potentially associated with reduced protein stability, diminished posttranslational modifications, and aberrant alternative splicing. These findings may provide novel perspectives for further exploration into the role of BMPR1A in JPS development. Also, we hope to encourage clinicians to underscore the importance of genetic testing and analysis in facilitating the diagnosis and treatment of diseases.
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Affiliation(s)
- Mengyuan Yang
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Ziyan Tong
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhijun Yuan
- Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Bingjing Jiang
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Yingxin Zhao
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Dong Xu
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Ying Yuan
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China
- Cancer Center of Zhejiang University, Hangzhou, Zhejiang, China
- Binjiang Institute of Zhejiang University, Hangzhou, Zhejiang, China
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Matsubara Y, Nakamura Y, Nakayama Y, Yano T, Ishikawa H, Kumagai H, Umeno J, Uchida K, Jimbo K, Yamamoto T, Ishida H, Suzuki O, Okamoto K, Kakuta F, Koike Y, Kawasaki Y, Sakamoto H. Prevalence and Incidence of Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome in Japan: A Nationwide Epidemiological Survey in 2022. J Gastroenterol Hepatol 2025; 40:473-481. [PMID: 39623880 DOI: 10.1111/jgh.16839] [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: 06/27/2024] [Revised: 10/17/2024] [Accepted: 11/17/2024] [Indexed: 02/11/2025]
Abstract
BACKGROUND AND AIM Peutz-Jeghers syndrome (PJS) and juvenile polyposis syndrome (JPS) are autosomal dominant diseases associated with high cancer risk. In Japan, knowledge about the prevalence and incidence of PJS and JPS is lacking despite being crucial for providing appropriate medical support. We aimed to determine the prevalence and incidence of these diseases. METHODS In 2022, a nationwide questionnaire survey was conducted to determine the number of patients with PJS or JPS by sex and the number of newly confirmed cases from 2019 to 2021. The target facilities included gastroenterology, pediatrics, and pediatric surgery departments, which were stratified into seven classes on the basis of the total number of beds. We randomly selected target facilities using different extraction rates in each class, resulting in 1748/2912 facilities (extraction rate: 60%) as the final sample. We calculated the estimated number of patients using the response and extraction rates. RESULTS A total of 1077 facilities responded to the survey. The estimated numbers of patients with PJS and JPS were 701 (95% confidence interval [CI]: 581-820) and 188 (95% CI: 147-230), respectively. The 3-year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively. Male patients constituted 53.5% and 59.6% in the PJS and JPS groups, respectively. CONCLUSIONS We determined the prevalence and incidence of PJS and JPS in Japan for the first time. Further research is needed to obtain more detailed information, including the clinical differences and outcomes in Japan.
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Affiliation(s)
- Yuri Matsubara
- Department of Public Health, Dokkyo Medical University School of Medicine, Tochigi, Japan
| | | | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan
| | - Tomonori Yano
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideki Kumagai
- Department of Pediatrics, Jichi Medical University, Tochigi, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keiichi Uchida
- Department of Pediatric Surgery, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Keisuke Jimbo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Toshiki Yamamoto
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hideyuki Ishida
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
| | - Okihide Suzuki
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Fumihiko Kakuta
- Department of General Pediatrics, Miyagi Children's Hospital, Sendai, Japan
| | - Yuhki Koike
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yuko Kawasaki
- College of Nursing Art and Science, University of Hyogo, Akashi, Japan
| | - Hirotsugu Sakamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
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Muller M, Baldysiak E, Benech N, Pioche M, Hervieu V, Calavas L, Tusseau M, Dupuis-Girod S, Saurin JC. Deciphering the clinical spectrum of gastric disease in patients with juvenile polyposis syndrome. Gastrointest Endosc 2024; 100:867-877. [PMID: 38777277 DOI: 10.1016/j.gie.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 02/10/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND AND AIMS Juvenile polyposis syndrome (JPS) is a rare hereditary autosomal dominant cancer-predisposition syndrome caused by germline pathogenic variants (PVs) located in SMAD4 or BMPR1A genes. Accurate clinical and endoscopic data regarding the evolution of gastric lesions remain sparse. METHODS Clinical, endoscopic, genetic, and pathologic data from patients with SMAD4 or BMPR1A PVs included between 2007 and 2020 in the French network on rare digestive polyposis (RENAPOL [French National Polyposis Register]) database were prospectively collected to address uncertainties regarding gastric involvement. RESULTS Thirty-six patients were included: 25 (69.5%) had SMAD4 PVs, and 11 had BMPR1A PVs. For SMAD4 PV carriers, median age at inclusion was 43.0 years (range, 10-78 years). At baseline EGD, 22 (88%) of 25 patients exhibited at least 1 gastric juvenile polyp, and 5 (20%) of 25 had macroscopic signs of inflammatory gastritis. Early gastric disease was mostly located under the cardia, then progressed to the gastric antrum and body. During a mean follow-up period of 55.0 months, 12 of 25 patients had gastric disease progression (ie, new juvenile polyps [91.6%], diffuse gastric involvement [41.6%], inflammatory flat progression [25%]). Among 62 biopsies, low-grade dysplasia was observed in 5 (7.5%) samples from 2 patients. Nine carriers (36%) underwent gastrectomy (mean age, 47.2 years) due to diffuse gastric involvement or worsening clinical symptoms. Gastric adenocarcinoma (T1) was found in 1 gastrectomy specimen. Among the 11 patients with BMPR1A PVs, 2 had gastric hamartomatomas at baseline EGD, none with dysplasia or symptoms. CONCLUSIONS Gastric involvement in JPS seems to be progressive over a lifetime, initiates in the cardia area, and mostly involves SMAD4 PV carriers.
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Affiliation(s)
- Marie Muller
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France.
| | | | - Nicolas Benech
- Department of Gastroenterology, GH Est Hospital, Lyon, France
| | - Mathieu Pioche
- Department of Gastroenterology, GH Est Hospital, Lyon, France
| | - Valérie Hervieu
- Department of Anatomopathology, Edouard Herriot Hospital, Lyon, France, Claude Bernard University, Hospices Civils de Lyon, Lyon, France
| | - Laura Calavas
- Department of Gastroenterology, GH Est Hospital, Lyon, France
| | - Maud Tusseau
- Genetics Department, Hospices Civils de Lyon (HCL), University Hospital, East Pathology Center, Lyon, France
| | - Sophie Dupuis-Girod
- Genetics Department, Hospices Civils de Lyon (HCL), University Hospital, East Pathology Center, Lyon, France
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Cohen S, Yerushalmy-Feler A, Rojas I, Phen C, Rudnick DA, Flahive CB, Erdman SH, Magen-Rimon R, Copova I, Attard T, Latchford A, Hyer W. Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden. J Pediatr Gastroenterol Nutr 2024; 79:161-167. [PMID: 38801072 DOI: 10.1002/jpn3.12257] [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: 03/24/2024] [Revised: 05/09/2024] [Accepted: 05/15/2024] [Indexed: 05/29/2024]
Abstract
OBJECTIVE A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS. METHODS Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group. RESULTS A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. CONCLUSIONS This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.
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Affiliation(s)
- Shlomi Cohen
- Tel Aviv Sourasky Medical Center, affiliated to the Faculty of Medicine, Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv University, Tel Aviv, Israel
| | - Anat Yerushalmy-Feler
- Tel Aviv Sourasky Medical Center, affiliated to the Faculty of Medicine, Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv University, Tel Aviv, Israel
| | - Isabel Rojas
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Claudia Phen
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - David A Rudnick
- Departments of Pediatrics and Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Colleen B Flahive
- Department of Pediatrics, Division of Gastroenterology Hepatology and Nutrition, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Steven H Erdman
- Department of Pediatrics, Division of Gastroenterology Hepatology and Nutrition, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Ramit Magen-Rimon
- Rambam Medical Center, Faculty of Medicine, Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Technion, Haifa, Israel
| | - Ivana Copova
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, University Hospital Motol and 2nd Faculty of Medicine, Prague, Czech Republic
| | - Thomas Attard
- Division of Gastroenterology, Hepatology and Nutrition, Children's Mercy Hospital Kansas City, The University of Missouri in Kansas City School of Medicine, Kansas City, Missouri, USA
| | - Andrew Latchford
- St Mark's Centre for Familial Intestinal Cancer, St Mark's Hospital, London, UK
- Department of Surgery and Cancer, Imperial College, London, UK
| | - Warren Hyer
- St Mark's Hospital, National Bowel Hospital, London, UK
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9
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Verma A, Kanneganti P, Kumar B, Upadhyaya VD, Mandelia A, Naik PB, Kumar T, Agarwal N. Peutz-Jeghers syndrome: management for recurrent intussusceptions. Pediatr Surg Int 2024; 40:148. [PMID: 38825635 DOI: 10.1007/s00383-024-05723-y] [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: 05/23/2024] [Indexed: 06/04/2024]
Abstract
BACKGROUND Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by hamartomatous gastrointestinal polyps along with the characteristic mucocutaneous freckling. Multiple surgeries for recurrent intussusception in these children may lead to short bowel syndrome. Here we present our experience of management in such patients. METHODS From January 2015 to December 2023, we reviewed children of PJS, presented with recurrent intussusceptions. Data were collected regarding presentation, management, and follow-up with attention on management dilemma. Diagnosis of PJS was based on criteria laid by World Health Organization (WHO). RESULTS A total of nine patients were presented with age ranging from 4 to 17 years (median 9 years). A total of eighteen laparotomies were performed (7 outside, 11 at our centre). Among 11 laparotomies done at our centre, resection and anastomosis of bowel was done 3 times while 8 times enterotomy and polypectomy was done after reduction of intussusception. Upper and lower gastrointestinal endoscopy (UGIE & LGIE) was done in all cases while intraoperative enteroscopy (IOE) performed when required. Follow-up ranged from 2 months to 7 years. CONCLUSION Children with PJS have a high risk of multiple laparotomies due to polyps' complications. Considering the diffuse involvement of the gut, early decision of surgery and extensive bowel resection should not be done. Conservative treatment must be tried under close observation whenever there is surgical dilemma. The treatment should be directed in the form of limited resection or polypectomy after reduction of intussusception.
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Affiliation(s)
- Anju Verma
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India.
| | | | - Basant Kumar
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India
| | | | - Ankur Mandelia
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India
| | - Prathibha B Naik
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India
| | - Tarun Kumar
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India
| | - Nishant Agarwal
- Department of Paediatric Surgery, SGPGIMS, Lucknow, 226014, India
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10
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Matsuyama S, Fukuda A, Matsumoto A, Eguchi H, Ueo T, Ohana M, Seno H. Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern. Clin J Gastroenterol 2024; 17:23-28. [PMID: 37950802 DOI: 10.1007/s12328-023-01884-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/19/2023] [Indexed: 11/13/2023]
Abstract
A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern.
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Affiliation(s)
- Sho Matsuyama
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan.
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Atsushi Matsumoto
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Hidetaka Eguchi
- Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8431, Japan
| | - Taro Ueo
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Masaya Ohana
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-Cho, Tenri, Nara, 632-8552, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
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11
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Sharma K, Sundling KE, Zhang R, Matkowskyj KA. Pathologic Features of Primary Colon, Rectal, and Anal Malignancies. Cancer Treat Res 2024; 192:233-263. [PMID: 39212924 DOI: 10.1007/978-3-031-61238-1_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
In USA, colorectal cancer is the third most commonly diagnosed cancer in men, second in women, as well as the third leading cause of cancer deaths (Siegel et al. in Cancer J Clin 73:1-112, 2023 [109]). Worldwide, colorectal cancer is the second leading cause of death and causes almost 916,000 deaths each year (Ferlay in Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon, 2020 [28]). Fortunately, due to the colon's surgical and endoscopic accessibility and functional redundancy, colorectal cancer is very treatable. Colonoscopic surveillance has the potential for not only providing tissue for the diagnosis of precancerous polyps and invasive carcinoma, but also preventing development of invasive carcinoma by the removal of precancerous lesions. This chapter discusses the clinical and pathologic features of the spectrum of epithelial, hematolymphoid, and mesenchymal malignant tumors of the colon, rectum, appendix, and anus.
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Affiliation(s)
- Kusum Sharma
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Kaitlin E Sundling
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
- Wisconsin State Laboratory of Hygiene, Madison, WI, USA
| | - Ranran Zhang
- Alberta Precision Laboratories, Grande Prairie Regional Hospital, Grande Prairie, Canada
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12
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Wu MY, Toon C, Field M, Wong M. Polyposis found on index colonoscopy in a 56-year-old female - BMPR1A variant in juvenile polyposis syndrome: A case report. World J Gastrointest Endosc 2023; 15:623-628. [PMID: 37900118 PMCID: PMC10600688 DOI: 10.4253/wjge.v15.i10.623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 07/21/2023] [Accepted: 07/31/2023] [Indexed: 10/12/2023] Open
Abstract
BACKGROUND Juvenile polyposis syndrome (JPS) is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene. It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults. Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up. CASE SUMMARY We report on the case of a 56-year-old female diagnosed with JPS after genetic testing revealed a rare variant of the BMPR1A gene BMPR1A c.1409T>C (p.Met470Thr). She was initially referred for colonoscopy by her general practitioner after testing positive on a screening faecal immunochemical test and subsequently found to have polyposis throughout the entire colorectum on her index screening colonoscopy. The patient was asymptomatic with a normal physical examination and no related medical or family history. Blood tests revealed only mild iron deficiency without anemia. To date, there has only been one other reported case of JPS with the same genetic variant. Subsequent colonoscopies were organised for complete polyp clearance and the patient was returned for surveillance follow-up. CONCLUSION JPS patients can present with no prior symptoms or family history. Genetic testing plays an important diagnostic role guiding management.
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Affiliation(s)
- Michael Yulong Wu
- Department of Gastroenterology and Hepatology, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
- Northern Clinical School, The University of Sydney, Sydney 2065, New South Wales, Australia
| | - Christopher Toon
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Michael Field
- Clinical Genetics, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - May Wong
- Department of Gastroenterology and Hepatology, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
- Northern Clinical School, The University of Sydney, Sydney 2065, New South Wales, Australia
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13
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Gofar K, Yearsley M, Gallardo M, Ghebrat HB, Chakraborty S. Colon Conundrum: A Fascinating Case Report Unraveling the Enigmatic Tactoid Bodies. Cureus 2023; 15:e45444. [PMID: 37859887 PMCID: PMC10583482 DOI: 10.7759/cureus.45444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/18/2023] [Indexed: 10/21/2023] Open
Abstract
Tactile corpuscle-like bodies (TCLBs) are specialized mechanoreceptors found in the dermal papilla of glabrous skin. They are normally not found in the gastrointestinal (GI) mucosa. There has been an increase in incidental detection in the GI mucosa due to the widespread use of colonoscopy procedures. However, TCLB's clinical implications in the GI tract remain unknown. We present a case of a 74-year-old man who was noted to have TCLBs in the rectosigmoid mucosa following resection for iatrogenic perforation. The TCLBs were spindle-shaped, positive for S-100, and negative for CD68. We review the literature on TCLBs in the GI tract and discuss their potential function in the GI mucosa.
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Affiliation(s)
- Kebire Gofar
- Gastroenterology, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Martha Yearsley
- Pathology, The Ohio State University College of Medicine, Columbus, USA
| | - Matthew Gallardo
- Internal Medicine, The Ohio State University College of Medicine, Columbus, USA
| | - Hermon B Ghebrat
- Internal Medicine, Afabet Community Hospital, Northern Red Sea Branch, Afabet, ERI
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14
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Caroleo AM, Rotulo S, Agolini E, Macchiaiolo M, Boccuto L, Antonelli M, Colafati GS, Cacchione A, Megaro G, Carai A, De Ioris MA, Lodi M, Tornesello A, Simone V, Torroni F, Cinalli G, Mastronuzzi A. SHH medulloblastoma and very early onset of bowel polyps in a child with PTEN hamartoma tumor syndrome. Front Mol Neurosci 2023; 16:1228389. [PMID: 37692099 PMCID: PMC10483120 DOI: 10.3389/fnmol.2023.1228389] [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: 05/24/2023] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a cancer predisposition syndrome characterized by an increased risk of developing benign and malignant tumors, caused by germline pathogenic variants of the PTEN tumour suppressor gene. PTEN gene variants often present in childhood with macrocephaly, developmental delay, and/or autism spectrum disorder while tumors and intestinal polyps are commonly detected in adults. PHTS is rarely associated with childhood brain tumors with only two reported cases of medulloblastoma (MB). We report the exceptional case of an infant carrying a germline and somatic pathogenic variant of PTEN and a germline and somatic pathogenic variant of CHEK2 who developed a MB SHH in addition to intestinal polyposis.
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Affiliation(s)
- Anna Maria Caroleo
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Silvia Rotulo
- Department of Pediatrics, Sapienza University of Rome, Rome, Italy
| | - Emanuele Agolini
- Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Marina Macchiaiolo
- Rare Diseases and Medical Genetics Unit, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Luigi Boccuto
- School of Nursing, College of Behavioral, Social and Health Sciences Healthcare Genetics Interdisciplinary Doctoral Program, Clemson University, Clemson, SC, United States
| | - Manila Antonelli
- Faculty of Medicine and Dentistry, Department of Radiological, Oncological, and Pathological Anatomy Sciences, Sapienza University of Rome, Rome, Italy
| | | | - Antonella Cacchione
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Giacomina Megaro
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Andrea Carai
- Neurosurgery Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Maria Antonietta De Ioris
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | - Mariachiara Lodi
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
| | | | - Valeria Simone
- Pediatric Oncology Unit, Ospedale Vito Fazzi, Lecce, Italy
| | - Filippo Torroni
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | - Giuseppe Cinalli
- Pediatric Neurosurgery Unit, Department of Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
| | - Angela Mastronuzzi
- Department of Onco-Hematology, Cell Therapy, Gene Therapy and Hemopoietic Transplant, Bambino Gesù Children’s Hospital (IRCCS), Rome, Italy
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15
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Nagai K, Fuchizaki U, Ueda Y. Solitary juvenile polyp of the rectum with intramucosal adenocarcinoma. Clin J Gastroenterol 2023:10.1007/s12328-023-01798-7. [PMID: 37067731 DOI: 10.1007/s12328-023-01798-7] [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: 03/16/2023] [Accepted: 03/30/2023] [Indexed: 04/18/2023]
Abstract
We describe a case of solitary juvenile polyp of the rectum with intramucosal adenocarcinoma. A 55-year-old man presented to our hospital for evaluation after a positive fecal occult blood test. Colonoscopy revealed a pedunculated polyp of 25 mm in size which has an irregular shape and pale red color on the rectum. The polyp had a proliferation of blood vessels and an invisible surface pattern. Endoscopic mucosal resection was performed. Pathologically, it was diagnosed as a solitary juvenile polyp with intramucosal well-differentiated adenocarcinoma. When we encounter juvenile polyps, the possibility of malignancy should be taken into consideration for treatment.
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Affiliation(s)
- Kazuki Nagai
- Department of Gastroenterology, Kahoku Central Hospital, Tsubata, Ishikawa, 929-0323, Japan.
| | - Uichiro Fuchizaki
- Department of Gastroenterology, Kahoku Central Hospital, Tsubata, Ishikawa, 929-0323, Japan
| | - Yoshimichi Ueda
- Department of Pathology, Keiju Medical Center, Nanao, Ishikawa, 926-8605, Japan
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16
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Singh AD, Gupta A, Mehta N, Heald B, Macaron C, Liska D, Bhatt A, Burke CA. Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis. Gastrointest Endosc 2023; 97:407-414.e1. [PMID: 36265529 DOI: 10.1016/j.gie.2022.10.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 09/15/2022] [Accepted: 10/10/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better assess this, we conducted a systematic review and meta-analysis. METHODS MEDLINE, Embase, and Scopus databases were searched for the key words juvenile polyposis syndrome, juvenile polyps, stomach cancer, GC, SMAD4, BMPR1A, hamartomatous polyposis syndrome, hamartomas, and hereditary cancers for studies reporting upper GI manifestations in JPS. The primary outcome was the reported occurrence of GC in JPS. We then compared GC occurrence based on the presence or absence of pathogenic germline variants (PGVs) and in untested patients. RESULTS Eleven studies including 637 patients were included. The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8-5.2; I2 = 12.3%) at a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC in patients with SMAD4 PGV was 10.1% (95% CI, 3.2-16.8%; I2 = 54.7%). GC was reported in only 1 BMPR1A PGV carrier and was not reported in patients without an identifiable PGV. In patients with prior germline testing, the risk of GC was higher in SMAD4 PGV carriers (odds ratio, 11.6; 95% CI, 4.6-29.4; I2 = 18.3%) compared with patients without SMAD4 PGV. In JPS patients with unknown status of germline testing, pooled occurrence of GC was 7.5% (95% CI, 0-15.5). There was an overall moderate risk of bias in the studies. CONCLUSIONS GC is highest in SMAD4-associated JPS and was not reported in patients without identifiable PGVs. The value of GC surveillance in BMPR1A PGV carriers and JPS patients without an identifiable PGV is questionable. Germline testing should be performed in all JPS patients to inform GC risk discussion and utility of surveillance.
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Affiliation(s)
- Achintya D Singh
- Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA
| | - Akshita Gupta
- Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Neal Mehta
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Brandie Heald
- Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, Ohio, USA; Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Carole Macaron
- Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - David Liska
- Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amit Bhatt
- Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Carol A Burke
- Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
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17
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Gorji L, Albrecht P. Hamartomatous polyps: Diagnosis, surveillance, and management. World J Gastroenterol 2023; 29:1304-1314. [PMID: 36925460 PMCID: PMC10011967 DOI: 10.3748/wjg.v29.i8.1304] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/08/2022] [Accepted: 02/16/2023] [Indexed: 02/28/2023] Open
Abstract
Hereditary polyposis syndrome can be divided into three categories: Ade-nomatous, serrated, and hamartomatous polyps. Hamartomatous polyps, malformations of normal tissue presenting in a disorganized manner, are characterized by an autosomal dominant inheritance pattern. These syndromes exhibit hamartomatous gastrointestinal polyps in conjunction to extra-intestinal manifestations, which require conscientious and diligent monitoring. Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS). Diagnosis can be pursued with molecular testing and endoscopic sampling. Early identification of these autosomal dominant pathologies allows to optimize malignancy sur-veillance, which helps reduce morbidity and mortality in both the affected patient population as well as at-risk family members. Endoscopic surveillance is an important pillar of prognosis and monitoring, with many patients eventually requiring surgical intervention. In this review, we discuss the diagnosis, surveillance, and management of HPS.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
| | - Peter Albrecht
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
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18
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Pedrazzani C, Conti C, Di Vittori A, Turri G, Bernardoni L, Mafficini A, Luchini C, Gabbrielli A, Scarpa A, Guglielmi A. Video technical notes for approaching a unique case of Juvenile Polyposis with massive gastric ingrowth. Asian J Surg 2023; 46:924-925. [PMID: 35918225 DOI: 10.1016/j.asjsur.2022.07.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 07/15/2022] [Indexed: 02/08/2023] Open
Affiliation(s)
- Corrado Pedrazzani
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy.
| | - Cristian Conti
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Angelo Di Vittori
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Giulia Turri
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
| | - Laura Bernardoni
- Digestive Endoscopy Unit, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Andrea Mafficini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Armando Gabbrielli
- Digestive Endoscopy Unit, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Alfredo Guglielmi
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
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19
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Delgado PE, Medas R, Trindade E, Martínez EPC. Capsule endoscopy: wide clinical scope. ARTIFICIAL INTELLIGENCE IN CAPSULE ENDOSCOPY 2023:21-51. [DOI: 10.1016/b978-0-323-99647-1.00004-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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20
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Limpias Kamiya KJL, Hosoe N, Takabayashi K, Okuzawa A, Sakurai H, Hayashi Y, Miyanaga R, Sujino T, Ogata H, Kanai T. Feasibility and Safety of Endoscopic Ischemic Polypectomy and Clinical Outcomes in Patients with Peutz-Jeghers Syndrome (with Video). Dig Dis Sci 2023; 68:252-258. [PMID: 35394591 DOI: 10.1007/s10620-022-07477-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 01/30/2022] [Indexed: 02/01/2023]
Abstract
OBJECTIVES Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease with a clinical features related to gastrointestinal (GI) hamartomatous polyposis, frequently observed in the small bowel. Balloon-assisted enteroscopy (BAE) has made non-surgical treatment of GI polyps possible. Endoscopic mucosal resection (EMR) has been performed but was associated with complications and difficulties. Recently, endoscopic ischemic polypectomy (EIP) has been developed and its usefulness reported. The study evaluated the feasibility and safety of EIP and the clinical outcomes of patients with PJS. METHODS We retrospectively collected data of consecutive patients with PJS between September 2009 and March 2021. Data regarding clinical characteristics, follow-up methods, endoscopic management, and complications were collected. EIP feasibility and safety were assessed. RESULTS Twenty-two patients were included. The observation period was 70 months (range, 5-153). Of the 124 therapeutic endoscopy procedures performed, 68 used BAE. Of the 607 polyps treated, 329 polyps were located in the small bowel. EIP was able to treat a greater number of polyps per patient than EMR (P < 0.003), without any complications, carcinoma, or intussusception in the small bowel (P < 0.001). During the follow-up period, 3 patients developed GI cancer. CONCLUSION Long-term follow-up in patients with PJS showed that EIP was a feasible and safe technique.
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Affiliation(s)
- Kenji J L Limpias Kamiya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
| | - Kaoru Takabayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Anna Okuzawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hinako Sakurai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yukie Hayashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Ryoichi Miyanaga
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tomohisa Sujino
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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21
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Mafficini A, Brosens LAA, Piredda ML, Conti C, Mattiolo P, Turri G, Mastrosimini MG, Cingarlini S, Crinò SF, Fassan M, Piccoli P, Simbolo M, Nottegar A, Lawlor RT, Guglielmi A, Scarpa A, Pedrazzani C, Luchini C. Juvenile polyposis diagnosed with an integrated histological, immunohistochemical and molecular approach identifying new SMAD4 pathogenic variants. Fam Cancer 2022; 21:441-451. [PMID: 35075588 PMCID: PMC9636285 DOI: 10.1007/s10689-022-00289-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 01/12/2022] [Indexed: 01/07/2023]
Abstract
Juvenile polyposis (JP) is a rare familial syndrome characterized by the development of numerous hamartomatous polyps of the gastrointestinal tract and by an increased risk of developing gastrointestinal cancers. It follows a pattern of autosomal dominant inheritance and is associated with germline variants of SMAD4 or BMPR1A genes. Differential diagnosis may be difficult based on histology alone, due to morphological similarities to other familial syndromes. Here we report a case of familial JP diagnosed in a 50-years woman with a familial history positive for gastrointestinal cancers and other tumor types. The patient presented with severe iron deficiency anemia and showed numerous polyps in the stomach and jejunum according to endoscopy and imaging. She underwent an intra-gastric laparoscopic removal of the major gastric polyp, followed by jejunal exploration and resection of a segment with multiple neoformations. Histological examination revealed the presence of hamartomatous polyposis. Gastric and intestinal samples were analyzed with next-generation sequencing. Molecular analysis showed that the patient harbored a germline splicing site variant of SMAD4, c.1139 + 3A > G, which was complemented by different somatic variants of the same gene in the different polyps. Immunohistochemistry for SMAD4 confirmed loss of protein expression in the polyps, with regular expression in normal cells. cDNA sequencing further confirmed the findings. We thus definitively diagnosed the woman as having JP thanks to an integrated approach based on histology, immunohistochemistry and molecular analysis. The identified variants, all previously reported as variants of unknown significance, were classified as pathogenic as they complemented each other leading to SMAD4 loss.
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Affiliation(s)
- Andrea Mafficini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Lodewijk A A Brosens
- Department of Pathology, Utrecht, and Department of Pathology, University Medical Center Utrecht, Utrecht University, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maria L Piredda
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Cristian Conti
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Giulia Turri
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Maria G Mastrosimini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Sara Cingarlini
- Department of Medicine, Section of Oncology, University and Hospital Trust of Verona, Verona, Italy
| | - Stefano F Crinò
- Digestive Endoscopy Unit, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, and Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Paola Piccoli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Michele Simbolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Alessia Nottegar
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Rita T Lawlor
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Alfredo Guglielmi
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Corrado Pedrazzani
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University and Hospital Trust of Verona, 37134, Verona, Italy.
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy.
- ARC-Net Research Center, University of Verona, Verona, Italy.
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22
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Zhao M, Lin X, Fang Y, Zhuang A, Tong H, Lu W, Zhou Y, Zhang Y. Case Report: Duodenal Carcinoma in a 40-Year-Old Asian Man With Cowden Syndrome. Front Surg 2022; 9:935048. [PMID: 35903259 PMCID: PMC9320325 DOI: 10.3389/fsurg.2022.935048] [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: 05/03/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Cowden syndrome is a rare autosomal dominant genetic disease associated with PTEN mutation and is mainly shown as systemic multisystem lesions. The incidence of adenocarcinoma of the duodenum with Cowden syndrome in Asian males is rare. We hereby describe the diagnosis, treatment, and prognosis of a patient with duodenal carcinoma and Cowden syndrome. CASE DESCRIPTION A 40-year-old Chinese man was hospitalized because of gastrointestinal hemorrhage and anemia due to infiltrating adenocarcinoma of the descending part of the duodenum. He also had typical signs of Cowden syndrome, such as multiple polyps of the gastrointestinal tract, macrocephaly, papilloma of the tongue, soles hyperkeratosis, and melanosis spots. After the pancreaticoduodenectomy (classic Whipple), the lesions revealed the presence of hamartomatoid polyps, and some of them mutated into non-mucinous adenocarcinoma (80%) and mucinous adenocarcinoma (20%). Further investigation showed a lack of PTEN protein expression in the duodenal neoplasm, and genetic analysis showed the mutation of p.E242fs in PTEN. The patient was followed up for 1 year. There was no appearance of recurrence or distant metastasis. CONCLUSION It is suggested that we should pay more attention to the differential diagnosis of duodenal carcinoma combined with gastrointestinal polyps. If multiple gastrointestinal polyps with gastrointestinal bleeding are encountered, Cowden syndrome should be considered, and timely diagnosis and treatment should be implemented.
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Affiliation(s)
- Mingkun Zhao
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xiaohan Lin
- School of Clinical Medicine, Hangzhou Normal University, Hangzhou, China
| | - Yuan Fang
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Aobo Zhuang
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Hanxing Tong
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weiqi Lu
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuhong Zhou
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Zhang
- Department of General Surgery, South Hospital of the Zhongshan Hospital/Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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23
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Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ. Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2022; 162:2063-2085. [PMID: 35487791 DOI: 10.1053/j.gastro.2022.02.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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Affiliation(s)
- C Richard Boland
- Division of Gastroenterology, University of California-San Diego School of Medicine, San Diego, California
| | - Gregory E Idos
- Divisions of Gastroenterology and Clinical Cancer Genomics, Center for Precision Medicine, City of Hope National Medical Center, Duarte, California
| | - Carol Durno
- The Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Francis M Giardiello
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph C Anderson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; University of Connecticut, Farmington, Connecticut
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Jason A Dominitz
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | - Seth Gross
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
| | - Samir Gupta
- Veterans Affairs Medical Center, San Diego, California; University of California San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, San Diego, California
| | - Brian C Jacobson
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Swati G Patel
- University of Colorado School of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Aasma Shaukat
- Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota
| | - Sapna Syngal
- Brigham and Women's Hospital, Boston Massachusetts; Dana-Farber Cancer Institute, Boston Massachusetts; Harvard Medical School, Boston Massachusetts
| | - Douglas J Robertson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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24
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Boland CR, Idos GE, Durno C, Giardiello FM, Anderson JC, Burke CA, Dominitz JA, Gross S, Gupta S, Jacobson BC, Patel SG, Shaukat A, Syngal S, Robertson DJ. Diagnosis and management of cancer risk in the gastrointestinal hamartomatous polyposis syndromes: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2022; 95:1025-1047. [PMID: 35487765 DOI: 10.1016/j.gie.2022.02.044] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This U.S. Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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Affiliation(s)
- C Richard Boland
- Division of Gastroenterology, University of California-San Diego School of Medicine, San Diego, California.
| | - Gregory E Idos
- Divisions of Gastroenterology and Clinical Cancer Genomics, Center for Precision Medicine, City of Hope National Medical Center, Duarte, California
| | - Carol Durno
- The Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Francis M Giardiello
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph C Anderson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; University of Connecticut, Farmington, Connecticut
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Jason A Dominitz
- Veterans Affairs Puget Sound Health Care System, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington
| | - Seth Gross
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York
| | - Samir Gupta
- Veterans Affairs Medical Center, San Diego, California; University of California San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, San Diego, California
| | - Brian C Jacobson
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Swati G Patel
- University of Colorado School of Medicine, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Aasma Shaukat
- Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; University of Minnesota, Minneapolis, Minnesota
| | - Sapna Syngal
- Brigham and Women's Hospital, Boston Massachusetts; Dana-Farber Cancer Institute, Boston Massachusetts; Harvard Medical School, Boston Massachusetts
| | - Douglas J Robertson
- Veterans Affairs Medical Center, White River Junction, Vermont; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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25
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Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2022; 117:846-864. [PMID: 35471415 DOI: 10.14309/ajg.0000000000001755] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 12/11/2022]
Abstract
The gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with an increased risk of benign and malignant intestinal and extraintestinal tumors. They include Peutz-Jeghers syndrome, juvenile polyposis syndrome, the PTEN hamartoma tumor syndrome (including Cowden's syndrome and Bannayan-Riley-Ruvalcaba syndrome), and hereditary mixed polyposis syndrome. Diagnoses are based on clinical criteria and, in some cases, confirmed by demonstrating the presence of a germline pathogenic variant. The best understood hamartomatous polyposis syndrome is Peutz-Jeghers syndrome, caused by germline pathogenic variants in the STK11 gene. The management is focused on prevention of bleeding and mechanical obstruction of the small bowel by polyps and surveillance of organs at increased risk for cancer. Juvenile polyposis syndrome is caused by a germline pathogenic variant in either the SMAD4 or BMPR1A genes, with differing clinical courses. Patients with SMAD4 pathogenic variants may have massive gastric polyposis, which can result in gastrointestinal bleeding and/or protein-losing gastropathy. Patients with SMAD4 mutations usually have the simultaneous occurrence of hereditary hemorrhagic telangiectasia (juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia overlap syndrome) that can result in epistaxis, gastrointestinal bleeding from mucocutaneous telangiectasias, and arteriovenous malformations. Germline pathogenic variants in the PTEN gene cause overlapping clinical phenotypes (known as the PTEN hamartoma tumor syndromes), including Cowden's syndrome and related disorders that are associated with an increased risk of gastrointestinal and colonic polyposis, colon cancer, and other extraintestinal manifestations and cancers. Due to the relative rarity of the hamartomatous polyposis syndromes, recommendations for management are based on few studies. This US Multi-Society Task Force on Colorectal Cancer consensus statement summarizes the clinical features, assesses the current literature, and provides guidance for diagnosis, assessment, and management of patients with the hamartomatous polyposis syndromes, with a focus on endoscopic management.
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26
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Dal Buono A, Gaiani F, Poliani L, Laghi L. Juvenile polyposis syndrome: An overview. Best Pract Res Clin Gastroenterol 2022; 58-59:101799. [PMID: 35988962 DOI: 10.1016/j.bpg.2022.101799] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 03/13/2022] [Accepted: 03/23/2022] [Indexed: 01/31/2023]
Abstract
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
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Affiliation(s)
- Arianna Dal Buono
- Division of Gastroenterology, Department of Gastroenterology, Humanitas Research Hospital - IRCCs, Rozzano, Milan, Italy
| | - Federica Gaiani
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Laura Poliani
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Luigi Laghi
- Department of Medicine and Surgery, University of Parma, Parma, Italy; Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy.
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27
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Toss A, Quarello P, Mascarin M, Banna GL, Zecca M, Cinieri S, Peccatori FA, Ferrari A. Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group. Curr Oncol Rep 2022; 24:843-860. [PMID: 35320498 PMCID: PMC9170630 DOI: 10.1007/s11912-022-01213-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/18/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW The present narrative systematic review summarizes current knowledge on germline gene mutations predisposing to solid tumors in adolescents and young adults (AYAs). RECENT FINDINGS AYAs with cancer represent a particular group of patients with specific challenging characteristics and yet unmet needs. A significant percentage of AYA patients carry pathogenic or likely pathogenic variants (PV/LPVs) in cancer predisposition genes. Nevertheless, knowledge on spectrum, frequency, and clinical implications of germline variants in AYAs with solid tumors is limited. The identification of PV/LPV in AYA is especially critical given the need for appropriate communicative strategies, risk of second primary cancers, need for personalized long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. Moreover, these gene alterations may potentially provide novel biomarkers and therapeutic targets that are lacking in AYA patients. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PV/LPVs supports a role for genetic counseling and testing irrespective of tumor type.
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Affiliation(s)
- Angela Toss
- Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Paola Quarello
- Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy
- Department of Public Health and Paediatric Sciences, University of Torino, Turin, Italy
| | - Maurizio Mascarin
- AYA Oncology and Pediatric Radiotherapy Unit, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Giuseppe Luigi Banna
- Candiolo Cancer Institute, FPO-IRCCS, SP142, km 3.95, 10060, Candiolo, Turin, Italy.
| | - Marco Zecca
- Department of Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Saverio Cinieri
- Medical Oncology Unit and Breast Unit Ospedale Perrino ASL, Brindisi, Italy
| | - Fedro Alessandro Peccatori
- Fertility and Procreation Unit, Gynecologic Oncology Program, European Institute of Oncology IRCCS, Milan, Italy
| | - Andrea Ferrari
- Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
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28
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Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis. Cancers (Basel) 2022; 14:cancers14030628. [PMID: 35158896 PMCID: PMC8833640 DOI: 10.3390/cancers14030628] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/22/2022] [Accepted: 01/23/2022] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of molecular test results. Genetic predisposition to colorectal cancer (CRC) should be suspected mainly in young patients, in patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. The aim of this review is to describe the main nonmalignant comorbidities associated with selected CRC predisposition syndromes that may serve as valuable diagnostic clues for clinicians and genetic professionals. Abstract Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.
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Katz LH, Gingold-Belfer R, Vainer E, Hegger S, Laish I, Derazne E, Weintraub I, Reznick-Levi G, Goldberg Y, Levi Z, Cohen S, Half EE. Phenotypic diversity among juvenile polyposis syndrome patients from different ethnic background. Hered Cancer Clin Pract 2022; 20:2. [PMID: 35057835 PMCID: PMC8772101 DOI: 10.1186/s13053-021-00207-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/07/2021] [Indexed: 11/29/2022] Open
Abstract
Abstract Juvenile polyposis syndrome (JPS), has diverse phenotypes. Aim: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities. Methods Patients’ data were extracted retrospectively from 5 centers. Results Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 4\14 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017). Conclusions We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.
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Mitra S, Paramaguru R, Das P, Katti SV. Preneoplastic Lesions and Polyps of the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:593-698. [DOI: 10.1007/978-981-16-6395-6_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Patel N, Das P, Jain D. Systemic Manifestations of Gastrointestinal Tract Diseases and Systemic Diseases Involving the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:521-572. [DOI: 10.1007/978-981-16-6395-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Intussusception in Peutz-Jeghers Syndrome: Management of Unusual Acute Abdominal Presentation. Indian J Surg Oncol 2021; 13:262-266. [DOI: 10.1007/s13193-021-01448-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/01/2021] [Indexed: 11/25/2022] Open
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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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Ma YR, Polydorides AD. Clinicopathologic Characteristics and Neoplasia Risk of Colorectal Inflammatory Polyposis in Inflammatory Bowel Disease. Arch Pathol Lab Med 2021; 146:172-181. [PMID: 33946102 DOI: 10.5858/arpa.2020-0745-oa] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2021] [Indexed: 11/11/2022]
Abstract
CONTEXT.— Inflammatory polyps (IPs) in inflammatory bowel disease may have been associated in the past with increased neoplasia risk. Additionally, colonic mucosa in filiform polyposis and giant inflammatory polyposis may be difficult to visualize during endoscopic surveillance, perhaps contributing to early colectomy in these patients. OBJECTIVE.— To examine the clinicopathologic characteristics and significance of IPs and inflammatory polyposis in inflammatory bowel disease. DESIGN.— We identified 336 resections from inflammatory bowel disease patients (212 [63.1%] male; mean age, 40.3 years; 175 [52.1%] with ulcerative colitis), including 78 with rare/few (<10) IPs, 141 with multiple (≥10) IPs, and 117 with inflammatory polyposis (including 30 with filiform polyposis/giant inflammatory polyposis) and compared them with 100 controls without IPs along various parameters, including overall and occult (unexpected) dysplasia. RESULTS.— There was no increased neoplasia in resections with IPs compared with controls, given similar age, disease duration, degree of inflammation, anatomical extent of colitis, prevalence of primary sclerosing cholangitis, and tissue sampling. Increasing numbers of IPs and inflammatory polyposis were significantly associated in multivariate analysis with ulcerative and indeterminate colitis (P = .003) and shorter disease duration (P = .01), but also, and independently, with lower rates of dysplasia overall, including all grades (P = .001) and advanced neoplasia (P = .04). There were no instances of occult dysplasia (any grade) among inflammatory polyposis cases. CONCLUSIONS.— These findings support the conclusion that the presence of IPs per se, and inflammatory polyposis in particular (including filiform polyposis and giant inflammatory polyposis), should not be considered an independent risk factor for the development of neoplasia in inflammatory bowel disease patients, outside the context of disease duration and inflammatory burden.
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Affiliation(s)
- Yihong R Ma
- From the Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.,Ma is now at West Florida Hospital in Pensacola
| | - Alexandros D Polydorides
- From the Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
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Abstract
PURPOSE OF REVIEW Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients. RECENT FINDINGS A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence. SUMMARY Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.
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Affiliation(s)
- Ilja Tacheci
- 2nd Department of Internal Medicine - Gastroenterology, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital, Hradec Kralove, Czech Republic
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Abstract
Purpose of review Gastric cancer is a leading cause of cancer death in the world. Between 1% and 3% of cases are associated with specific genetic cancer risk syndromes. The purpose of this article is to review the latest insights, as well as gaps in knowledge, regarding some of the most common hereditary gastric cancer syndromes: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Lynch syndrome, the adenomatous polyposis syndromes, and the hamartomatous polyposis syndromes. Recent findings Patients carrying pathogenic variants in CDH1, but not meeting clinical criteria for HDGC, are increasingly being identified thanks to multigene panel testing; their absence from previous analyses overestimated gastric cancer penetrance. GAPPS is a recently described hereditary gastric cancer syndrome associated with specific point mutations in the promoter 1B region of the APC gene. Summary Risk of gastric cancer is highest among carriers of pathogenic variants in CDH1, with cumulative incidences approximately 40% and 30% for men and women, respectively. Mutations associated with Lynch syndrome and adenomatous polyposis syndromes confer greatest risk for gastric cancer in East Asian populations. Risk of gastric cancer in GAPPS and hamartomatous polyposis syndromes is difficult to estimate due to their rarity, but mutation status likely determines risk. Future research is needed to more precisely define risk of gastric cancer in these syndromes, so strategies for screening and prophylactic gastrectomy can be optimized.
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Shen N, Wang X, Lu Y, Xiao F, Xiao J. Importance of early detection of juvenile polyposis syndrome: A case report and literature review. Medicine (Baltimore) 2020; 99:e23494. [PMID: 33327285 PMCID: PMC7738017 DOI: 10.1097/md.0000000000023494] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Juvenile polyposis syndrome (JPS) is a rare genetic gastrointestinal disorder with hidden and variable clinical features. Early detection is crucial for good prognosis. PATIENT CONCERNS A 20-year-old female went to hospital for fever, and was unexpectedly diagnosed as JPS during treatment. She reported no clinical signs or family history of JPS. DIAGNOSIS Blood routine examination on hospital admission suggested a moderate anemia. Bone marrow cytology and leukemia fusion gene test were performed to rule out leukemia. Other examinations including ultrasound and computed tomography were also conducted for differential diagnosis. Further electronic colonoscopy identified more than 20 pedicle polyps located at her ileocecum and rectum. Mutation analysis detected a novel de novo pathogenic variant, c.910C>T (p.Gln304Ter) within bone morphogenetic protein receptor type 1A gene, establishing the diagnosis of JPS. INTERVENTIONS The patient was treated with endoscopic interventions. We also provided a genetic counseling for this family. OUTCOMES The patient's polyps were removed, some of which already had adenomatous changes. The patient received surveillance of hereditary colorectal cancer according to guidelines. LESSONS Variable features and lack of family history probably lead to a great underestimation of potential JPS population. It is recommended to perform genetic testing by a multigene panel in individuals who have suspected symptoms of polyposis.
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Affiliation(s)
- Na Shen
- Department of Laboratory Medicine
| | | | | | | | - Juan Xiao
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Sinha A, Johal AS, Khurana A, Basi P, Khara HS. Retrograde NaviAid Enteroscopy-Assisted Resection of Distal Small Bowel Hamartomatous Polyps. Cureus 2020; 12:e11962. [PMID: 33425538 PMCID: PMC7790320 DOI: 10.7759/cureus.11962] [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: 12/07/2020] [Indexed: 11/19/2022] Open
Abstract
Hamartomatous polyps are gastrointestinal tumors that may present with small bowel obstruction requiring surgical resection, while others may present earlier as symptomatic anemia prior to becoming an obstructing mass. Video capsule endoscopy has enhanced the early detection of small bowel lesions. However, endoscopic interventions especially for distal small bowel lesions are limited due to long procedure times, technical challenges in achieving depth of insertion, and the requirement of specialized deep enteroscopy equipment with advanced endoscopy training, which are not always available. Therefore, surgical intervention is often required. NaviAid-assisted enteroscopy, a novel thorough-the-scope balloon, results in deep anterograde and retrograde intubation of the small intestine using standard colonoscope and can be used for rapid therapeutic intervention. We present two cases of distal small bowel hamartomas which were resected via retrograde NaviAid-assisted enteroscopy, thus, preventing surgery.
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Affiliation(s)
- Ayusa Sinha
- Division of Gastroenterology and Nutrition, Geisinger Health System, Danville, USA
| | - Amitpal S Johal
- Division of Gastroenterology and Nutrition, Geisinger Health System, Danville, USA
| | - Ansh Khurana
- Division of Gastroenterology and Nutrition, Geisinger Health System, Danville, USA
| | - Puneet Basi
- Department of Gastroenterology, UPMC Susquehanna Health, Williamsport, USA
| | - Harshit S Khara
- Division of Gastroenterology and Nutrition, Geisinger Health System, Danville, USA
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Sputa‐Grzegrzolka P, Wozniak Z, Akutko K, Pytrus T, Baran W, Calik J, Glatzel‐Plucinska N, Domagala Z, Podhorska‐Okolow M, Stawarski A, Dziegiel P. Laugier‐Hunziker syndrome: a case report of the pediatric patient and review of the literature. Int J Dermatol 2020; 59:1513-1519. [DOI: 10.1111/ijd.15262] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/12/2020] [Accepted: 09/23/2020] [Indexed: 02/06/2023]
Affiliation(s)
| | | | - Katarzyna Akutko
- 2nd Department and Clinic of Pediatrics, Gastroenterology and Nutrition Wroclaw Medical University Poland
| | - Tomasz Pytrus
- 2nd Department and Clinic of Pediatrics, Gastroenterology and Nutrition Wroclaw Medical University Poland
| | - Wojciech Baran
- Department of Dermatology, Venereology and Allergology Wroclaw Medical University Poland
| | - Jacek Calik
- Department of ChemotherapyLower Silesian Oncology Center Wroclaw Poland
| | - Natalia Glatzel‐Plucinska
- Division of Histology and Embryology Department of Human Morphology and Embryology Wroclaw Medical University Poland
| | - Zygmunt Domagala
- Division of Anatomy Department of Human Morphology and Embryology Wroclaw Medical University Poland
| | | | - Andrzej Stawarski
- 2nd Department and Clinic of Pediatrics, Gastroenterology and Nutrition Wroclaw Medical University Poland
| | - Piotr Dziegiel
- Division of Histology and Embryology Department of Human Morphology and Embryology Wroclaw Medical University Poland
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Liu Q, Liu M, Liu T, Yu Y. Familial juvenile polyposis syndrome with a de novo germline missense variant in BMPR1A gene: a case report. BMC MEDICAL GENETICS 2020; 21:196. [PMID: 33032550 PMCID: PMC7545562 DOI: 10.1186/s12881-020-01135-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 09/28/2020] [Indexed: 11/10/2022]
Abstract
Background Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. Case presentation Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband’s children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusions Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.
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Affiliation(s)
- Qing Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Mengling Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Yiyi Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
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Edris Sharif Rahmani, Azarpara H, Abazari MF, Mohajeri MR, Nasimi M, Ghorbani R, Azizpour A, Rahimi H. Novel Mutation C.7348C>T in NF1 Gene Identified by Whole-Exome Sequencing in Patient with Overlapping Clinical Symptoms of Neurofibromatosis Type 1 and Bannayan–Riley–Ruvalcaba Syndrome. CYTOL GENET+ 2020. [DOI: 10.3103/s0095452720040106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Schubert SA, Morreau H, de Miranda NFCC, van Wezel T. The missing heritability of familial colorectal cancer. Mutagenesis 2020; 35:221-231. [PMID: 31605533 PMCID: PMC7352099 DOI: 10.1093/mutage/gez027] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 09/05/2019] [Indexed: 02/06/2023] Open
Abstract
Pinpointing heritability factors is fundamental for the prevention and early detection of cancer. Up to one-quarter of colorectal cancers (CRCs) occur in the context of familial aggregation of this disease, suggesting a strong genetic component. Currently, only less than half of the heritability of CRC can be attributed to hereditary syndromes or common risk loci. Part of the missing heritability of this disease may be explained by the inheritance of elusive high-risk variants, polygenic inheritance, somatic mosaicism, as well as shared environmental factors, among others. A great deal of the missing heritability in CRC is expected to be addressed in the coming years with the increased application of cutting-edge next-generation sequencing technologies, routine multigene panel testing and tumour-focussed germline predisposition screening approaches. On the other hand, it will be important to define the contribution of environmental factors to familial aggregation of CRC incidence. This review provides an overview of the known genetic causes of familial CRC and aims at providing clues that explain the missing heritability of this disease.
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Affiliation(s)
- Stephanie A Schubert
- Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Hans Morreau
- Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Noel F C C de Miranda
- Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Tom van Wezel
- Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
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Cortegoso Valdivia P, Rondonotti E, Pennazio M. Safety and efficacy of an enteroscopy-based approach in reducing the polyp burden in patients with Peutz-Jeghers syndrome: experience from a tertiary referral center. Ther Adv Gastrointest Endosc 2020; 13:2631774520919369. [PMID: 32705081 PMCID: PMC7359414 DOI: 10.1177/2631774520919369] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 03/12/2020] [Indexed: 12/30/2022] Open
Abstract
Background: Patients with Peutz–Jeghers syndrome develop hamartomatous polyps in the small bowel, possibly causing anemia, intussusception, and obstruction. We aimed to evaluate the impact of an enteroscopy-based approach, including both device-assisted and intraoperative enteroscopy, on the reduction of the polyp burden in a cohort of adult Peutz–Jeghers syndrome patients. Materials and methods: A retrospective study was conducted at Azienda Ospedaliero-Universitaria Città della Salute e della Scienza in Turin, Italy. Consecutive Peutz–Jeghers syndrome patients eligible for device-assisted or intraoperative enteroscopy, between January 2003 and November 2019, were included. Enteroscopy technical issues and complications were recorded. At the time of index enteroscopy, the patients’ clinical records were retrospectively reviewed, and clinical data were recorded until November 2019. Results: Overall, 24 patients were included. Before inclusion, 16/24 patients (66.7%) underwent small bowel surgery for polyp-related complications, 13 of which (81.2%) in an emergent setting. Two patients had a history of small bowel neoplasms. During the timeframe, 47 device-assisted enteroscopies and 9 intraoperative enteroscopies were performed, and 247 small bowel polyps were endoscopically removed. The overall complication rate was 12.8% (8.5% for device-assisted enteroscopy, 22.2% for intraoperative enteroscopy). The median observation time was 108 months: in this timeframe, two patients developed small bowel polyp-related complications requiring emergent surgery. No patients developed small bowel cancer, but nine extra-gastrointestinal neoplasms were recorded. Conclusion: An enteroscopy-based approach appears to be well tolerated and effective in decreasing polyp-related complications in Peutz–Jeghers syndrome patients, thus reducing the need for emergent surgery. Although the prevention of small bowel polyp-related complications remains the main goal in these patients, the high incidence of extra-gastrointestinal neoplasms appears to be a rising issue.
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Affiliation(s)
- Pablo Cortegoso Valdivia
- University Division of Gastroenterology, Department of Medical Sciences, City of Health and Science University Hospital, Turin, Italy
| | | | - Marco Pennazio
- University Division of Gastroenterology, Department of Medical Sciences, City of Health and Science University Hospital, Via Cavour 31, 10123 Turin, Italy
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Smerdel MP, Skytte AB, Jelsig AM, Ebbehøj E, Stochholm K. Revised Danish guidelines for the cancer surveillance of patients with Cowden Syndrome. Eur J Med Genet 2020; 63:103873. [PMID: 32058060 DOI: 10.1016/j.ejmg.2020.103873] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 11/05/2019] [Accepted: 02/01/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Cowden syndrome is a cancer predisposition syndrome caused by pathogenic variants in PTEN. The affected patients possess an increased risk of breast, thyroid, renal, colorectal, endometrial cancers as well as malignant melanoma. Thus prophylactic surveillance and follow up is crucial for these patients. METHODS A review of the literature including existing guidelines from the years 1996 until 2017 was carried out. In total, 2078 scientific papers were identified through database searches on Cowden syndrome. Among these, 11 manuscripts were included based on scientific relevance and quality. Expert consensus was reached to define management guidelines. RESULTS The literature revealed a high risk of cancer in specific organs for patients diagnosed with Cowden Syndrome. Alternative management guidelines were proposed and discussed. CONCLUSIONS Here we propose a revised set of management guidelines for patients with Cowden syndrome in Denmark to address the increased risk of various cancer types.
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Affiliation(s)
- Maja Patricia Smerdel
- Department of Clinical Genetics, Lillebaelt Hospital - University Hospital of Southern Denmark, Vejle, Denmark.
| | - Anne-Bine Skytte
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
| | - Anne Marie Jelsig
- Clinical Genetic Clinic, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
| | - Eva Ebbehøj
- Department of Internal Medicine and Diabetes, Aarhus University Hospital, Aarhus, Denmark.
| | - Kirstine Stochholm
- Department of Pediatrics, Center of Rare Diseases, Aarhus University Hospital and Department of Internal Medicine and Diabetes, Aarhus University Hospital, Aarhus, Denmark.
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Kastrinos F, Samadder NJ, Burt RW. Use of Family History and Genetic Testing to Determine Risk of Colorectal Cancer. Gastroenterology 2020; 158:389-403. [PMID: 31759928 DOI: 10.1053/j.gastro.2019.11.029] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 11/11/2019] [Accepted: 11/18/2019] [Indexed: 12/20/2022]
Abstract
Approximately 35% of patients with colorectal cancer (CRC) have a family history of the disease attributed to genetic factors, common exposures, or both. Some families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5% to 10% of CRC cases. Most families with a history of CRC and/or adenomas do not carry genetic variants associated with cancer syndromes; this is called common familial CRC. Our understanding of familial predisposition to CRC and cancer syndromes has increased rapidly due to advances in next-generation sequencing technologies. As a result, there has been a shift from genetic testing for specific inherited cancer syndromes based on clinical criteria alone, to simultaneous testing of multiple genes for cancer-associated variants. We summarize current knowledge of common familial CRC, provide an update on syndromes associated with CRC (including the nonpolyposis and polyposis types), and review current recommendations for CRC screening and surveillance. We also provide an approach to genetic evaluation and testing in clinical practice. Determination of CRC risk based on family cancer history and results of genetic testing can provide a personalized approach to cancer screening and prevention, with optimal use of colonoscopy to effectively decrease CRC incidence and mortality.
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Affiliation(s)
- Fay Kastrinos
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York; Division of Digestive and Liver Diseases, Columbia University Irving Medical Center and the Vagelos College of Physicians and Surgeons, New York, New York.
| | - N Jewel Samadder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona
| | - Randall W Burt
- Department of Gastroenterology, University of Utah, Salt Lake City, Utah; Emeritus Professor of Medicine, University of Utah, Salt Lake City, Utah
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Lorca V, Garre P. Current status of the genetic susceptibility in attenuated adenomatous polyposis. World J Gastrointest Oncol 2019; 11:1101-1114. [PMID: 31908716 PMCID: PMC6937445 DOI: 10.4251/wjgo.v11.i12.1101] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 08/18/2019] [Accepted: 10/14/2019] [Indexed: 02/05/2023] Open
Abstract
Adenomatous polyposis (AP) is classified according to cumulative adenoma number in classical AP (CAP) and attenuated AP (AAP). Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and MUTYH. However, the contribution of genetic susceptibility to AAP is lower and less understood. New predisposition genes have been recently proposed, and some of them have been validated, but their scarcity hinders accurate risk estimations and prevalence calculations. AAP is a heterogeneous condition in terms of severity, clinical features and heritability. Therefore, clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes, and the detection rate is low. Elucidation and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family members. This review aims to update the genetic knowledge of AAP, and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.
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Affiliation(s)
- Víctor Lorca
- Laboratorio de Oncología Molecular, Grupo de Investigación Clínica y Traslacional en Oncología, Hospital Clínico San Carlos, Madrid 28040, Spain
| | - Pilar Garre
- Laboratorio de Oncología Molecular, Servicio de Oncología, Hospital Clínico San Carlos, Madrid 28040, Spain
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Singh S, Gupta K, Pendalya SK, Kondreddy K. Genetic Implication and Dental Consideration in Syndromes with Benign and Malignant Oral Neoplastic Component: A Narrative Review. JOURNAL OF ADVANCED ORAL RESEARCH 2019. [DOI: 10.1177/2320206819878358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background and Objective:The presence of an internal and often occult malignancy may be forewarned by various oral manifestations. Several of these findings are preferentially localized to the head and neck region, including the oral cavity. This places the dental practitioner in a unique position to detect these signs and symptoms of occult neoplastic involvement. Because they may be present before an established syndrome or cancer diagnosis, even representing the initial expression of disease in some cases, early recognition by a dentist may lead to timely diagnosis and management of these syndromes. Thus, the aim of this narrative review was literature search and gathering data of such syndromes.Materials and Methods:A Medline–PubMed search was conducted of the literature using the keywords “syndrome,” “dental management,” “Cowden’s syndrome,” “Peutz–Jeghers syndrome,” “malignant component,” “Gardner’s syndrome,” “Gorlin–Goltz syndrome,” and “McCune–Albright syndrome.” The search strategy was limited to human studies (case reports and case series), full-text English articles published from January 1, 2000, to mid-2019. Irrelevant articles or articles with inadequate information were omitted.Results:A total of 36 pieces of literature were reviewed, of which 13 were literature reviews, 15 case reports, 3 expert committee guides and updates, and 4 original research papers, and 1 was a book.Conclusion:These syndromes pose risk during dental practice, which necessitates extra awareness and caution to prevent potential complications. Although, the multidisciplinary approach in treating these cases is not well documented, any related information may be helpful in understanding the pathogenesis and the nature of these syndromes.
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Affiliation(s)
- Saurabh Singh
- Faculty of Dentistry, AIMST University, Bedong, Kedah, Malaysia
| | - Khushboo Gupta
- Faculty of Dentistry, AIMST University, Bedong, Kedah, Malaysia
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Variable Features of Juvenile Polyposis Syndrome With Gastric Involvement Among Patients With a Large Genomic Deletion of BMPR1A. Clin Transl Gastroenterol 2019; 10:e00054. [PMID: 31259752 PMCID: PMC6708668 DOI: 10.14309/ctg.0000000000000054] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Loss-of-function mutations of BMPR1A cause juvenile polyposis syndrome (JPS), but large genomic deletions in BMPR1A are rare, reported in few families only, and data regarding the associated phenotype are limited.
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Kim SW, Kim HC, Oh J, Won KY, Park SJ, Yang DM. Tumors of the jejunum and ileum: a pattern-based imaging approach on CT. Abdom Radiol (NY) 2019; 44:2337-2345. [PMID: 30877330 DOI: 10.1007/s00261-019-01978-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Since a broad spectrum of tumors can occur in the small bowels, it is not easy to make a correct differential diagnosis among small bowel tumors on CT findings. Therefore, once a mass is detected on CT, the radiologist needs to analyze the mass based on presenting patterns such as location, multiplicity, morphology, and enhancement patterns. In this article, we will illustrate various kinds of small bowel tumors based on imaging patterns at CT to facilitate making a correct diagnosis.
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Affiliation(s)
- Sang Won Kim
- Department of Radiology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, 149 Sangil-Dong, Gangdong-Gu, Seoul, 134-727, Korea.
| | - Hyun Cheol Kim
- Department of Radiology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, 149 Sangil-Dong, Gangdong-Gu, Seoul, 134-727, Korea
| | - Jiyoung Oh
- Department of Radiology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, 149 Sangil-Dong, Gangdong-Gu, Seoul, 134-727, Korea
| | - Kyu Yeoun Won
- Deparment of Pathology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Seong Jin Park
- Department of Radiology, Kyung Hee University Hospital, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Dal Mo Yang
- Department of Radiology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, 149 Sangil-Dong, Gangdong-Gu, Seoul, 134-727, Korea
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Pennazio M, Venezia L, Cortegoso Valdivia P, Rondonotti E. Device-assisted enteroscopy: An update on techniques, clinical indications and safety. Dig Liver Dis 2019; 51:934-943. [PMID: 31138509 DOI: 10.1016/j.dld.2019.04.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 02/22/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022]
Abstract
After more than 15 years since its introduction into clinical practice, indications for device-assisted enteroscopy have greatly expanded. Alongside the consolidated indications such as the diagnosis and treatment of small bowel bleeding, Crohn's disease, hereditary polyposis, small-bowel tumors and complicated celiac disease, device-assisted enteroscopy is nowadays largely used to perform endoscopic retrograde cholangiopancreatography in patients with altered anatomy, stent placement, retrieval of foreign bodies, direct insertion of jejunal feeding tubes, and in selected cases of incomplete colonoscopy. This has been made possible by the technical improvements of the enteroscopes and accessories and by the widespread use of the method. Device-assisted enteroscopy endotherapy currently offers a safe and effective alternative to major surgery and often represents the preferred option for treatment of small-bowel pathology. Its safety profile is favourable even in the elderly patient, provided that it is performed in high-volume and experienced centers. The evolution of the enteroscopy technique is a challenge for the future and could be facilitated by the new enteroscopes models. These prototypes need a thorough clinical and safety assessment especially for the complex therapeutic procedures. Large prospective, multicenter studies should be performed to assess whether the use of device-assisted enteroscopy leads to improved patients' long-term outcomes.
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Affiliation(s)
- Marco Pennazio
- University Division of Gastroenterology, Department of Medical Sciences, University of Turin, City of Health and Science, Italy.
| | - Ludovica Venezia
- University Division of Gastroenterology, Department of Medical Sciences, University of Turin, City of Health and Science, Italy
| | - Pablo Cortegoso Valdivia
- University Division of Gastroenterology, Department of Medical Sciences, University of Turin, City of Health and Science, Italy
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