Article
Oncology
Geoffrey Roberts, Patrick R. Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L. Davis, Sam Grimes, Theresa A. Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P. Stanich, Vivian E. Strong, Pardeep Kaurah
Summary: The study aims to define the standard of care for follow-up after prophylactic total gastrectomy (PTG) through a combination of literature review and two-round Delphi consensus. The guidelines provide a framework to best manage people following PTG, although the evidence supporting them is limited. They could also support the collection of information on the long-term effects of PTG.
Article
Oncology
Joseph D. Forrester, Deshka Foster, James M. Ford, Teri A. Longacre, Uri Ladabaum, Sara Fry, Jeffrey A. Norton
Summary: This study reports the long-term outcomes of total gastrectomy for patients with a family history of gastric cancer and CDH1 gene mutations that predispose to hereditary diffuse gastric cancer (HDGC). The results show that total gastrectomy is recommended for patients with inherited CDH1 mutations and the long-term quality of life following the surgery is acceptable.
Review
Biochemistry & Molecular Biology
Lidia-Sabina Cosma, Sophie Schlosser, Hauke C. Tews, Martina Mueller, Arne Kandulski
Summary: This article presents an overview of the genetic characteristics and current treatment approaches of hereditary diffuse gastric cancer (HDGC). It highlights the importance of the CTNNA1 gene, among others, in relation to this disease, and emphasizes the need for risk management in diagnosing patients through genetic testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Bilal Asif, Amber Leila Sarvestani, Lauren A. Gamble, Sarah G. Samaranayake, Amber L. Famiglietti, Grace -Ann Fasaye, Martha Quezado, Markku Miettinen, Louis Korman, Christopher Koh, Theo Heller, Jeremy L. Davis
Summary: This study aimed to evaluate the safety and effectiveness of endoscopy in individuals with CDH1 variants, particularly in those who declined prophylactic total gastrectomy. The study found that endoscopy had a certain level of safety and effectiveness in early detection and interception of gastric cancer.
Article
Obstetrics & Gynecology
Jun Xiao, Hui Li, Fenggui Xue, Zhifei Luo, Yanyang Pang
Summary: This case report describes the prenatal diagnosis of a fetus with choroid plexus cyst detected during fetal development. Genetic counseling and sequencing revealed a pathogenic CDH1 deletion in the fetus, with affected family members also having the same genetic mutation. After genetic counseling by hospital geneticists, the couple decided to terminate the pregnancy.
BMC PREGNANCY AND CHILDBIRTH
(2023)
Article
Gastroenterology & Hepatology
Lyvianne Decourtye-Espiard, Parry Guilford
Summary: Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by a high incidence of diffuse gastric cancer (DGC) and lobular breast cancer (LBC). It is caused by germline mutations in the CDH1 and CTNNA1 genes. This article discusses the genetics, clinical phenotype, pathology, tumor initiation mechanism, natural history, and clinical management of HDGC.
Article
Gastroenterology & Hepatology
Monika Laszkowska, Laura Tang, Elvira Vos, Stephanie King, Erin Salo-Mullen, Patrick T. Magahis, Miseker Abate, Amanda Catchings, Ann G. Zauber, Anne I. Hahn, Mark Schattner, Daniel Coit, Zsofia K. Stadler, Vivian E. Strong, Arnold J. Markowitz
Summary: This study aimed to identify endoscopic findings and biopsy practices associated with the detection of signet ring cell carcinoma (SRCC) in individuals with germline pathogenic CDH1 variants. The results showed that targeted biopsy sampling of gastric pale mucosal areas and increasing the number of biopsy samples taken can improve the detection of SRCC. The findings support updated endoscopic surveillance guidelines and further studies are needed to refine endoscopic protocols for detecting SRCC in this high-risk population.
GASTROINTESTINAL ENDOSCOPY
(2023)
Review
Health Care Sciences & Services
Christo Kole, Nikolaos Charalampakis, Stratigoula Sakellariou, George Papaxoinis, Konstantinos G. Apostolou, Nikolaos Machairas, Ioannis S. Papanikolaou, Dimitrios Schizas
Summary: Gastric cancer is a common malignancy, with the majority being sporadic and only a small percentage being hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare early-onset disease primarily caused by genetic alterations in the E-cadherin gene and beta-catenin gene. This study provides an overview of the molecular basis of HDGC, outlines essential elements of genetic counseling and surveillance, and offers a practical summary of current guidelines for the clinical management and treatment of high-risk individuals and patients with early-stage disease.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
Chihiro Matsumoto, Masaaki Iwatsuki, Shiro Iwagami, Takeshi Morinaga, Kohei Yamashita, Kenichi Nakamura, Kojiro Eto, Junji Kurashige, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Yoshihiro Komohara, Hideo Baba
Summary: A 41-year-old woman was admitted to the hospital for epigastralgia and was diagnosed with gastric adenocarcinoma with multiple liver metastases. Her genetic testing revealed a point mutation in the APC gene. Two older brothers and their mother also had the same genomic mutation and were diagnosed with GAPPS, undergoing prophylactic surgery.
Article
Surgery
Mary K. Bryant, Rachel Sillcox, William M. Grady, Brant K. Oelschlager
Summary: Background: CDH1 gene mutations are the main cause of hereditary diffuse gastric cancer. Prophylactic total gastrectomy (PTG) is recommended for CDH1 carriers. This study analyzed laparoscopic PTG with D1 lymphadenectomy for CDH1 mutation patients, showing acceptable surgical and oncologic outcomes.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Article
Endocrinology & Metabolism
Lauren A. Gamble, Rachael Lopez, Suraj Rajasimhan, Sarah G. Samaranayake, Cassidy Bowden, Amber L. Famiglietti, Andrew M. Blakely, Smita Jha, Mark A. Ahlman, Jeremy L. Davis
Summary: Patients with CDH1 germline variants undergoing prophylactic TG are at risk of bone mineral density loss and micronutrient deficiencies. Serum biomarkers of mineral metabolism did not change significantly, but average BMD was decreased at 12 months post-TG. Adherence to calcium and multivitamin supplementation is associated with the preservation of BMD.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Oncology
Katherine Dixon, Tom Brew, David Farnell, Tanis D. Godwin, Simon Cheung, Christine Chow, Monica Ta, Germain Ho, Minh Bui, J. Maxwell Douglas, Kieran R. Campbell, Amal El-Naggar, Pardeep Kaurah, Steve E. Kalloger, Howard J. Lim, David F. Schaeffer, Dawn Cochrane, Parry Guilford, David G. Huntsman
Summary: Hereditary diffuse gastric cancer (HDGC) is caused by germline variants in the CDH1 gene, but the mechanisms underlying its initiation are unclear. The study found that deregulation of developmental transcriptional programs may precede malignancy in HDGC.
JOURNAL OF PATHOLOGY
(2021)
Article
Surgery
Adrienne B. Shannon, Richard J. Straker, Douglas L. Fraker, Robert E. Roses, John T. Miura, Giorgos C. Karakousis
Summary: The research analyzed the short-term mortality of patients undergoing total gastrectomy for stage I to III gastric adenocarcinoma, revealing a higher 90-day mortality rate than 30-day mortality rate. Factors such as age, income, disease severity, and treatment facility were associated with the 90-day mortality rate; and the 90-day mortality rate decreased from 14.3% in 2004 to 7.9% in 2015, indicating some improvement.
Article
Oncology
Sang Soo Eom, Sin Hye Park, Bang Wool Eom, Hong Man Yoon, Young-Woo Kim, Keun Won Ryu
Summary: This study aimed to compare the outcomes of laparoscopic total gastrectomy (LTG) with open total gastrectomy (OTG). There was no significant difference in short-term outcomes between the two groups, and the 3-year disease-free survival and 5-year overall survival rates were also similar. Thus, LTG could be an alternative to OTG.
Review
Oncology
Giovanni Corso, Francesca Magnoni, Vincenzo Nicastro, Vincenzo Bagnardi, Cristina Maria Trovato, Paolo Veronesi
Summary: Individuals with germline E-cadherin mutations have a high risk of developing diffuse gastric cancer. Prophylactic total gastrectomy is the only life-saving treatment. Studies show that 85.4% of individuals have gastric cancer detected after PTG, with a higher rate of no cancer identified in the US (19.6%). PTG remains the best treatment for individuals with CDH1 mutations.
SEMINARS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ana M. Moreira, Rui M. Ferreira, Patricia Carneiro, Joana Figueiredo, Hugo Osorio, Jose Barbosa, John Preto, Perpetua Pinto-do-O, Fatima Carneiro, Raquel Seruca
Summary: The extracellular matrix (ECM) plays a crucial role in the development and progression of gastric cancer. Through proteomic analysis, we identified a common ECM signature in gastric cancer and normal mucosa, and found that remodeling of gastric ECM promotes tumor progression. Additionally, we identified COL10A1 and other differentially expressed ECM proteins as important biomarkers in gastric cancer, with some ECM proteins correlating with patient prognosis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Pathology
Naziheh Assarzadegan, Jiayun M. Fang, Lysandra Voltaggio, Robert H. Riddell, Elizabeth A. Montgomery, Oliver G. McDonald, Ryan Coates, Fatima Carneiro, Gregory Y. Lauwers, Michal Kamionek, Laura W. Lamps, Maria Westerhoff
Summary: This study describes the clinicopathologic features of eight patients with syphilitic gastritis, including demographics, clinical presentations, endoscopic findings, and histopathology. All patients exhibited an active chronic gastritis pattern with lymphohistiocytic infiltrates, and some patients showed prominent lymphoid aggregates. The diagnosis was confirmed by immunostaining or direct immunofluorescence staining and PCR. Symptoms resolved after antibiotic therapy in patients with follow-up data.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Genetics & Heredity
Anne-Sophie Denomme-Pichon, Leslie Matalonga, Elke de Boer, Adam Jackson, Elisa Benetti, Siddharth Banka, Ange-Line Bruel, Andrea Ciolfi, Jill Clayton-Smith, Bruno Dallapiccola, Yannis Duffourd, Kornelia Ellwanger, Chiara Fallerini, Christian Gilissen, Holm Graessner, Tobias B. Haack, Marketa Havlovicova, Alexander Hoischen, Nolwenn Jean-Marcais, Tjitske Kleefstra, Estrella Lopez-Martin, Milan Macek, Maria Antonietta Mencarelli, Sebastien Moutton, Rolph Pfundt, Simone Pizzi, Manuel Posada, Francesca Clementina Radio, Alessandra Renieri, Caroline Rooryck, Lukas Ryba, Hana Safraou, Martin Schwarz, Marco Tartaglia, Christel Thauvin-Robinet, Julien Thevenon, Frederic Tran Mau-Them, Aurelien Trimouille, Pavel Votypka, Bert B. A. de Vries, Marjolein H. Willemsen, Birte Zurek, Alain Verloes, Christophe Philippe, Antonio Vitobello, Lisenka E. L. M. Vissers, Laurence Faivre
Summary: Within the Solve-RD project, the European Reference Network aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. The results of the ClinVar low-hanging fruit reanalysis, reasons for previous analysis failure, and lessons learned are presented.
GENETICS IN MEDICINE
(2023)
Article
Oncology
Jose Garcia-Pelaez, Rita Barbosa-Matos, Silvana Lobo, Alexandre Dias, Luzia Garrido, Sergio Castedo, Sonia Sousa, Hugo Pinheiro, Liliana Sousa, Rita Monteiro, Joaquin J. Maqueda, Susana Fernandes, Fatima Carneiro, Nadia Pinto, Carolina Lemos, Carla Pinto, Manuel R. Teixeira, Stefan Aretz, Svetlana Bajalica-Lagercrantz, Judith Balmana, Ana Blatnik, Patrick R. Benusiglio, Maud Blanluet, Vincent Bours, Hilde Brems, Joan Brunet, Daniele Calistri, Gabriel Capella, Sergio Carrera, Chrystelle Colas, Karin Dahan, Robin de Putter, Camille Desseignes, Elena Dominguez-Garrido, Conceicao Egas, D. Gareth Evans, Damien Feret, Eleanor Fewings, Rebecca C. Fitzgerald, Florence Coulet, Maria Garcia-Barcina, Maurizio Genuardi, Lisa Golmard, Karl Hackmann, Helen Hanson, Elke Holinski-Feder, Robert Huneburg, Mateja Krajc, Kristina Lagerstedt-Robinson, Conxi Lazaro, Marjolijn J. L. Ligtenberg, Cristina Martinez-Bouzas, Sonia Merino, Genevieve Michils, Srdjan Novakovic, Ana Patino-Garcia, Guglielmina Nadia Ranzani, Evelin Schrock, Ines Silva, Catarina Silveira, Jose L. Soto, Isabel Spier, Verena Steinke-Lange, Gianluca Tedaldi, Maria-Isabel Tejada, Emma R. Woodward, Marc Tischkowitz, Nicoline Hoogerbrugge, Carla Oliveira
Summary: This study analyzed families carrying rare CDH1 variants, comparing the cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV) or missense variants of unknown significance, and evaluated the performance of expanded criteria for CDH1 testing. The results showed that PV/LPV carriers were positively associated with lobular breast cancer, diffuse gastric cancer, and gastric cancer, while missense variants of unknown significance did not show this positive association.
Article
Oncology
Catarina Neto do Nascimento, Luis Mascarenhas-Lemos, Joao Ricardo Silva, Diogo Sousa Marques, Catarina Ferreira Gouveia, Ana Faria, Sonia Velho, Rita Garrido, Rui Maio, Andreia Costa, Patricia Pontes, Xiaogang Wen, Irene Gullo, Marilia Cravo, Fatima Carneiro
Summary: Gastric cancer is characterized by high morphologic and molecular heterogeneity. The impact of microsatellite instability (MSI) and Epstein-Barr virus (EBV) status in gastric cancer (GC) regarding response to perioperative chemotherapy (POPChT), overall survival (OS), and progression-free survival (PFS) was investigated. Although MSI and EBV status did not influence OS or PFS, females with MSI-high tumors treated with POPChT demonstrated superior survival compared to females with MSS tumors, suggesting that sex disparities and molecular classification may influence treatment options in GC.
Letter
Gastroenterology & Hepatology
M. Blanca Piazuelo, Fatima Carneiro, M. Constanza Camargo
Article
Oncology
Michael Baumann, Julio Celis, Ulrik Ringborg, Manuel Heitor, Anton Berns, Tit Albreht, Jeliazko Arabadjiev, Michael Boutros, Mario Brandenburg, Helena Canhao, Fatima Carneiro, Christine Chomienne, Francesco De Lorenzo, Alexander M. M. Eggermont, Angel Font, Elena Garralda, Margarida Goulart, Rui Henrique, Mark Lawler, Lena Maier-Hein, Francoise Meunier, Simon Oberst, Pedro Oliveira, Maria Papatriantafyllou, Joachim Schuez, Eric Solary, Alfonso Valencia, Rosalia Vargas, Elisabete Weiderpass, Nils Wilking
Summary: European cancer research stakeholders gathered in Heidelberg, Germany, for the 5(th) Gago conference on European Cancer Policy in October 2022. The meeting focused on the current state of cancer research and care policy in Europe, identifying gaps in existing programs and proposing priorities for the future through the Heidelberg Manifesto for cancer research. The discussions in the meeting covered various aspects of cancer research, including infrastructure, digitalization, and collaboration, with an emphasis on implementation and sustainability.
MOLECULAR ONCOLOGY
(2023)
Article
Biology
Celina Sao Jose, Carla Pereira, Marta Ferreira, Ana Andre, Hugo Osorio, Irene Gullo, Fatima Carneiro, Carla Oliveira
Summary: The cell architecture and adhesion between similar cells are maintained by cadherins. E-cadherin, encoded by CDH1 gene, plays a vital role in normal epithelia, while P-cadherin, encoded by CDH3 gene, is mainly present in tumors. The switch from E-cadherin to P-cadherin is common in several epithelial tumors, including gastric cancers. In this study, we revealed a mechanism for the E-cadherin to P-cadherin switch and found it to be associated with increased cell migration and proliferation in gastric cancers.
Article
Cell Biology
Diogo Sousa Marques, Irene Gullo, Luis Mascarenhas-Lemos, Joao Ricardo Silva, Catarina Neto do Nascimento, Patricia Pontes, Lidia Pinho, Luis Cirnes, Xiaogang Wen, Marilia Cravo, Fatima Carneiro
Summary: Microsatellite instability (MSI) is a significant prognostic marker for gastric cancer (GC). Immunohistochemistry (IHC) and polymerase chain reaction (PCR) are used to detect MSI status. The Idylla MSI assay has not been validated for GC but may be a valid alternative.
Review
Oncology
Mariagiulia Dal Cero, Maria Bencivenga, Drolaiz H. W. Liu, Michele Sacco, Mariella Alloggio, Kelly G. P. Kerckhoffs, Federica Filippini, Luca Saragoni, Mar Iglesias, Anna Tomezzoli, Fatima Carneiro, Heike I. Grabsch, Giuseppe Verlato, Lorena Torroni, Guillaume Piessen, Manuel Pera, Giovanni de Manzoni
Summary: The clinical behavior of signet ring cell histology in gastric cancer has been controversial due to the lack of a standardized definition. This meta-analysis aimed to gain a deeper understanding of the prognosis and clinicopathological features of signet ring cell gastric cancer compared to other histologies. The findings revealed that the prognosis of signet ring cell gastric cancer is closely linked to the disease stage and the specific comparison group employed. The lack of standardized classification may contribute to the variability in clinical behavior. Therefore, efforts should be made to establish a uniform classification system for gastric cancer to enhance clarity and coherence in research and clinical practice.
Article
Gastroenterology & Hepatology
Emanuel Dias, Helder Cardoso, Margarida Marques, Rodrigo Liberal, Susana Lopes, Pedro Pereira, Joao Santos-Antunes, Jorge Pinheiro, Joanne Lopes, Fatima Carneiro, Guilherme Macedo
Summary: This study retrospectively analyzed the prevalence, clinical characteristics, and prognostic impact of hepatic amyloidosis among patients undergoing liver biopsy from January 2010 to December 2019. Out of 1,773 liver biopsy procedures, seven cases of hepatic amyloidosis were identified (0.4%), with a higher occurrence in females and a median age of diagnosis of 62 years. The most common clinical manifestations included hepatomegaly, jaundice, and peripheral edema, with some patients being asymptomatic. Abnormal liver biochemical tests, particularly cholestasis, were observed in all patients. Concurrent involvement of other organs, such as nephrotic syndrome and infiltrative cardiomyopathy, was also identified. The one-year mortality rate was 43% and the median survival was 24 months. In conclusion, although rare, hepatic amyloidosis has a poor prognosis, highlighting the importance of early diagnosis.
REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS
(2023)
Article
Genetics & Heredity
Burcu Yaldiz, Erdi Kucuk, Juliet Hampstead, Tom Hofste, Rolph Pfundt, Jordi Corominas Galbany, Tuula Rinne, Helger G. Yntema, Alexander Hoischen, Marcel Nelen, Christian Gilissen, Solve-RD consortium
Summary: This study compared different enrichment kits and sequencing techniques in terms of their ability to cover the entire exome. The results showed that Twist exome capture had significantly better coverage and uniformity across coding regions compared to other kits. Twist performed equally well as short-read and long-read whole genome sequencing, and even at lower average coverage, there was only minimal loss in sensitivity for SNV and CNV detection.
Letter
Gastroenterology & Hepatology
Emanuel Dias, Joao Santos-Antunes, Raquel Portugal, Jorge Pinheir, Fatima Carneiro, Guilherme Macedo
REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS
(2023)
Article
Gastroenterology & Hepatology
Emanuel Dias, Patricia Andrade, Susana Lopes, Raquel Goncalves, Pedro Cardoso, Rui Gaspar, Helder Cardoso, Joanne Lopes, Fatima Carneiro, Guilherme Macedo
Summary: This study aimed to characterize the spectrum of hepatobiliary disorders in patients with inflammatory bowel disease (IBD) who underwent liver biopsy. The results showed that abnormal liver function in IBD patients had various etiologies, and liver biopsy was essential for accurate diagnosis. Nonalcoholic fatty liver disease (NAFLD), drug-induced liver disease (DILI), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC) were the most common diagnoses.
ANNALS OF GASTROENTEROLOGY
(2023)
Article
Endocrinology & Metabolism
Sofia Macedo, Ana Pestana, Liliana Santos, Celestino Neves, Susana Guimaraes, Amaro Duarte-Neto, Marisa Dolhnikoff, Paulo Saldiva, Georgina Alves, Rute Oliveira, Didier Cabanes, Fatima Carneiro, Manuel Sobrinho-Simoes, Paula Soares
Summary: This study found that thyroid cells can be directly infected by the SARS-CoV-2 virus, but there is no clear correlation between the presence of viral genome and the expression of host factors for virus entry.
EUROPEAN THYROID JOURNAL
(2022)