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1. Case report: Uncommon gastric metastasis as a presentation of recurrent clear cell renal cell carcinoma

Author

Josep Sabaté-Ortega, Marc Albert-Carrasco, Carmen Escribano-Ferrer, Gerard Grau-Manrubia, Clàudia Fina-Planas, Carme López-Núñez, Eduard Teixidor-Vilà, Elisabet Bujons-Buscarons, Clàudia Montañés-Ferrer, and Núria Sala-González

Subjects
renal cell carcinoma, gastric metastasis, prognostic markers, targeted therapy, pathophysiology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Renal cell carcinoma (RCC) is a kidney neoplasm that accounts for 85% of cases and has complex genetic pathways that affect its development and progression. RCC metastasis can occur in 20%-50% of patients and usually affects distant organs. Gastric metastases (GM) from RCC are rare and present as polyp-like growths in the submucosal layer, accounting for 0.2%-0.7% of cases. This case report describes an 84-year-old female with Furhman grade II ccRCC who presented with an atherothrombotic ischemic stroke and gastrointestinal bleeding nine years post-radical nephrectomy. Gastroscopy revealed a 12mm pseudopedicled gastric lesion with ulceration and bleeding, diagnosed as metastatic ccRCC. The discussion focuses on the rarity, diagnostic challenges, and prognostic elements of gastric metastasis from RCC. The median survival after detecting digestive metastasis varies widely, and the mechanisms include direct invasion and dissemination through lymphatic, transcelomic, or hematogenous routes. Prognostic markers encompass patient history, symptoms, time since RCC diagnosis, overall health, and genetic factors. Surgical removal of gastric lesions and targeted therapy are treatment options that can improve survival. This case report highlights the need for further research to enhance diagnostic and treatment strategies for this rare aspect of RCC pathophysiology.

Published
2024
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2. Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

Author

Javier Fernández-Fernández, Concepción Gimeno, Maria Saumoy, María Eugenia Soria, Pau Gilabert, Gasshan Mereish, Helena Masnou-Ridaura, Federico Sáez-Royuela, Javier Salmerón, Raúl Rodríguez, Imma Ocaña, Juan Buenestado, José Francisco Macías-Sánchez, Xavier Forns, Elisabet Deig, Silvia Montoliu, José Castellote, Maria Isabel Costafreda, Ramiro Macenlle, Ildefonso Quiñones, David Tabernero, Jordi Niubó, Silvia Fábregas, Xavier Pamplona, Qian Chen, Maria Carlota Londoño, Juan Turnes, Mercè Barenys, Javier García-Samaniego, Agustín Albillos, Javier Crespo, Juan Manuel Pascasio, Joana Villaverde, B. Sacristan, Silvia Sauleda, Mar Riveiro-Barciela, Judit Carbonell, Silvia Salord, Oscar del Río, Leticia González-Moreno, Doroteo Acero-Fernández, Martín Prieto, A. Estebanez, Manolo Romero-Gómez, Arkaitz Imaz, Xavier Torras, María José López-de-Goicoechea, Jordi Navarro, Manuel Delgado-Blanco, Rosa Maria Morillas, Yolanda Real, Gemma Olivé, Rosa M Lopez, Salvador Augustin, Joan Carles Quer, Angels García-Flores, Nuria Margall, Leonardo Nieto-Aponte, Ángeles Castro-Iglesias, Ariadna Rando-Segura, Verónica Saludes, Rosa Durández, Elena Vargas-Accarino, Mireia Cairó, María Luisa García-Buey, Carme Mora-Moruny, Álvaro Mena-de-Cea, Paloma Sanz-Cameno, Lluis Castells, Miguel Miralbés, Francisco Suárez, Rosa Roca, Joaquín Cabezas, Carlos González-Portela, Albert Bernet, Pilar Castillo-Grau, Juan García-Costa, Mercedes Guerrero-Murillo, R. Quiles, Martin Bonacci, Juan Arenas, Juan Ignacio Esteban, Xavier Xiol, Silvia Viroles, Antonio Madejón, Sabela Lens, Maria Buti, María Silvan di Yacovo, Francisco Rodriguez-Frias, Manuel Rodríguez, Damir Garcia-Cehic, Esteban Domingo, Alejandra Otero, Elisa Martró, Manuel Hernández-Guerra, Inmaculada Fernández, Alba Cachero, Pilar Vázquez-Rodríguez, Carmen García-Martin, José A. Carrión, Miguel Angel Simón, Soledad López-Calvo, Gloria Sánchez-Antolín, Fernando Lázaro, J. Llaneras, Montserrat Forné, Meritxell Llorens-Revull, Maria Juana Gomez-Alonso, Francisco José Martínez-Cerezo, Isabel Conde, Maria Francesca Cortese, Silvia Blanch, Blau Camps, David Vieito, Sofía P. Ruzo, Moisés Diago, Marta Vila, Matilde Trigo-Daporta, Mercè Rosinach, Irati Fernandez-Alonso, Carme López-Núñez, María José Ferri, Georg von Massow, Jose Luis Calleja, Rafael Esteban, Sofía Pérez-del-Pulgar, Rafael Medina, Carme Baliellas, Ángeles Vázquez, Josep Quer, Mercè Roget, Angel Rubín, Celia Perales, Jose Antonio delCampo, María Dolores Ocete, T. Casanovas, J.J. Sanchez-Ruano, Lluís Force, A Martín-Cardona, R.J. Andrade, Angelina Cañizares, Víctor Vargas-Blasco, Marta Bes, Zoe Mariño, Josep Gregori, and Raquel Baluja-Pino

Subjects
0301 basic medicine, Genotype, Hepatitis C virus, 030106 microbiology, Failure, Hepacivirus, medicine.disease_cause, Direct-acting antivirals, Antiviral Agents, Deep sequencing, Antiviral treatment, Direct-acting antivirals, Failure, HCV, NGS, RAS, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Drug Resistance, Multiple, Viral, Interferon, Virology, Medicine, Humans, Treatment Failure, NS5A, NS5B, Pharmacology, business.industry, Ribavirin, High-Throughput Nucleotide Sequencing, Hepatitis C, Subtyping, 030104 developmental biology, chemistry, Antiviral treatment, Spain, NGS, HCV, Mutation, Drug Therapy, Combination, business, medicine.drug, RAS
Abstract

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

Published
2020

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