Genetic and phenotypic attributes of splenic marginal zone lymphoma.

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.

Circulating tumor DNA for comprehensive noninvasive monitoring of lymphoma treated with ibrutinib plus nivolumab.

To advance the use of circulating tumor DNA (ctDNA) applications, their broad clinical validity must be tested in different treatment settings, including targeted therapies. Using the prespecified longitudinal systematic collection of plasma samples in the phase 1/2a LYM1002 trial (registered on www.clinicaltrials.gov as NCT02329847), we tested the clinical validity of ctDNA for baseline mutation profiling, residual tumor load quantification, and acquisition of resistance mutations in patients with lymphoma treated with ibrutinib+nivolumab. Inclusion criterion for this ancillary biological study was the availability of blood collected at baseline and cycle 3, day 1. Overall, 172 ctDNA samples from 67 patients were analyzed by the LyV4.0 ctDNA Cancer Personalized Profiling Deep Sequencing Assay. Among baseline variants in ctDNA, only TP53 mutations (detected in 25.4% of patients) were associated with shorter progression-free survival; clones harboring baseline TP53 mutations did not disappear during treatment. Molecular response, defined as a >2-log reduction in ctDNA levels after 2 cycles of therapy (28 days), was achieved in 28.6% of patients with relapsed diffuse large B-cell lymphoma who had ≥1 baseline variant and was associated with best response and improved progression-free survival. Clonal evolution occurred frequently during treatment, and 10.3% new mutations were identified after 2 treatment cycles in nonresponders. PLCG2 was the topmost among genes that acquired new mutations. No patients acquired the C481S BTK mutation implicated in resistance to ibrutinib in CLL. Collectively, our results provide the proof of concept that ctDNA is useful for noninvasive monitoring of lymphoma treated with targeted agents in the clinical trial setting.

Arteria epigástrica inferior: técnica de utilización como injerto libre en revascularización miocárdica / Inferior epigastric artery: technic by using it as free graft in myocardial revascularization

La arteria epigástricz inferior (AEI) ha surgido en el último tiempo como un conducto alternativo en la cirugía de revascularización miocárdica. Sus ventajas anatómicas y funcionales han influido en su uso. Hemos efectuado 27 revascularizaciones coronarias utilizando la AEI. Esta se ha indicado principalmente en pacientes menores de 60 años, para ofrecerles un mayor número de injertos arteriales al asociarlo al uso de la arteria mamaria interna, como también en portadores de várices bilaterales y safenectomizados. Ningún conducto disecado fue desechado. Su largo permite su utilización en cualquier vaso coronario. Un paciente falleció como consecuencia de su mala función ventricular previa. En el seguimiento alejado, el 92.3 por ciento de los pacientes se encuentran asintomáticos. La AEI es un conducto de fácil obtención y en su utilización hemos desarrollado alternativas que conducen a un buen resultado quirúrgico, faltando aún algunos años de seguimiento para determinar su comportamiento alejado

Cardiopatía coronaria y aneurisma aorta abdominal: uso selectivo de cirugía combinada / Combined surgery for abdominal aortic aneurysm and coronary artery disease: case report

La realización en forma combinada de revascularización coronaria y cirugía de aneurisma de aorta abdominal es una alternativa de manejo quirúrgico para un grupo seleccionado de pacientes portadores de ambas patologías que se está empleando cada vez con mayor frecuencia dado los excelentes resultados reportados. Presentamos en esta oportunidad el primer paciente tratado de esta forma en nuestra institución, el cual evolucionó en forma satisfactoria sin presentar complicaciones post operatorias y analizamos sus indicaciones y beneficios. No obstante que nuestra experiencia es limitada, el caso que presentamos y que las series internacionales están constituídas por no más de 12 pacientes, creemos que esta técnica de cirugía combinada se constituirá en el futuro en una alternativa segura para el manejo de muchos pacientes portadores de ambas patologías