Differentially Expressed Genes Involved in Primary Resistance to Immunotherapy in Patients with Advanced-Stage Pulmonary Cancer.

In the last few years, nivolumab has become the standard of care for advanced-stage lung cancer patients. Unfortunately, up to 60% of patients do not respond to this treatment. In our study, we identified variations in gene expression related to primary resistance to immunotherapy. Bronchoscopy biopsies were obtained from advanced non-small cell lung cancer (NSCLC) patients previously characterized as responders or non-responders after nivolumab treatment. Ten tumor biopsies (from three responders and seven non-responders) were analyzed by the differential expression of 760 genes using the NanoString nCounter platform. These genes are known to be involved in the response to anti-PD1/PD-L1 therapy. All the patients were treated with nivolumab. Examining the dysregulated expression of 24 genes made it possible to predict the response to nivolumab treatment. Supervised analysis of the gene expression profile (GEP) revealed that responder patients had significantly higher levels of expression of CXCL11, NT5E, KLRK1, CD3G, GZMA, IDO1, LCK, CXCL9, GNLY, ITGAL, HLA-DRB1, CXCR6, IFNG, CD8A, ITK, B2M, HLA-B, and HLA-A than did non-responder patients. In contrast, PNOC, CD19, TP73, ARG1, FCRL2, and PTGER1 genes had significantly lower expression levels than non-responder patients. These findings were validated as predictive biomarkers in an independent series of 201 patients treated with nivolumab (22 hepatocellular carcinomas, 14 non-squamous cell lung carcinomas, 5 head and neck squamous cell carcinomas, 1 ureter/renal pelvis carcinoma, 120 melanomas, 4 bladder carcinomas, 31 renal cell carcinomas, and 4 squamous cell lung carcinomas). ROC curve analysis showed that the expression levels of ITK, NT5E, ITGAL, and CD8A were the best predictors of response to nivolumab. Further, 13/24 genes showed an adverse impact on overall survival (OS) in an independent, large series of patients with NSCLC (2166 cases). In summary, we found a strong association between the global GEP of advanced NSCLC and the response to nivolumab. The classification of NSCLC patients based on GEP enabled us to identify those patients who genuinely benefited from treatment with immune checkpoint inhibitors (ICIs). We also demonstrated that abnormal expression of most of the markers comprising the genomic signature has an adverse influence on OS, making them significant markers for therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these biomarkers.

Intravascular schwannoma as an extremely unusual cause of vein obstruction: a case report.

The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In this report, we present a case of a 68-year-old woman who had a soft tissue nodule at the posterior calf of her left leg during a physical examination. Pathological examination was performed after complete surgical excision. The patient underwent follow-up for 12 months after surgery without evidence of recurrence or any other complication. This is the first case of intravascular schwannoma reported as a cause of vein obstruction. Microscopically, the tumor was composed of Schwann spindle cells that were immunoreactive for S100 protein and SOX10. This tumor was surrounded by a well-defined vascular smooth muscle wall. Prospective series are required to improve the knowledge on the underlying mechanisms of intravascular schwannoma development.

Desarrollo y resultados de un nuevo programa de trasplante de páncreas en España: la visión del cirujano / Development and results of a novel pancreas transplant program in Spain: the surgeon's point of view

INTRODUCCIÓN: El trasplante simultáneo de páncreas-riñón se encuentra indicado para pacientes con diabetes tipo 1 y enfermedad renal terminal. Los resultados son excelentes aunque el número de procedimientos parece ser un factor que afecta a la supervivencia de paciente e injerto estando en relación con la morbilidad quirúrgica, derivada de complicaciones pancreáticas. el objetivo del estudio es describir el desarrollo de un nuevo programa y exponer los resultados en un centro con un volumen bajo de trasplantes. MÉTODOS: Analizamos 53 trasplantes simultáneos de páncreas-riñón, en un período de 7 años (2009-2016), con una mediana de seguimiento de 39 meses. RESULTADOS: Dos pacientes han fallecido, uno tras parada cardíaca en postoperatorio y otro tras accidente de tráfico complicado con una neumonía. Entre los 51 pacientes vivos se han perdido 2 injertos, uno por un rechazo crónico tras cuatro años del trasplante y otro por trombosis arterial a los 20 días del mismo, motivo, este último, de la única trasplantectomía realizada. En diez pacientes se han realizado una o más reintervenciones: pancreatitis (n=3), oclusión intestinal (n=4), trombosis arterial (n=1), fístula con peritonitis (n=1) y hemoperitoneo (n=1). La supervivencia del paciente y del injerto a 1, 3, y 5 años fue del 98, 95 y 95% y del 96, 93 y 89%, respectivamente. Conclusiones Los resultados muestran que un nuevo programa de trasplante pancreático puede conseguir resultados similares a los de grupos con mayor volumen y experiencia. Una adecuada selección de donantes y receptores, una técnica homogénea y el aprendizaje con grupos expertos garantizan estos resultados

INTRODUCTION: Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS: We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months). RESULTS: Out of the total of this series, two patients died: one patient because of cardiac arrest immediately after surgery; and another patient due to traffic accident, complicated by pneumonia. Among the 51 living patients, two grafts were lost: one due to chronic rejection four years after transplantation; and the other due to arterial thrombosis 20 days after transplantation (the only case requiring transplantectomy). In ten patients, one or more re-operations were necessary due to the following: graft pancreatitis (n=4), small intestinal obstruction (n=4), arterial thrombosis (n=1), fistula (n=1) and hemoperitoneum (n=1). Overall patient and graft survival rates after 1, 3 and 5 years were 98, 95 and 95% and 96, 93 and 89%, respectively. CONCLUSIONS: This study has shown that the results of a new pancreas transplant program, which relies on the previous experience of other groups, do not demonstrate a learning curve. Adequate surgeon education and training, as well as the proper use of standardized techniques, should ensure optimal results

Alteraciones genéticas del cáncer colorrectal: implicaciones en el pronóstico y en el tratamiento de la enfermedad / No disponible

En los últimos años se ha avanzado de forma notable en el conocimiento de las distintas alteraciones genéticas presentes en el cáncer colorrectal (CCR) y su asociación con la ontogenia y la progresión tumoral. Así, mientras que la presencia de mutaciones en los genes APC y KRAS, se asocia con el proceso de transformación neoplásica, las mutaciones en SMAD y DCC alteraciones a nivel de los cromosomas 7, 17p y 18q y los cariotipos complejos constituirían habitualmente alteraciones genéticas asociadas con la progresión tumoral. Desde el punto de vista pronóstico, la presencia de inestabilidad de microsatélites (IMS) se asocia con menores tasas de recaída y mayor supervivencia global, así como con la resistencia a tratamiento adyuvante con fluoropirimidinas, mientras que las mutaciones en el gen BRAF se han asociado con recaídas precoces. A nivel molecular, los estudios sobre la heterogeneidad genética intratumoral asociada al proceso metastásico del CCR se han centrado en analizar mutaciones de genes involucrados en el tratamiento de la enfermedad, observándose la existencia de distintos perfiles mutacionales entre tumores primarios, metástasis ganglionares y metástasis hepáticas de un mismo paciente. En este sentido, la heterogeneidad genética del CCR a nivel intratumoral podría explicar las altas tasas de recaída y los tumores refractarios tratados con anticuerpos monoclonales

No disponible

Estrategias para el diagnóstico y seguimiento molecular de leucemias y linfomas / Different tools for the diagnosis and molecular follow-up of leukemias and lymphomas

No disponible

Alteraciones citogenéticas en meningiomas y su impacto en la evolución de la enfermedad / Cytogenetic alterations in meningioma tumors and their impact on disease outcome

En los últimos años se ha avanzado de forma notable en el conocimiento de las alteraciones genéticas presentes en los meningiomas y su asociación con la ontogenia y progresión tumoral. Así, mientras que la presencia de monosomía 22/22q­, asociada a mutación en los genes NF2, BAM22, RRP22, GAR22, MN1, SMARCB1, CLH22 y LARGE, se asocia con el proceso de transformación neoplásica, la monosomía 14, deleciones 1p, alteraciones en los cromosomas 9p, 10q y 17q y los cariotipos complejos constituirían habitualmente alteraciones genéticas asociadas con la progresión tumoral. Desde el punto de vista pronóstico, la información disponible sobre el valor de las anomalías genéticas sigue siendo escasa; no obstante, la presencia de ganancias del cromosoma 22 en el contexto de un cariotipo complejo, así como la deleción del cromosoma 1p y la monosomía 14, se ha asociado con una supervivencia libre de recaída significativamente más corta, y esta última alteración ha mostrado un valor pronóstico independiente

In recent years important advances have been achieved in the understanding of the genetic abnormalities present in meningioma tumors and its association with the ontogeny and progression of these tumor. Accordingly, while the presence of monosomy 22/22q­, associated with mutation of the NF2, BAM22, RRP22, GAR22, MN1, SMARCB1, CLH22 and/or LARGE genes, is associated with neoplasic transformation, other alterations such us monosomy 14, del(1p), different chromosomal abnormalities localized at 9p, 10q and 17q and complex karyotypes are frequently related to tumor progression. From the clinical point of view, currently available information about the impact of the different cytogenetic abnormalities on disease behavior and patient outcome is still scanty; nevertheless, the presence of gains of chromosome 22 in the context of a hyperdiploid karyotype, as well as del(1p) and monosomy 14 have been associated with a statistically significantly shorter recurrence-free survival, this later abnormality showing an independent prognostic value