Valoración radiológica del pie zambo congénito idiopático y su correlación clínica en la operación de Codivilla

Thirty-seven patients (52 idiopathic clubfeet) were treated with Codivilla's technique between 1971 and 1985. Radiological measurements and clinical evaluation before and after surgery were performed; a correlation was carried out between these evaluations and personal satisfaction. The results were rated as follows: poor in 4 feet (7.7%), fair in 18 feet (34.6%), good in 24 feet (46.2%) and excellent in 6 feet (11.5%) with a total percentage of satisfactory results amounting to 57.7%. Our conclusion is that when the indications are properly established, Codivilla's technique is a good procedure to correct clubfoot

Tratamiento quirúrgico de las metástasis vertebrales

Las metástasis vertebrales causan dolor y déficit neurológico por la destrucción ósea y compresión medular. Las nuevas terapias oncológicas han prolongado la vida sobrevida de muchos pacientes afectos de tumores de distinto origen y el tratamiento de las metástasis es frecuentemente necesario para mejorar la calidad de vida. Se estudian 121 pacientes afectos de metástasis vertebrales de una variada etiología de tumores primarios, tratados quirúrgicamente entre 1982 y 1995; se utilizaron distintos abordajes e instrumentación según lo requiriera el caso, dependiendo de la localización y expectativa de vida; en ellos se analizaron aspectos como localización del tumor primario, dolor y afectación neurológica pre y post quirúrgicos, complicaciones y evolución. La estabilización quirúrgica junto a la descompresión de las metástasis vertebrales proporciona excelentes resultados en cuanto al alivio del dolor y recuperación del déficit en estos pacientes, mejorando la calidad de sobrevida y apoyando el tratamiento de la enfermedad tumora

Sinostosis congénitas del tarso: concepto, clasificación, diagnóstico y planteamiento terapéutico

incidencia de las sinostosis congénitas del tarso se estima en torno al 1% de la población, siendo una de las causas más comunes de pie plano rígido doloroso en la población pediátrica. La barra calcáneoescafoidea (50%) y el puente astragalocalcá¬neo (40%) son las formas de presentación más frecuentes. La restricción de la movilidad, el dolor mecánico en el lugar de la fusión y la deformidad del calzado referida en la anamnesis deben hacernos sospechar esta entidad. En la exploración física destaca la rigidez del retropié con limitación dolorosa característica de la pronosupinación que ha motivado clásicamente la errónea denominación de pie plano peroneo espástico. El diagnóstico radiológico se hace normalmente con radiografías simples (proyecciones laterales y oblicuas entre 35 y 45º), en las que observamos el osteofito anterior de la cabeza del astrágalo o la imagen de condensación en "media luna" del astrágalo superpuesto con el calcáneo, siendo necesario en ocasiones recurrir al TAC. Entre las posibilidades terapéuticas, el tratamiento quirúr¬gico es el único resolutivo del problema de base. La resección-artroplastia de interposición debe intentarse en pacientes jóvenes en los que se quiera preservar la biomecánica normal del pie, evitándose los problemas a largo plazo de la artrodesis. La triple artrodesis o la artrodesis subastragalina, se reservan para pacientes mayores con signos degenerativos, en casos de fusio¬nes tarsianas múltiples y tras fracaso de la resección¬-artroplasti

The dynamic use of EGFR mutation analysis in cell-free DNA as a follow-up biomarker during different treatment lines in non-small-cell lung cancer patients

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9 5-13) to the best response (median = 0, IQR = 0-0, p < 0 01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0 01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received

Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation

BACKGROUND: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8. IL-8 importance in malignancies has been ascribed to angiogenesis promotion. PRINCIPAL FINDINGS: IL-8 effects on human monocyte-derived DC biology were explored upon DC exposure to recombinant IL-8 and with the help of an IL-8 neutralizing mAb. In vivo experiments were performed in immunodeficient mice xenografted with IL-8-producing human colon carcinomas and comparatively with cell lines that do not produce IL-8. Allogenic T lymphocyte stimulation by DC was explored under the influence of IL-8. DC and neutrophil chemotaxis were measured by transwell-migration assays. Sera from tumor-xenografted mice contained increasing concentrations of IL-8 as the tumors progress. IL-8 production by carcinoma cells can be modulated by low doses of cyclophosphamide at the transcription level. If human DC are injected into HT29 or CaCo2 xenografted tumors, DC are retained intratumorally in an IL-8-dependent fashion. However, IL-8 did not modify the ability of DC to stimulate T cells. Interestingly, pre-exposure of DC to IL-8 desensitizes such cells for IL-8-mediated in vitro or in vivo chemoattraction. Thereby DC become disoriented to subsequently follow IL-8 chemotactic gradients towards malignant or inflamed tissue. CONCLUSIONS: IL-8 as produced by carcinoma cells changes DC migration cues, without directly interfering with DC-mediated T-cell stimulation

Comparison of unidimensional and bidimensional measurements in metastatic non-small cell lung cancer

Tumour response evaluation after chemotherapy has become crucial in the development of many drugs. In contrast to the standard bidimensional WHO criteria, the recently described Response Evaluation Criteria In Solid Tumors are based on unidimensional measurements. The aim of the present study was to compare both methods in patients with metastatic non-small cell lung cancer. One hundred and sixty-four patients treated with two cisplatin-paclitaxel-based chemotherapy schedules between June 1994 and December 2000 were analysed. The measurements were reviewed by an independent panel of radiologists. Patient characteristics were: median age of 55 years (range 24–77 years) and a male to female ratio of 129 : 35. Adenocarcinoma and squamous carcinoma were the most common histologies. Vinorelbine was the third drug used in 77 patients and gemcitabine in 87. The ratio unidimensional/bidimensional was as follows: response 85 : 85; stable disease 32 : 32; progression 47 : 42 and not assessable 0 : 5. Kappa for agreement between responders was 0.951 (95% CI: 0.795–1.0) (P<0.001). Both WHO criteria and Response Evaluation Criteria In Solid Tumors give similar results in assessing tumour response in patients with non-small cell lung cancer after chemotherapy. The unidimensional measurement could replace the more complex bidimensional one

Strategies to design clinical studies to identify predictive biomarkers in cancer research

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework—the DESIGN guidelines—to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field