RESUMEN
Chlorpyrifos (CPF) biocide, exposure to which is mainly produced in the human population through diet, induces several neurotoxic effects. CPF single and repeated exposure induces memory and learning disorders, although the mechanisms that produce these outcomes are complex and not well understood. CPF treatment (single and repeated) of cholinergic septal SN56 cells induced an increase in phosphorylated-P38α levels that led to WNT/ß-Catenin and NGF/P75NTR/TrkA pathways disruption and cell death. These results provide new knowledge on the mechanisms that mediate CPF basal forebrain cholinergic neuronal loss induced by CPF single and repeated exposure and can help unravel the way through which this compound produces cognitive decline and develop efficient treatments against these effects.
RESUMEN
BACKGROUND/AIMS: The majority of the time extended liver resections cannot be realized because of an insufficient future remnant liver. Baumgart suggests recently combining liver partition and portal vein section for staged hepatectomy, named ALPPS procedure. Our aim is to share our initial experience with ALPPS procedure and to perform the first comprehensive English literature review. METHODOLOGY: From January 2011 until June 2013, 6 patients underwent ALPPS, performing 6 extended right hepatectomies (one with concomitant right colectomy, one with main biliary duct resection). RESULTS: The present series showed a mean of 110% volume hypertrophy of the future remnant liver achieved with a mean of 15.3 days after ALPPS. One patient experienced severe liver failure, one had biliary leak and one died for postoperative respiratory distress syndrome. After a mean followup of 16.2 months (range 2-30 months) one patient had liver recurrence. In an English literature search, we identified 18 publications describing a mean hypertrophy rate of 85%, a mean morbidity and mortality rate of 35% and 6%, respectively. CONCLUSIONS: ALPPS is an effective technique used to induce an increased and rapid growth of the future remnant liver, but at the price of a higher morbidity and mortality compared with other conventional procedures.
Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Conducto Colédoco/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Regeneración Hepática , Vena Porta/cirugía , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Neoplasias Colorrectales/patología , Conducto Colédoco/patología , Resultado Fatal , Femenino , Hepatectomía/efectos adversos , Humanos , Hipertrofia , Ligadura , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.
RESUMEN
PURPOSE: Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. PATIENTS AND METHODS: Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. RESULTS: In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). CONCLUSION: The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.