RESUMEN
Neoadjuvant treatment has become standard care for patients with resectable esophageal cancer. However, some patients cannot undergo surgery or curative resection because of disease progression during neoadjuvant treatment. The aim of this study is to identify the pretreatment characteristics of patients in whom neoadjuvant treatment failed. The study enrolled 231 patients who underwent chemotherapy with cisplatin and 5-fluorouracil (CF) as neoadjuvant therapy for T1N1-3 or T2-3 any-N esophageal squamous cell carcinoma (ESCC). Of these patients, 201 (87.0%) underwent curative resection (R0) and 30 (13.0%) could not undergo curative resection; 19 patients (8.2%) underwent incomplete resection (R1 or R2), and 11 patients (4.8%) could not undergo surgery because of disease progression. We compared clinical characteristics and survival between patients who underwent curative resection (curative group) and those who could not undergo curative resection (noncurative group) to determine the factors predicting noncurative treatment. The noncurative group had significantly worse disease-specific survival than the curative group (P < 0.001). All patients in the noncurative group had cT3 tumors. In 141 patients with cT3 tumors, those in the noncurative group were more likely to have higher serum SCC antigen concentration (P = 0.021), location of the main tumor in the upper to the middle third of the esophagus (P = 0.071), intramural metastases (P < 0.001), advanced N category (P = 0.016), and bulky lymph node metastases (P = 0.060). Multivariate logistic regression analysis identified location of the main tumor in the upper to the middle third of the esophagus (P = 0.047), intramural metastases (P = 0.002), and nodal metastases (N1, P = 0.014; N2, P = 0.015, respectively) as independent predictors of treatment failure in patients with cT3 tumors. Neoadjuvant CF therapy alone may not be effective for patients with cT3 tumors accompanied by these risk factors, and the efficacy of alternative strategies, such as triplet chemotherapy or chemoradiotherapy, should be evaluated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Anciano , Antígenos de Neoplasias/sangre , Carcinoma de Células Escamosas/secundario , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Esofagectomía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Retrospectivos , Serpinas/sangre , Tasa de Supervivencia , Insuficiencia del Tratamiento , Carga TumoralRESUMEN
A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLODâ=â4.51, αâ=â0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLODâ=â3.60, αâ=â0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLODâ=â3.07, αâ=â0.29; dominant HLODâ=â3.03, αâ=â0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLODâ=â3.02, αâ=â0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.
Asunto(s)
Mapeo Cromosómico , Neoplasias Colorrectales/genética , Ligamiento Genético , Adulto , Anciano , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 4 , Cromosomas Humanos Par 8 , Reparación de la Incompatibilidad de ADN , Familia , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Escala de Lod , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
The fascicular arrangement of the oculomotor nerve within the midbrain is not adequately elucidated in humans. We treated a patient with a partial oculomotor palsy who had impaired adduction and supraduction on the left side, which were attributed to an ipsilateral lacunar infarct. CT and MRI revealed a discrete lesion in the centre of the midbrain tegmentum in the rostrocaudal plane. This case suggests that the oculomotor fibres for extraocular movement are located in the middle of the the midbrain, and supports the fascicular proximity of the superior and medial rectus muscles. The fascicular arrangement of the midbrain oculomotor nerve is speculated to be pupillary component, extraocular movement and eyelid elevation in that rostrocaudal order, based on the previous reports of neuro-ophthalmological impairment and MRI findings, which are analogous to the nuclear arrangement proposed by Warwick.