Influence of CASP9 c.-1339A>G and CASP3 c.-1191A>G variants in outcome of patients with head and neck squamous cell carcinoma.

BACKGROUND: Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whether CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty-two HNSCC patients were enrolled in the study. METHODS: DNA and RNA of peripheral blood samples were analyzed using real-time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences in CASP3 expressions were analyzed using the Mann-Whitney test. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier curves, log-rank test, and Cox analyses. RESULTS: CASP3 c.-1191AG or GG genotype was associated with higher CASP3 expression when compared with AA genotype (0.50 arbitrary units (AUs) ± 0.29 standard deviation (SD) vs 0.28 AUs ± 0.12 SD; P = .02). Patients with CASP9 c.-1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients with CASP9 c.-1339AA or AG genotype. Patients with CASP9 c.-1339GG and CASP3 c.-1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes. CONCLUSIONS: Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs, act as predictors of HNSCC patients' survival.

Advanced Esophageal Neoplasm with Subcutaneous Metastasis.

OBJECTIVE: This report is aimed at describing a rare clinical condition of advanced esophageal cancer with subcutaneous metastasis. CASE REPORT: The present case refers to a patient diagnosed with stage IV esophageal squamous cell carcinoma which started with dysphonia and cervical nodules. Soon after that, the patient developed dysphagia and subcutaneous lesions on the right flank. Later in time, we documented a disease progression, with worsening of subcutaneous implants, lymph node, bone, and pulmonary metastases in addition to malignant hypercalcemia. CONCLUSION: This illustrates a rare presentation of an advanced esophageal neoplasm. Subcutaneous metastasis from internal malignancies is unusual, corresponding to less than 10% of cases. Its occurrence in patients with esophageal cancer is even less common with very few cases reported in literature.

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma.

PURPOSE: We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis. METHODS: Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses. RESULTS: XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02). CONCLUSIONS: Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.

Neoadjuvant endocrine therapy for resectable breast cancer: A systematic review and meta-analysis.

INTRODUCTION: The role of neoadjuvant endocrine therapy for resectable breast cancer is not well established, despite encouraging results obtained in the metastatic and adjuvant settings. This systematic review aims to examine existing medical literature on neoadjuvant hormone therapy (HT). METHODS: Data from prospective, randomized trials was included if comparing neoadjuvant HT versus surgery alone without adjuvant treatment, or neoadjuvant HT versus chemotherapy (CT), or HT plus CT versus CT alone, or HT plus CT versus HT alone, or two distinct HT. Odds Ratios (OR) were calculated from pooled data. RESULTS: Five studies compared HT with tamoxifen versus HT with aromatase inhibitors (AI). A meta-analysis of their results demonstrated superiority of AIs in overall response rate (ORR) (OR 1.9; 95% CI 1.17-3.08). Two trials compared HT against CT, and pooled data from them demonstrated a trend favoring CT (OR for ORR 0.75; 95% CI 0.35-1.6). That trend disappeared when only postmenopausal women were considered (OR 1.01; 95% CI 0.62-1.63). One trial compared HT plus CT with no neoadjuvant treatment, and obtained an 83% ORR. One trial compared HT plus CT versus CT alone and found a non-significant increase in ORR for adding HT to CT (OR 1.48; 95% CI 0.58-3.77). No trial compared HT plus CT versus HT alone. CONCLUSIONS: Neoadjuvant HT is a safe and feasible option, but it cannot be considered equivalent to CT. If neoadjuvant HT is performed, AIs are preferable over tamoxifen due to higher response rates.

Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma.

We examined the influence of MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A and EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR-RFLP or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p = 0.003) genotypes were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the respective combined genotype were under a 3.69 (95% CI: 1.54-8.81)-fold increased risk of LSCC. Interactions of tobacco and tobacco plus all the above-mentioned polymorphisms on HNSCC and LSCC risk were also evident in study (p = 0.001). At 60 months of follow-up, relapse-free survival (RFS) was shorter in patients with EXO1 GG genotype (54.8% vs. 61.1%, p = 0.03) and overall survival (OS) was shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p = 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03-2.20, p = 0.03) and OS (HR: 1.59, 95% CI: 1.19-2.13, P = 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, and EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes.

Trombose aguda de aneurisma de artéria femoral isolado: relato de caso / Acute thrombosis of isolated femoral artery aneurysm: case report

Aneurismas de artéria femoral são raros, porém são o segundo tipo mais freqüente de aneurismas periféricos, sendo o aneurisma de artéria poplítea o mais comum. Normalmente, são de etiologia aterosclerótica. As complicações deste aneurisma são representadas por embolia, trombose e, mais raramente, a rotura. O objetivo deste trabalho é relatar um caso de um paciente com 59 anos, masculino, com queixa de dor súbita em membro inferior esquerdo associado à frialdade, palidez e ausência de pulsos. O ecocolordoppler evidenciou a presença de aneurisma trombosado da artéria femoral comum. O paciente foi submetido, com sucesso, à ressecção do aneurisma, com reconstrução do leito arterial.

Common femoral artery aneurysms are rare; however, they are the second most frequent type of peripheral aneurysm, popliteal artery aneurysms being the most common. They usually have atherosclerotic ethiology. The complications of this aneurysm are thromboembolism and, more rarely, rupture. This article aimed at reporting the case of a 59-year-old male patient with complaint of sudden pain in his left leg associated with coldness, paleness and absence of pulses. Color Doppler ultrasound showed a thrombosed aneurysm of the common femoral artery. The patient was successfully submitted to aneurysm resection with reconstruction of the arterial bed.