RESUMEN
Objective: Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). Methods: We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Result: Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. Conclusion: The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.
RESUMEN
Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41-0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38-0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40-4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.
