Epithelial growth factor receptor (EGFR) mutations are present in 10%-26% of non-small cell lung cancer (NSCLC) tumors and are associated with the response to tyrosine kinase inhibitors (TKIs). This study aimed to detect and quantify the presence of circulating tumor cells (CTCs) in EGFR-mutant NSCLC patients and investigate their possible role in providing prognostic information. Enrolled patients received erlotinib (150 mg) or gefitinib (250 mg) orally once daily as the first-line treatment. Serial blood samples were taken at baseline (CTC-d0) and on day 28 (CTC-d28) following the initiation of erlotinib/gefitinib for detection of CTCs using the CellSearch system. CTCs ≥2 were found in 47/107 (44%) and CTCs ≥5 in 17/107 (15%). The CTC measurements were dichotomized as favorable (<5 CTCs) and unfavorable (≥5 CTCs) groups. The median progression-free survival (PFS) interval for patients in the favorable group at baseline was 11.1 months, significantly longer than the median PFS time of 6.8 months achieved by patients in the unfavorable group (p = 0.009). Patients in the favorable group on day 28 exhibited significantly longer PFS compared with patients in the unfavorable group (11.6 vs. 6.3 months; p < 0.0001). In univariate analysis, CTC-d0 ≥ 5 versus CTC-d0 = 0-4 was significantly associated with poor PFS and time-to-treatment failure (TTF). CTC-d28 ≥ 5 versus CTC-d28 = 0-4 was significantly associated with a poor PFS outcome. CTC-d0 and CTC-d28 remained independent poor prognostic markers in the stepwise multivariate analysis. Our study indicates that the CTC count is a prognostic factor for PFS and TTF outcomes in patients with advanced EGFR-mutant NSCLC.
Background and study aims: To assess the efficacy and clinical outcomes of endoscopic retrograde appendicitis therapy (ERAT) versus laparoscopic appendectomy (LA) for patients with uncomplicated acute appendicitis (AA). Patients and methods: We adopted propensity score matching (1:1) to compare ERAT and LA patients with uncomplicated AA from April 2017 to March 2020. We reviewed a total of 2880 patients with suspected acute appendicitis, of whom 422 patients with uncomplicated AA met the matching criteria (ERAT, 79; LA, 343), yielding 78 pairs of patients. Results: The rate of curative treatment within one year after ERAT was 92.1%; 95% CI, [83.8% - 96.3%]. The percentage of Visual Analog Scale (VAS) ≤ 3 at six hours after treatment was 94.7%; 95% CI [87.2% - 97.9%] in the ERAT group, and significantly higher than that in the LA group 83.3%; 95% CI [73.5% - 90.0%]. Median operative/procedure time and median hospital length of stay in the ERAT group were significantly lower compared to the LA group. At one year, the median recurrence time was 50 days (IQRs, 25-127) in the ERAT group. The overall adverse event rate was 24.3%; 95% CI [14.8% - 33.9%] in the LA group and 18.4%; 95% CI [9.7% - 27.1%] in the ERAT group, with no significant difference between the two groups. Conclusions: ERAT is a technically feasible method to treat uncomplicated AA compared to LA.
There have been a few epidemiological studies reporting VDR polymorphisms including Fok1, Bsm1, Apa1 and Taq1with breast cancer incidence and therefore risk. The results however are controversial, often due to smaller sample size. Concerning most of the studies were performed on Caucasian women, we conducted this comprehensive meta-analysis encompassing 38,151 cases and 47,546 controls (Fok1: 13,152 cases, 17,443 controls; Bsm1: 14,755 cases, 18,633 controls; Apa1: 3080 cases, 3412 controls; Taq1: 7164 cases, 8068 controls) to better understand roles of the polymorphisms in breast cancer development among Caucasian population. We did not find any association of the most controversial genotype Fok1 with breast cancer risk in Caucasian women (ff vs. FF: OR = 1.05, 95% CI = 0.95–1.22, P = 0.32 for heterogeneity; ff vs. Ff: OR = 1.05, 95% CI = 0.94–1.17, P = 0.40; ff vs. Ff + FF: OR = 1.07, 95% CI = 0.95–1.14, P = 0.37 and ff + Ff vs. FF: OR = 1.04, 95% CI = 0.99–1.09, P = 0.23). For Bsm1, Apa1 and Taq1, no significant association was also not found in the homozygote comparison, heterozygote comparison, recessive and dominant models respectively. In conclusion, the current analysis suggested that the four polymorphisms (Fok1, Bsm1, Apa1 and Taq1) of VDR may be not associated with breast cancer risk in Caucasian women.
Cytotoxic T-lymphocyte antigen (CTLA-4) plays an important role in downregulating T cell activation and proliferation. The CTLA-4 + 49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with many cancer types, but the association between CTLA-4 + 49G > A polymorphism and digestive system cancer risks remain inconclusive. An updated meta-analysis based on 17 independent case–control studies consisting of 5176 cancer patients and 6747 controls was performed to address this association. Overall, there was no statistically increased risk of digestive system cancers in every genetic comparison. In subgroup analysis, this polymorphism was significantly linked to higher risks for pancreatic cancer (GG vs. AA, OR = 1.976, 95% CI = 1.496–2.611; GA vs. AA, OR = 1.433, 95% CI = 1.093–1.879; GG/GA vs. AA, OR = 1.668, 95% CI = 1.286–2.164; GG vs. GA/AA, OR = 1.502, 95% CI = 1.098–2.054; G vs. A, OR = 1.394, 95% CI = 1.098–1.770). We also observed increased susceptibility of hepatocellular cell carcinoma in homozygote comparison (OR = 1.433, 95% CI = 1.100–1.866) and dominant model (OR = 1.360, 95% CI = 1.059–1.746). According to the source of controls, significant effects were only observed in hospital-based studies (GA/AA vs. GG, OR = 1.257, 95% CI = 1.129–1.399). In the stratified analysis by ethnicity, no significantly increased risks were found in either Asian or Caucasian. Our findings suggest that the CTLA-4 + 49G > A polymorphism may be associated with the risk of pancreatic cancer and hepatocellular cell carcinoma.
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