BackgroundScreening is the main preventive method for cervical cancer in developing countries, but each type of screening has advantages and disadvantages. To investigate the most suitable method for low-income areas in China, we conducted a health economic analysis comparing three methods: visual inspection with acetic acid and Lugol’s iodine (VIA/VILI), ThinPrep cytology test (TCT), and human papillomavirus (HPV) test.MethodsWe recruited 3086 women aged 35–65 years using cluster random sampling. Each participant was randomly assigned to one of three cervical cancer screening groups: VIA/VILI, TCT, or HPV test. In order to calculate the number of disability-adjusted life years (DALYs) averted by each screening method, we used Markov models to estimate the natural development of cervical cancer over a 15-year period to estimate the age of onset and duration of each disease stage. The cost-effectiveness ratios (CERs), net present values (NPVs), benefit-cost ratios (BCRs), and cost-utility ratios (CURs) were used as outcomes in the health economic analysis.ResultsThe positive detection rate in the VIA/VILI group was 1.39%, which was 4.6 and 2.0 times higher than the rates in the TCT and HPV test groups, respectively. The positive predictive value of VIA/VILI (10.53%) was highest while the rate of referral for colposcopy was lowest for those in the HPV + TCT group (0.60%). VIA/VILI performed the best in terms of health economic evaluation results, as the cost of per positive case detected was 8467.9 RMB, which was 24503.0 RMB lower than that for TCT and 5755.9 RMB lower than that for the HPV test. In addition, the NPV and BCR values were 258011.5 RMB and 3.18 (the highest), and the CUR was 2341.8 RMB (the lowest). The TCT performed the worst, since its NPV was <0 and the BCR was <1, indicative of being poorly cost-beneficial.ConclusionsWith the best economic evaluation results and requiring minimum medical resources, VIA/VILI is recommended for cervical cancer screening in poverty-stricken areas in China with high incidence of cervical cancer and lack of medical resources.
Previous studies only focused on different adverse reactions caused by various platinum drugs, but not on common immunotoxicity caused by the accumulation of elemental platinum. Here, we determined the serum platinum concentrations of cancer patients after a metabolism period of platinum drug chemotherapy, in addition to hematological indices and subsequent immune-related adverse reactions, then analyzed the correlations between platinum accumulation, immune cell levels, and immune-toxicity. We chose the day before the next round of chemotherapy as the specified time point for blood sampling. Samples were collected at five time points, separately in oxaliplatin and cisplatin groups. The median serum platinum concentrations in all patients was 294.8 (205.6, 440.3) mg/L, and was approximately twofold greater in the cisplatin group than in the oxaliplatin group (429.3 vs. 211.7 mg/L). The platinum level of both groups peaked at the third time point, with the average of females being higher than males (383.9 vs. 266.5 mg/L), and was positively correlated with leukocyte and platelet counts, but negatively correlated with erythrocyte counts and concentration of hemoglobin. The risks of anemia and adverse reactions were individually increased by 0.002-and 0.007-fold for every mg/L increase of platinum concentration. To our knowledge, this is the first study on the relationship between platinum accumulation, immune cell levels and toxicity, showing that drug-induced platinum accumulation may interfere with immune cells and thus increase the risk of toxicity.
Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.
Gastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect patients’ quality of life, and the role of metabolites in gastric cancer prognosis has not been sufficiently understood. We aimed to establish a prognostic prediction model for GC patients based on a metabolism-associated signature and identify the unique role of metabolites in the prognosis of GC. Thus, we conducted untargeted metabolomics to detect the plasma metabolites of 218 patients with gastric adenocarcinoma and explored the metabolites related to the survival of patients with gastric cancer. Firstly, we divided patients into two groups based on the cutoff value of the abundance of each of the 60 metabolites and compared the differences using Kaplan–Meier (K-M) survival analysis. As a result, 23 metabolites associated with gastric cancer survival were identified. To establish a risk score model, we performed LASSO regression and Cox regression analysis on the 60 metabolites and identified 8 metabolites as an independent prognostic factor. Furthermore, a nomogram incorporating clinical parameters and the metabolic signature was constructed to help individualize outcome predictions. The results of the ROC curve and nomogram plot showed good predictive performance of metabolic risk features. Finally, we performed pathway analysis on the 24 metabolites identified in the two parts, and the results indicated that purine metabolism and arachidonic acid metabolism play important roles in gastric cancer prognosis. Our study highlights the important role of metabolites in the progression of gastric cancer and newly identified metabolites could be potential biomarkers or therapeutic targets for gastric cancer patients.
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