Jinhu Fan

BACKGROUND The survival rate of pancreatic cancer is low, and there is a lack of effective treatment. AIM To explore the epidemiological characteristics of patients with pancreatic cancer in China and compare multiple chemotherapy regimens at different stages. METHODS This was a retrospective study conducted from 2005 to 2014, involving six cancer hospitals and eight general hospitals across seven geographical regions of China (East, South, North, Central, Southwest, Northwest, and Northeast). Stratified sampling was used based on the population distribution of each region. Efficacy assessments were conducted by Cox proportional hazards regression models. When assessing the effectiveness of various chemotherapy regimens, traditional drugs such as gemcitabine used as monotherapy served as the reference. RESULTS A total of 3256 patients were included. The median follow-up time was 407 days, and the median overall survival was 183 days. At diagnosis, 56% of patients were already in stage IV. Chemotherapy was administered to 39.73% of patients. In the adjuvant therapy phase, gemcitabine + fluorouracil was superior to gemcitabine monotherapy [hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.14-0.89]. In fluorouracil-based regimens, other combination regimens did not show effectiveness relative to monotherapy. For first-line treatment in patients with advanced disease, tegafur alone (HR = 0.20, 95%CI: 0.06-0.66), gemcitabine plus cisplatin (HR = 0.16, 95%CI: 0.04-0.70), and tegafur, gemcitabine plus platinum-based agents (HR = 0.32, 95%CI: 0.11-0.91) were associated with a lower risk of death compared to gemcitabine alone. In second-line treatment, there were no significant differences in efficacy among various drugs, but FOLFIRINOX (irinotecan + oxaliplatin + leucovorin + 5-fluorouracil) had an outstanding point estimate (HR = 0.10, 95%CI: 0.01-1.27). CONCLUSION In China, pancreatic cancer is often diagnosed at advanced stages, emphasizing the need for early diagnosis and treatment. Combined therapies in adjuvant and first-line settings may reduce the risk of death compared with monotherapy, and FOLFIRINOX might offer more significant benefits in second-line treatment.

Esophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case–control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators. Graphical abstract

Background: Whether the dynamic weight change is an independent risk factor for mortality remains controversial. This study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial (NIT) cohort. Methods: Body weight of 21,028 healthy residents of Linxian, Henan province, aged 40–69 years was measured two times from 1986 to 1991. Outcome events were prospectively collected up to 2016. Weight maintenance group (weight change All-cause = 1.14, 95% CI: 1.09–1.19, P Cancer = 1.12, 95% CI: 1.03–1.21, P = 0.009), and heart disease (HR_{Heart diseases} = 1.21, 95% CI: 1.11–1.31, P Cancer = 0.89, 95% CI: 0.79–0.99, P = 0.033) lower risk of cancer mortality and 23% higher risk of stroke mortality (HR_Stroke = 1.23,95% CI: 1.12–1.34, P Overweight to normal = 1.18, 95% CI: 1.09–1.27; HR_{Becoming underweight} = 1.35, 95% CI: 1.25–1.46) and cancer death (HR_{Overweight to normal} = 1.20, 95% CI: 1.04–1.39; HR_{Becoming underweight} = 1.44, 95% CI: 1.24–1.67), while stable overweight could increase the risk of total death (HR_{Stable overweight} = 1.11, 95% CI: 1.05–1.17) and death from stroke (HR_{Stable overweight} = 1.44, 95% CI: 1.33–1.56). Interaction effects were observed between age and weight change on cancer mortality, as well as between baseline BMI and weight change on all-cause, heart disease, and stroke mortality (all P _interaction <0.01). Conclusions: Weight loss was associated with an increased risk of all-cause, cancer, and heart disease mortality, whereas excessive weight gain and stable overweight were associated with a higher risk of stroke mortality. Efforts of weight management should be taken to improve health status. Trial registration: https://classic.clinicaltrials.gov/, NCT00342654.

Background: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. Results: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86–0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82–0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All P_interaction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (P_interaction = 0.03). No association was observed between drinking water source and GC incidence. Conclusions: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. Trial registration: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

The optimal treatment regimen for breast cancer patients with gBRCA mutations remains controversial given the availability of numerous options, such as platinum-based agents, polymerase inhibitors (PARPis), and other agents. We included phase II or III RCTs and estimated the HR with 95% CI for OS, PFS, and DFS, in addition to the OR with 95% CI for ORR and pCR. We determined the treatment arm rankings by P-scores. Furthermore, we carried out a subgroup analysis in TNBC and HR-positive patients. We conducted this network meta-analysis using R 4.2.0 and a random-effects model. A total of 22 RCTs were eligible, involving 4253 patients. In the pairwise comparisons, PARPi + Platinum + Chemo was better than PARPi + Chemo for OS (in whole study group and in both subgroups) as well as PFS. The ranking tests demonstrated that PARPi + Platinum + Chemo ranked first in PFS, DFS, and ORR. Platinum + Chemo showed higher OS than PARPi + Chemo. The ranking tests for PFS, DFS, and pCR indicated that, except for the best treatment (PARPi + Platinum + Chemo) containing PARPi, the second and third treatments were platinum monotherapy or platinum-based chemotherapy. In conclusion, PARPi + Platinum + Chemo might be the best regime for gBRCA-mutated BC. Platinum drugs showed more favorable efficacy than PARPi in both combination and monotherapy.