Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. METHODS: Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. RESULTS: Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. CONCLUSIONS: Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Influence of skeletal muscle and intermuscular fat on postoperative complications and long-term survival in rectal cancer patients.

BACKGROUND: The body composition of patients with rectal cancer potentially affects postoperative outcomes. This study explored the correlations between skeletal muscle and adipose tissue quantified by computed tomography (CT) with postoperative complications and long-term prognosis in patients with rectal cancer after surgical resection. METHODS: This retrospective cohort study included patients with rectal cancer who underwent surgical resection at the Wuhan Union Hospital between 2014 and 2018. CT images within 3 months prior to the surgery were used to quantify the indices of skeletal muscle and adipose tissue at the levels of the third lumbar vertebra (L3) and umbilicus. Optimal cut-off values for each index were defined separately for males and females. Associations between body composition and postoperative complications, overall survival (OS), and disease-free survival (DFS) were evaluated using logistic and Cox proportional hazards models. RESULTS: We included 415 patients (240 males and 175 females; mean age: 57.8 ± 10.5 years). At the L3 level, a high skeletal muscle density (SMD; hazard ratio [HR]: 0.357, 95% confidence interval [CI]: 0.191-0.665, P = 0.001; HR: 0.571, 95% CI: 0.329-0.993, P = 0.047) and a high skeletal muscle index (SMI; HR: 0.435, 95% CI 0.254-0.747, P = 0.003; HR: 0.568, 95% CI: 0.359-0.897, P = 0.015) were independent prognostic factors for better OS and DFS. At the umbilical level, a large intermuscular fat area (IMFA; HR: 1.904, 95% CI: 1.068-3.395, P = 0.029; HR: 2.064, 95% CI: 1.299-3.280, P = 0.002) was an independent predictive factor for worse OS and DFS, and a high SMI (HR: 0.261, 95% CI: 0.132-0.517, P < 0.001; HR: 0.595, 95% CI: 0.387-0.913, P = 0.018) was an independent prognostic factor for better OS and DFS. The models combining body composition and clinical indicators had good predictive abilities for OS. The receiver operating characteristic areas under the curve were 0.848 and 0.860 at the L3 and umbilical levels, respectively (both P < 0.05). CONCLUSIONS: No correlations existed between CT-quantified body composition parameters and postoperative complications. However, a high SMD and high SMI were significantly associated with longer OS and DFS at the L3 level, whereas a large IMFA and low SMI were associated with worse OS and DFS at the umbilical level. Combining CT-quantified body composition and clinical indicators could help physicians predict the prognosis of patients with rectal cancer after surgery.

Effect-directed analysis of estrogenic chemicals in sediments from an electronic-waste recycling area.

Electronic waste (e-waste) pollution is of great concern due to the release of hazardous chemicals during the improper e-waste disposal. Many chemicals leached from e-waste were reported to pose estrogenic effects. To date, little is known regarding the occurrence and biological effects of estrogenic chemicals in sediments near an e-waste area. In this study, an effect-directed analysis (EDA) is applied to determine the estrogenic chemicals in sediments of four sites collected from a typical e-waste recycling city in China. Following screening with the ER-CALUX assay, the extract of sample with the most potent effect was subjected in fractionation using reverse phase liquid chromatography. Based on a target analysis for the active fractions, four compounds, including estrone, 17ß-estradiol, 17α-ethinylestradiol and bisphenol A, were identified, and these contributed to 17% of the total toxic effects in the sample. A further nontarget analysis screened four candidates, namely diethylstilbestrol (DES), hexestrol (HES), nandrolone and durabolin, and the total contribution was found to be 48% from the active sample. Specifically, DES and HES were only detected in the active sample and were found to be the primary drivers of estrogenic effects. An examination of the identified chemicals in the four sites indicated that these estrogenic chemicals may originate from e-waste recycling, livestock excretion and domestic waste. These findings uncovered the estrogenic pollutants in sediments from an e-waste area. Considering single endpoint in biological assay is not abundant to screen chemicals with different toxic effects, further EDA studies with multiple endpoints are required to better understand the occurrence of representative or unknown chemicals in e-waste-polluted areas.

Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation.

AIMS: In recent years, more and more people are suffering from lifestyle-related disease such as nonalcoholic fatty liver disease (NAFLD) because of unhealthy diet and lack of physical exercise. Hesperidin (HDN) is a flavonoid found in high concentrations in citrus fruits. In this study, we investigated the effect of HDN on NAFLD, providing information to develop dietary supplements for NAFLD treatment and prevention. MATERIALS AND METHODS: Testing kits, hematoxylin-eosin staining, oil red O staining, western blot, immunofluorescence, cck-8 assay, and blood biochemical analysis were carried out during the experiments in vivo and in vitro. KEY FINDINGS: The current study revealed that HDN significantly reduced liver index and serum lipid levels, and protected against liver steatosis and injury induced by HFD. In addition, HDN suppressed oil acid induced intracellular lipid accumulation in HepG2 cells. Moreover, HDN increased the expression level of pAMPK and downregulated SREBP-1C, ACC and FAS expression in vivo and in vitro. SIGNIFICANCE: In summary, HDN attenuates lipid accumulation in vivo and in vitro via AMPK activation, suggesting that HDN may serve as a potential therapeutic agent for treating NAFLD.