CNDP2

The value of neoadjuvant chemoradiotherapy (CRT) is not absolutely clear for upper-half (> 7-15 cm) rectal cancer. This study aimed to compare the efficacy and safety of radical surgery with preoperative CRT vs. upfront surgery (US) in Chinese patients with stage II and III upper-half rectal cancer. A total of 809 patients with locally advanced upper-half rectal cancer between 2017 and 2021 were enrolled retrospectively (280 treated with CRT and 529 treated with US). Through 1:1 propensity score matching, the CRT (172 patients) and US (172 patients) groups were compared for short-term postoperative results and long-term oncological and functional outcomes. In the entire cohort, patients in the CRT group had a younger age, lower distance from the anal verge (DAV), and higher rates of cT4 stage, cN2 stage, mrCRM positivity, EMVI positivity, CEA elevation, and CA-199 elevation than those in the US group. The 5-year disease-free survival (DFS) was lower in the CRT group than in the US group (76% vs. 84%, p = 0.022), while the 5-year overall survival (OS) was comparable between the two groups (85% and 88%, p = 0.084). The distant metastasis rate was higher in the CRT group than in the US group (12.5% vs. 7.8%, p = 0.028), though the local recurrence rate was similar between the two groups (1.1% and 1.3%, p = 1.000). After performing PSM, the 5-year OS (86% vs. 88% p = 0.312), the 5-year DFS (79% vs. 80%, p = 0.435), the local recurrence rate (1.2% vs. 1.7%, p = 1.000), and the distant metastasis rate (11.0% vs. 9.3%, p = 0.593) were comparable between the two groups. Notable pathological downstaging was observed in the CRT group, with a pathological complete response (PCR) rate of 14.5%. In addition, patients in the CRT group had a lower proportion of pT3 (61.6% vs. 77.9%, p < 0.001), pN + (pN1, 15.1% vs. 30.2%, pN2, 9.3% vs. 20.3%, p < 0.001), stage III (24.4% vs. 50.6%, p < 0.001), perineural invasion (19.8% vs. 32.0%, p = 0.014), and lymphovascular invasion (9.3% vs. 25.6%, p < 0.001) than those in the US group. Postoperative complications and long-term functional results were similar, yet there was a trend toward a higher conversion to laparotomy rate (5 (2.9%) vs. 0 (0.0%), p = 0.061) and higher rates of robotic surgery (11.6% vs. 4.7%, p < 0.001), open surgery (7.0% vs. 0.6%, p < 0.001), diverting stoma (47.1% vs. 25.6%, p < 0.001), and surgery costs (1473.6 ± 106.5 vs. 1140.3 ± 54.3$, p = 0.006) in the CRT group. In addition, EMVI (OR = 2.516, p = 0.001) was the only independent risk factor associated with poor response to CRT, and in subgroup analysis of EMVI + , CRT group patients presented a lower 5-year DFS (72.9% vs. 80.5%, p = 0.025) compared to US group patients. CRT prior to surgery has no additional oncological benefits over US in the treatment of upper-half rectal cancer. In contrast, CRT is associated with increased rates of conversion to laparotomy, stoma creation and higher surgery costs. Surgeons tend to favor robotic surgery in the treatment of complex cases such as radiated upper-half rectal cancers. Notably, EMVI + patients with upper-half rectal cancer should be encouraged to undergo upfront surgery, as preoperative CRT may not provide benefits and may lead to delayed treatment effects.

A fluorochemical facility near Fayetteville, North Carolina, emitted per- and polyfluoroalkyl ether acids (PFEAs), a subgroup of per- and polyfluoroalkyl substances (PFAS), to air.

Analyze PFAS in private wells near the facility and in blood from well users to assess relationships between PFEA levels in water and serum.

In 2019, we recruited private well users into the GenX Exposure Study and collected well water and blood samples. We targeted 26 PFAS (11 PFEAs) in water and 27 PFAS (9 PFEAs) in serum using liquid chromatography-mass spectrometry. We used regression modeling to explore relationships between water and serum PFAS. For the only PFEA detected frequently in water and serum, Nafion byproduct 2, we used generalized estimating equation (GEE) models to assess well water exposure metrics and then adjusted for covariates that may influence Nafion byproduct 2 serum concentrations.

We enrolled 153 participants ages 6 and older (median = 56 years) using 84 private wells. Most wells (74%) had ≥6 detectable PFEAs; median ∑PFEAs was 842 ng/L (interquartile range = 197-1760 ng/L). Low molecular weight PFEAs (PMPA, HFPO-DA [GenX], PEPA, PFO2HxA) were frequently detected in well water, had the highest median concentrations, but were not detectable in serum. Nafion byproduct 2 was detected in 73% of wells (median = 14 ng/L) and 56% of serum samples (median = 0.2 ng/mL). Cumulative dose (well concentration × duration at address) was positively associated with Nafion byproduct 2 serum levels and explained the most variability (10%). In the adjusted model, cumulative dose was associated with higher Nafion byproduct 2 serum levels while time outside the home was associated with lower levels.

PFAS are a large class of synthetic, fluorinated chemicals. Fluorochemical facilities are important sources of environmental PFAS contamination globally. The fluorochemical industry is producing derivatives of perfluoroalkyl acids, including per- and polyfluoroalkyl ether acids (PFEAs). PFEAs have been detected in various environmental samples but information on PFEA-exposed populations is limited. While serum biomonitoring is often used for PFAS exposure assessment, serum biomarkers were not good measures of long-term exposure to low molecular weight PFEAs in a private well community. Environmental measurements and other approaches besides serum monitoring will be needed to better characterize PFEA exposure.

Imidazole dipeptides possess important bioregulatory properties in animals. This study aimed to evaluate the effect of high ambient temperature on muscle imidazole dipeptides (carnosine, anserine, and balenine) in broiler chickens. Sixteen 14-day-old male broiler chickens were divided into two groups, which were reared under thermoneutral (25 ± 1 °C) or cyclic high ambient temperature (35 ± 1 °C for 8 h/day) for 4 weeks. Chickens exposed to cyclic high ambient temperatures displayed lower skeletal muscle anserine and carnosine content than control chickens. Balenine could not be detected in the pectoral muscle of either group. The pectoral muscles of broiler chickens kept under cyclic high-temperature exhibited significantly lower mRNA expression of carnosine synthase 1, which synthesizes carnosine and anserine; but a significantly higher mRNA expression of carnosinase 2, which degrades carnosine and anserine. Our results suggest that heat exposure decreases pectoral imidazole dipeptide content in broiler chickens. This may be attributed to a lower expression of imidazole dipeptide-synthesizing genes, but higher levels of genes involved in their degradation.