Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Efficacy of silymarin-phospholipid complex in reducing the toxicity of aflatoxin B1 in broiler chicks.

Silymarin, the standardized extract of Silybum marianum, is used as a hepatoprotector in man, and is a potent antihepatotoxic agent. This study focused on the effects of a silymarin-phospholipid complex in reducing the toxic effects of aflatoxin B1 (AFB1) in broiler chickens. Twenty-one 14-d-old male commercial broilers were randomly allotted to 3 groups and treated as follows: basal diet alone [Group C (Control)]; AFB1 at 0.8 mg/kg of feed [Group B1]; AFB1 at 0.8 mg/kg of feed plus silymarin phytosome, a silymarin complexed form with phospholipids from soy, at 600 mg/kg of BW [Group B1+Sil]. Considering the whole growth cycle, BW gain and feed intake were lower in AFB1-treated birds with respect to controls (P < 0.05). In the B1+Sil group, BW gain and feed intake were higher with respect to birds receiving AFB1 alone (P < 0.05), and not different from the control birds. Serum biochemistry showed no difference among groups, except for a decrease of alanine amino transferase (ALT) in chicks treated only with AFB1. Alanine amino transferase activity in AFB1 plus silymarin phytosome treated birds was not different from the controls. No treatment differences were noted on liver weight. In conclusion, our results suggest that silymarin phytosome can provide protection against the negative effects of AFB1 on performance of broiler chicks.

Silymarin, a possible hepatoprotector in dairy cows: biochemical and histological observations.

Silymarin, a standardized extract from Silybum marianum seed, is a natural hepatoprotector used for the treatment of liver diseases in man. The aim of this study was to investigate its safety and efficacy in periparturient dairy cows. Ten treated and 10 control pregnant dairy cows were paired by parity, body condition score (BCS), health condition and previous milk production. Treatment consisted of daily 10 g per animal of silymarin extract administered as oral drenches, from 10 days prior to the calving date to 15 days after calving. Blood samples and liver biopsies were taken from each animal at 7 and 30 days after calving. Hepatic functions were evaluated by assay of plasma beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoproteins, low-density lipoproteins, triglyceride and total bilirubin. The histological aspect of the liver was assessed in biopsies. Clinical chemistry values were similar for both groups and effects at different times (day 7 versus day 30; P < 0.05) were attributed to physiological variations in periparturient cows. Histology showed fat accumulation in the liver of both groups, as it is expected in periparturient dairy cows. In treated cows, fat-rich hepatocytes were observed near the central vein. These observations suggest that, at the used dosage, S. marianum extract has no adverse effect on the liver of lactating cows, and presents no objective evidence for a hepatoprotective effect in this species.

Effects of silymarin, a natural hepatoprotector, in periparturient dairy cows.

Silymarin, a natural acknowledged hepatoprotector used in humans to treat liver diseases, has been tested in dairy cows during peripartum, a period during which animals are subject to subclinical fatty liver. Ten grams of silymarin (76% pure extract consisting in flavonolignans, taxifolin, and other trace compounds) per day, was administered as a water suspension by an oral drench to 15 cows from d 10 before expected calving to 15 d after calving. Milk production was measured, and colostrum, milk, and blood samples were analyzed during the experimental period. Treated animals showed the peak of milk production at 55 +/- 1.85 d after calving, 1 wk before the control group (62 +/- 3.27 d); the average peak production was 41.6 +/- 1.05 kg for the treated group vs. 39.1 +/- 1.44 kg for the control; the treated animals maintained a greater milk production than control cows throughout lactation (9922.1 +/- 215.7 vs. 9597.8 +/- 225.4 kg). Milk composition was unaffected by treatment. No silymarin residues were detected in colostrum and all milk samples. After calving, body condition score (BCS) decrease was greater for control compared with treated cows. Glucose, urea, triglycerides (TG), total cholesterol, beta-hydroxibutyrate (BHBA), and gamma-glutamyl transferase (GGT) in plasma were unaffected by treatment. Plasma nonesterified fatty acids (NEFA) on d-7 were higher in treated cows compared with the control group (741 vs. 181 micromol/L). From this evidence, it is possible to conclude that silymarin beneficially affected lactation performances and body condition of treated animals. Blood and milk parameters do not indicate any adverse effects of feeding this natural compound.