Impact on Radiological and Pathological Response with Neoadjuvant Chemoradiation and Its Effect on Survival in Squamous Cell Carcinoma of Thoracic Esophagus

Background

Neoadjuvant chemoradiation (NCRT) has been shown to improve survival in patients with locally advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the role of 18-FDG PET-CT in predicting pathological response to NCRT.

Material and Methods

We assessed 70 patients of esophageal SCC who underwent NCRT and were evaluated with baseline and post chemoradiation 18F-FDG PET-CT scan. Receiver operating characteristic (ROC) curve was generated by analyzing the sensitivity and specificity of different cut-off points for defining a positive test and their ability to predict pathological complete response. Univariate and multivariate analysis were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method.

Results

Radiological and pathological complete response was achieved in 44.3 % (n = 31) and 34.3 % (n = 24) patients, respectively. Using ROC curves, post-treatment standardized uptake value (SUV) max [3.25, area under curve (AUC) 0.752] and % change in SUVmax cut-off value (72.32 %, AUC 0.705) was used to predict pathological response. Significant associations between pathological response in primary tumor and post chemotherapy/radiotherapy SUVmax values (p = 0.016), % change in SUVmax (p = 0.006), radiological response in primary (p = 0.006), and grade of dysphagia at presentation (p = 0.041) were observed. Mean overall survival and relapse free survival was 83 and 58 %, respectively at 34 months.

Conclusion

18F-FDG PET-CT can be used to predict pathological response to NCRT in locally advanced SCC.

     

甲苯磺丁脲固体分散物的X线衍射研究

用X线衍射(XRD)对甲苯磺了脲(D860)与脲、聚乙烯吡咯烷酮(PVP)和聚乙烯二醇6000(PEG 6000)的固体分散物进行较详细的研究,并与它们的溶出速率进行关联。D860—PVP分散物为无定形态,溶出速率大。用熔融法制备的固体分散物中,D860在D860—脲,D860—PEG中为部分互溶,部分呈微晶析出,为过饱和状态,活性强,溶出速率快。而用溶剂法制备的D860—PEG近似物理混合状态,大部分以微晶形态分散,溶出速率较慢。陈化试验表明D860分散物在贮存期间无晶体结构变异,溶出速率的下降估计是由于药剂活性改变所致。     

Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol

Resveratrol, a phenolic substance present in grapes and a variety of medical plants, has been reported to induce vasorelaxation, however the mechanisms are uncertain. In this paper we investigate the possible participation of K(+) channels in the endothelium-independent vasodilatation of rat aorta induced by resveratrol. Resveratrol induced concentration-dependent relaxation of rings with endothelium and without endothelium. We used different potassium channel inhibitors to determine whether the K(+) channels mediated endothelium-independent relaxation of rat aorta induced by resveratrol. Highly selective blocker of ATP-sensitive K(+) channels, glibenclamide, as well as non-selective blockers of K(+) channels, tetraethylammonium, did not block resveratrol-induced relaxation of rat aortic rings. Charybdotoxin, a blocker of calcium-sensitive K(+) channels did not affect the resveratrol-induced relaxation. 4-Aminopiridine, non-selective blocker of voltage-gated K(+) (Kv) channels, and margatoxin that inhibits Kv1 channels abolished relaxation of rat aortic rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed rat aortic rings with denuded endothelium. It seems that 4-aminopiridine and margatoxin-sensitive K(+) channels located in the smooth muscle of rat aorta mediated this relaxation.     

The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is effective in treating intestinal adenomas in humans with Familial Adenomatous Polyposis (FAP) and in preventing intestinal tumors in the C57Bl/6J- Min+ (Min) mouse, an animal model of FAP. Sulindac is a prodrug metabolized by the liver and intestinal flora to a sulfone, which has no anti-inflammatory activity, and a sulfide, which is the active anti- inflammatory metabolite. In this study, we determined which of these metabolites is responsible for the anti-tumor effect of sulindac in Min mice. Min mice were treated with either sulindac sulfone or sulindac sulfide (0.5 +/- 0.1 mg/day). Min mice and homozygous C57Bl/6J-(+/+) normal litter-mates lacking the Apc mutation (+/+) were used as controls. At 110 days of age, all mice were euthanized and their intestinal tracts examined. Control Min mice had 33.2 +/- 6.6 tumors per mouse compared to 0.6 +/- 0.3 tumors for sulindac sulfide-treated Min mice (P < 0.001) and 21.9 +/- 4.5 tumors per mouse for sulindac sulfone-treated Min mice (P > 0.05). Decreased enterocyte apoptosis was observed in Min control mice and Min mice treated with sulindac sulfone. Sulindac sulfide restored to normal the level of apoptosis in the mucosa of Min animals and decreased levels of PGE2 in the small intestine of treated Min animals by 59% (P < 0.001). These data suggest that the anti-tumor effect of sulindac in Apc-deficient animals is mediated by the sulfide metabolite and correlates with suppression of tissue prostaglandin synthesis.      

The barium enema scout film: cost effectiveness and clinical efficacy

The authors prospectively evaluated 1,001 consecutive double-contrast barium enema examinations to determine the efficacy of the preliminary film. The scout films were evaluated for the presence of unsatisfactory amounts of residual feces and clinically significant extracolonic abnormalities. The contrast studies were independently evaluated in a double-blind manner for satisfactory colonic preparation as well as extracolonic abnormalities. The routine use of the scout film resulted in an increase in health care charges and departmental costs. In addition, there was no significant increase in the detection of extracolonic abnormalities. Our data suggest that routine use of scout films prior to contrast studies is unnecessary, although selective use in some clinical situations may be justified.