Efficacy of topical pale sulfonated shale oil in the treatment of venous leg ulcers: A randomized, controlled, multicenter study

BackgroundVenous leg ulcers are a growing socioeconomic burden. Pale sulfonated shale oils (PSSO) are used for therapy of inflammatory skin diseases and have been shown to enhance wound healing in vitro and in vivo. The aim of this study was to investigate whether PSSO is capable of enhancing venous ulcer healing beyond compression therapy alone.MethodsOne hundred nineteen patients were enrolled in this randomized, multicenter, observer-blind study. In the treatment group, PSSO 10% was applied daily for 20 weeks, and the control group received the vehicle only. Wounds were covered by a nonadherent gauze dressing, and compression therapy with short-stretch elastic bandages was performed in an outpatient setting. The primary study end point was defined as cumulative reduction in wound area; the secondary study end point was treatment success as assessed by both physicians and patients. Additionally, adverse events, including changes with respect to physical examination and vital signs, were documented.ResultsAt the end of the study period, ulcer size was significantly more reduced in the PSSO group compared with the vehicle group (15 ± 15.9 to 6.2 ± 12.9 cm2 vs 11.4 ± 14.5 to 10.8 ± 15.7 cm2; P = .0005). The cumulative relative reduction in ulcer area was significantly higher in the PSSO group (−4391 ± 4748.7 vs −231.9 ± 6283.6 % × days; P < .0001). Relative reduction in wound area was significantly greater in the PSSO group as early as 6 weeks after the beginning of treatment (−47.4 ± 28.4 vs −23.8 ± 42.2%; P < .001). PSSO was judged successful both by physicians and patients. There were no significant differences in adverse events (PSSO, 9 [12.2%]; vehicle, 7 [11.1%]. Similarly, tolerability of PSSO was equal to the tolerability of the vehicle.ConclusionPale sulfonated shale oils were capable of favoring venous ulcer healing in addition to compression therapy. PSSO should be considered for future wound care protocols for treatment of venous leg ulcers

Advanced thyroid carcinomas: neural network analysis of ultrasonographic characteristics

Background Ultrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain characteristics observable by ultrasound have recently been identified that may indicate malignancy. This retrospective cohort study was conducted to test the hypothesis that advanced thyroid carcinomas show distinctive clinical and sonographic characteristics. Using a neural network model as proof of concept, nine clinical/sonographic features served as input. Methods All 96 study enrollees had histologically confirmed thyroid carcinomas, categorized (n = 32, each) as follows: group 1, advanced carcinoma (ADV) marked by local invasion or distant metastasis; group 2, non-advanced papillary carcinoma (PTC); or group 3, non-advanced follicular carcinoma (FTC). Preoperative ultrasound profiles were obtained via standardized protocols. The neural network had nine input neurons and one hidden layer. Results Mean age and the number of male patients in group 1 were significantly higher compared with groups 2 (p = 0.005) or 3 (p <  0.001). On ultrasound, tumors of larger volume and irregular shape were observed significantly more often in group 1 compared with groups 2 (p <  0.001) or 3 (p ≤ 0.01). Network accuracy in discriminating advanced vs. non-advanced tumors was 84.4% (95% confidence interval [CI]: 75.5–91), with positive and negative predictive values of 87.1% (95% CI: 70.2–96.4) and 92.3% (95% CI: 83.0–97.5), respectively. Conclusions Our study has shown some evidence that advanced thyroid tumors demonstrate distinctive clinical and sonographic characteristics. Further prospective investigations with larger numbers of patients and multicenter design should be carried out to show whether a neural network incorporating these features may be an asset, helping to classify malignancies of the thyroid gland

DOG1 overexpression is associated with mismatch repair deficiency and BRAF mutations but unrelated to cancer progression in colorectal cancer

Introduction. The transmembrane channel protein DOG1 (Discovered on GIST1) is normally expressed in the gastrointestinal interstitial cells of Cajal and also in gastrointestinal stroma tumors arising from these cells. However, there is also evidence for a relevant role of DOG1 expression in colorectal cancers. This study was undertaken to search for associations between DOG1 expression and colon cancer phenotype and key molecular alterations. Methods. A tissue microarray containing samples from more than 1,800 colorectal cancer patients was analyzed by immunohistochemistry. Results. DOG1 immunostaining was detected in 503 (30.2%) of 1,666 analyzable colorectal cancers and considered weak in 360 (21.6%), moderate in 78 (4.7%), and strong in 65 (3.9%). Strong DOG1 immunostaining was associated with advanced pT stage (p=0.0367) and nodal metastases (p=0.0145) but these associations were not retained in subgroups of 1,135 mismatch repair proficient and 86 mismatch repair deficient tumors. DOG1 positivity was significantly linked to several molecular tumor features including mismatch repair deficiency (p=0.0034), BRAF mutations (p<0.0001), nuclear p53 accumulation (p=0.0157), and PD-L1 expression (p=0.0199) but unrelated to KRAS mutations and the density of tumor infiltrating CD8 positive lymphocytes. Conclusion. Elevated DOG1 expression is frequent in colorectal cancer and significantly linked to important molecular alterations. However, DOG1 overexpression is largely unrelated to histopathological parameters of cancer aggressiveness and may thus not serve as a prognostic parameter for this tumor entity

Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p &amp;lt; 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p &amp;lt; 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p &amp;lt; 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness