Comorbidity of Urogynecological and Gastrointestinal Disorders in Female Patients With Lichen Sclerosus.

OBJECTIVE: Lichen sclerosus (LS) is a chronic inflammatory disease with a significant impact on quality of life. The aim of this cross-sectional case-control study was to characterize concomitant urogynecological and gastrointestinal disorders in female patients with LS. METHODS: A medical records search between 2004 and 2012 yielded 455 women and girls (mean age 64 years) with LS. The study cohort was compared with a 10-fold age- and sex-matched control cohort. Gynecological cancers and their precursors; gynecological, urinary, and gastrointestinal disorders; and pain syndromes were evaluated. RESULTS: The well-known association between LS and increased risk of vulvar cancer and its precursors was also found in our study (relative risk [RR] = 100.0; p < .001 and high-grade squamous intraepithelial lesions RR = 110.0; p < .001, respectively), but we also found an increased risk for cervical cancer (RR = 6.0; p = .005) and endometrial cancer (RR = 2.9; p < .001). Gynecological pain syndromes such as dyspareunia (RR = 20.0; p < .001) and interstitial cystitis (RR = 5.0; p < .001) and urinary incontinence (RR = 4.8; p < .001) were also increased. Among gastrointestinal disorders, we found increased risk for celiac disease (RR = 6.8; p < .001), diverticular intestine diseases (RR = 1.9; p < .001), functional intestinal disorders (RR = 2.3; p = .003), and anal and rectal fissures (RR = 2.4; p = .046). CONCLUSIONS: We found that female patients with LS have an increased risk for gynecological cancers as well as for several urogynecological and gastrointestinal disorders. Increased awareness is required to identify and treat these concomitant disorders.

Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer.

PURPOSE OF THE REPORT: The aim of this study was to evaluate the distribution of hypoxia using 18F-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this 18F-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1α, CAIX, and GLUT1. PATIENTS AND METHODS: Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1-IIIC2r) were imaged with dual tracers 18F-EF5 and 18F-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129-135). 18F-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These 18F-EF5 hypoxic parameters were correlated with the size and localization of tumors in 18F-FDG PET/MRI and the results of hypoxia immunohistochemistry. RESULTS: All primary tumors were clearly 18F-FDG and 18F-EF5 PET positive and heterogeneously hypoxic with multiple 18F-EF5-avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters 18F-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in 18F-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1α and CAIX in tumor fresh biopsies. CONCLUSIONS: The 18F-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.

Decorin Expression in Human Vulva Carcinoma: Oncosuppressive Effect of Decorin cDNA Transduction on Carcinoma Cells.

The extracellular matrix proteoglycan decorin is well-known for its oncosuppressive activity. Here, decorin expression was examined in human vulva carcinoma tissue samples and in primary and commercial cell lines representing this malignant disease. Furthermore, the effect of adenovirus-mediated decorin cDNA (Ad-DCN) transduction on the viability, proliferation, and the expression and activity of the epidermal growth factor receptor (ErbB/HER) family members of the cell lines were investigated. Using in situ hybridization and immunohistochemistry for decorin, it was demonstrated that malignant cells in human vulva carcinoma tissues lack decorin expression. This result was true independently on tumor stage, grade or human papillomavirus status. RT-qPCR analyses showed that the human vulva carcinoma cell lines used in this study were also negative for decorin expression. Transduction of the cell lines with Ad-DCN caused a marked reduction in cell viability, while the proliferation of the cells was not affected. Experiments examining potential mechanisms behind the oncosuppressive effect of Ad-DCN transduction revealed that ErbB2/HER2 expression and activity in carcinoma cells were markedly downregulated. In conclusion, the results of this study showed that human vulva carcinoma cells lack decorin expression, and that Ad-DCN transduction of these cells induces oncosuppressive activity in part via downregulation of ErbB2/HER2.