Jiří Špaček

The pathogenesis, diagnosis, and management of metastatic tumors to the ovary: a comprehensive review

Secondary tumors of the ovary account for 10–25% of all ovarian malignancies. The most common tumors that give rise to ovarian metastases include breast, colorectal, endometrial, stomach, and appendix cancer. The correct diagnosis of secondary ovarian tumors may be challenging as they are not infrequently misdiagnosed as primary ovarian cancer, particularly in the case of mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extra-ovarian metastases and, furthermore, may suggest the primary tumor site. Despite extensive study, some cases remain equivocal even after assessing a broad spectrum of antigens. Therefore, gene expression profiling represents an approach able to further discriminate equivocal findings, and one that has been proven effective in determining the origin of cancer of unknown primary site. The available data concerning secondary ovarian tumors is rather limited owing to the relative heterogeneity of this group and the practical absence of any prospective trials. However, several intriguing questions are encountered in daily practice, including rational diagnostic workup, the role of cytoreductive surgery, and consequent adjuvant chemotherapy. This review seeks to address these issues comprehensively and summarize current knowledge on the epidemiology, pathogenesis, and management of secondary ovarian tumors, including further discussion on the different pathways of metastatisation, metastatic organotropism, and their possible molecular mechanisms.

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer.

The purpose of our study was to evaluate a possible correlation between genetic polymorphisms in ATM and TGFB1 genes and late toxicity of chemoradiotherapy for locally advanced cervical cancer. Fifty five patients with FIGO stage IIB and higher without a disease recurrence with a mean follow up of 6 years were included. Late toxicity was assessed by EORTC/RTOG late toxicity criteria. Univariate and multivariate logistic regression model was used for statistical analysis. Degree of association between polymorphisms and late toxicity of chemotherapy was assessed on the basis of phi-coefficient (φ) as well. We did not find any association between 5557G>A polymorphism in the ATM gene or single TGFB1 polymorphisms and late toxicity. TGFB1 compound homozygosity (-1552delAGG, -509C>T, L10P) was a significant predictive factor of grade III-IV and any grade of complications in both univariate and multivariate logistic regression analyses and statistical significance of association between polymorphisms and late toxicity of chemoradiotherapy was confirmed also by the evaluation of phi-coefficient (φ). We conclude that haplotypes instead of single nucleotide polymorphic sites in the genes may better characterize the individual radiosensitivity. Keywords: cervical cancer, radiotherapy, ATM, TGFB1, late toxicity.

Healthcare‐associated infections in gynecology and obstetrics at a university hospital in the Czech Republic

To determine the spectrum of etiology and the incidence of healthcare‐associated infections (HAIs) among gynecologic and obstetric patients.

Hypersensitivity to chemoradiation in FANCA carrier with cervical carcinoma-A case report and review of the literature.

OBJECTIVE Compared to Fanconi anemia (FA) patients with homozygous defective two-alleles inheritance, there is a scarce or no evidence on one defective allele FANCA carriers, with respect to their cancer incidence, clinical and in vitro radiosensitivity and chemosensitivity. On that account, we report a case of a 30-year old FANCA mutation carrier woman with uterine cervix adenocarcinoma who was treated with chemoradiotherapy, in which unexpected acute toxicity and fatal late morbidity occured. METHODS We also report the results of an in vitro test for radiosensitivity, immunohistochemical examination with FANCA staining and human papillomavirus genotypization, and a review of the literature for FA carrier patients with respect to cancer incidence, clinical and in vitro response to chemo/radiotherapy, options of early heterozygosity detection, and methods of in vitro prediction of hypersensitivity to oncologic treatment. CONCLUSION Although there are no standard guidelines for management of FA carriers with malignancies and reports about chemo- or radiosensitivity in this population are scarce; patients with FA-A heterozygosity may have a high rate of complications from chemo/radiotherapy. Up to now, an optimum method for the prediction of radiosensitivity and the best parameter has not been found. Clinical radioresponsiveness is unpredictable in FA carriers and there is a pressing need of new rapid and predictive in vitro assays of radiation responses. Until then, the treatment of FA carriers with malignancies should be individualized, with respect to potential hypersensitivity to ionizing radiation or cross-linking agents.

Comparison of two long-term gestagen regimens in the management of recurrent vulvovaginal candidiasis: A pilot study

Vulvovaginal candidiasis (VVC) is a hormonal‐dependent infection but in contrast to sporadic VVC, therapy of recurrent vulvovaginal candidiasis (RVVC) is still unsolved. Long‐term administration of medroxyprogesterone acetate was evaluated for the management of RVVC. Overall, 20 patients were treated with Depo‐Provera; 14 patients were treated with Provera. Gestagen therapy was evaluated based on visual analogue scale (VAS), the frequency of attacks, the side effects of gestagens and the consumption of antifungals. There was a reduced symptomatology in both of the groups and substantial reduction in antifungal drug consumption during the second year of gestagen use. Twenty‐four patients (70.6%) evaluated their condition regarding the vulvovaginal area as improvement (VAS decrease of 3‐5 points). Five patients (14.7%) mentioned minimal or no improvement. Further, a number of antifungal drug‐treated episodes dropped dramatically during the study period. Both regimes provided similar results, but five patients from the Depo‐Provera group had to withdraw from gestagen therapy. Gestagen supplementation ameliorated the quality of life for the majority of patients with RVVC and suggested a potential role in the management of this syndrome, even if beneficial effect was evident after longer application, and some patients met with side effects that led to an interruption of therapy.

Expression of ATP-binding Cassette Proteins Pgp, MRP1, and MRP3 in Malignant and Benign Ovarian Lesions

BACKGROUND This study was designed to compare the expression of PgP (P-glycoprotein), MRP1 (multidrug related protein), and MRP3 in ovarian cancer patients, patients with benign ovarian tumors, and healthy women, and to evaluate the correlation between the expression of ATP-binding cassette proteins Pgp, MRP1, and MRP3 with stage, grade, and histological type. PATIENTS AND METHODS Tissue specimens from 212 women who underwent surgery at the Department of Obstetrics and Gynecology at University Hospital Hradec Králové were subjected to immunohistochemical staining for Pgp, MRP1, and MRP3. RESULTS The expression of Pgp and MRP1 was higher in ovarian tumor cells than in the cells lining the ovarian cyst. The lowest level of expression was found in normal ovarian tissue (p < 0.001). Histological subtype of epithelial ovarian cancer correlated with the expression of PgP, MRP1, and MRP3. The lowest level of Pgp and MRP1 expression was found in endometrioid ovarian cancers (p = 0.151; p = 0.013). Patients with advanced ovarian cancer (FIGO III + IV) had higher MRP1 expression than those with early stage ovarian cancer (median MRP1 FIGO I + II 80%; CI 60-100; FIGO III + IV 100%; CI 90-100; p = 0.100). An association was observed between MRP1 and tumor grade (p < 0.001). CONCLUSION Pgp and MRP1 expression was higher in ovarian tumor cells than in cells lining the ovarian cyst. The lowest level of expression was found in normal ovarian tissue. ATP-binding cassette proteins play an important role in ovarian cancer pathogenesis.Key words: ATP-binding cassette proteins - ovarian cancer - P-glycoprotein (Pgp) - multidrug related protein 1 (MRP1) - multidrug related protein 3 (MRP3) - drug resistanceThis work was supported by the Czech Ministry of Health NT 14107-3/2013.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 9. 11. 2015Accepted: 30. 8. 2016.