Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression.

High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer and is among the most fatal gynecological malignancies worldwide, due to late diagnosis at advanced stages and frequent therapy resistance. In 47 HGSC patients, we assessed somatic and germline genetic variability of a custom panel of 144 known or suspected HGSC-related genes by high-coverage targeted DNA sequencing to identify the genetic determinants associated with resistance to platinum-based therapy. In the germline, the most mutated genes were DNAH14 (17%), RAD51B (17%), CFTR (13%), BRCA1 (11%), and RAD51 (11%). Somatically, the most mutated gene was TP53 (98%), followed by CSMD1/2/3 (19/19/36%), and CFTR (23%). Results were compared with those from whole exome sequencing of a similar set of 35 HGSC patients. Somatic variants in TP53 were also validated using GENIE data of 1287 HGSC samples. Our approach showed increased prevalence of high impact somatic and germline mutations, especially those affecting splice sites of TP53, compared to validation datasets. Furthermore, nonsense TP53 somatic mutations were negatively associated with patient survival. Elevated TP53 transcript levels were associated with platinum resistance and presence of TP53 missense mutations, while decreased TP53 levels were found in tumors carrying mutations with predicted high impact, which was confirmed in The Cancer Genome Atlas data (n = 260). Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes.

Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.

OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

History and current trends in the treatment of idiopathic overactive bladder.

OBJECTIVE: Historical and current view on the therapy of overactive bladder. METHODS: This review summarizes the historical approach and current therapy of overactive bladder. The articles were gathered from Pubmed and Scopus databases. Studies published before December 2020 were used for the review. RESULTS AND CONCLUSION: Overactive bladder is a condition that quite a lot reduces the quality of life of our patients. Our therapeutic approach starts with non-pharmacological treatment, such as pelvic floor exercises. The next step is a pharmacological approach. The entry level drug is trospium. If the effect is not sufficient, propiverine, solifenacin, fesoterodine, darifenacin or mirabegron are used. Electrostimulation or botulinum toxin A application is an option only in cases that didnt respond to pharmacological treatment. It is safe to say, that in the end, there is a way of reducing the severity of overactive bladder symptoms for every  patient.

Treatment options for locally recurrent vulvar cancer.

OBJECTIVE: Summarizing of treatment options for locally recurrent vulvar cancer in patients after previous complex oncological treatment and presenting a case report from our department. METHODS: Presenting a case report of a patient after previous complex oncological treatment for spinocellular cancer of the vulva who presented with a locally recurrent tumor. The patient was treated with a wide radical local excision of the tumor followed by a posterior thigh flap graft. CONCLUSION: Surgical intervention is the primary mode of treatment in locally recurrent cancers of the vulva. Wide radical local excision as a mode of treatment can be optimized by the use of grafts aiding in wound healing.

Antibiotic administration reduces the rate of intraamniotic inflammation in preterm prelabor rupture of the membranes.

BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

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.

Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial.

BACKGROUND: The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer. METHODS: In this randomised, open-label, phase 2 study, adult patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1-10 of each 21-day cycle) plus paclitaxel (175 mg/m(2), administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m(2) on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with ClinicalTrials.gov, number NCT01081951, and has been completed. FINDINGS: Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12.2 months [95% CI 9.7-15.0]) than in the chemotherapy alone group (median 9.6 months [95% CI 9.1-9.7) (HR 0.51 [95% CI 0.34-0.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.08-0.55]; p=0.0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. INTERPRETATION: Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA-mutated patients, and had an acceptable and manageable tolerability profile. FUNDING: AstraZeneca.

Clinical significance of the resistance proteins LRP, Pgp, MRP1, MRP3, and MRP5 in epithelial ovarian cancer.

OBJECTIVE: This study aimed to evaluate the correlation between the expressions of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and clinical outcome, and to determine the predictive and prognostic value of these transport proteins in patients with ovarian cancer. METHODS: Tumor samples from 111 chemonaive patients with epithelial ovarian cancer who underwent primary surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1, MRP3, and MRP5 expressions. RESULTS: MRP1 expression was greater among patients with late disease than among patients with early stage ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6% (confidence interval, 60-100); FIGO III + IV, 83.6% (confidence interval, 100-100); P = 0.03]. The histological subtype correlated with the expressions of LRP, Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more often among patients with higher Pgp and MRP1 than among patients with lower Pgp and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong Pgp expression, and strong MRP1 expression correlated significantly with shorter progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P = 0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking efficiency, and strong MRP1 expression correlated with poor patient survival (log-rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively). CONCLUSIONS: Pgp and MRP1 expressions were clinically significant in patients with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less important as a predictive and prognostic factor than MRP1 expression. MRP5 and LRP expressions were not applicable prognostic parameters regarding ovarian cancer.

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.

Importance of promoter methylation of GATA4 and TP53 genes in endometrioid carcinoma of endometrium.

BACKGROUND: Epigenetic changes are considered to be a frequent event during tumor development. Various methylation changes have been identified and show promise as potential cancer biomarkers. The aim of this study was to investigate promoter methylation of GATA4 and TP53 genes in endometrioid carcinoma of endometrium. METHODS: To search for promoter methylation of GATA4 and TP53 genes we used methylation-specific PCR (MSP) to compare the methylation status of 54 patients with endometrioid carcinoma of endometrium and 18 patients with normal endometrial tissue. RESULTS: In our study MSP revealed GATA4 promoter methylation in 44 of 54 in the carcinoma group (81.5%), and in none of the control group. No methylation was observed in TP53 gene. CONCLUSIONS: In conclusion, our study showed that there is significantly higher methylation in GATA4 gene in the endometrial cancer group compared with samples of non-neoplastic endometrium. The finding suggests the importance of hypermethylation of this gene in endometrial carcinogenesis and could have implications for future diagnostic and therapeutic strategies for endometrial cancer based on epigenetic changes.

DNA methylation of selected tumor suppressor genes in endometrial hyperplasia.

AIMS: To investigate DNA methylation of specific gene promoters in endometrial hyperplasia compared to normal endometrial tissue. MATERIALS AND METHODS: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 64 tissue samples with atypical endometrial hyperplasia, 60 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with normal endometrium. RESULTS: Differences in DNA methylation among the groups were found in PTEN, CDH13, and MSH6 promoters (PTEN: atypical hyperplasia 32%, benign hyperplasia 6.8%, normal endometrium 10%; P=0.004; CDH13: atypical hyperplasia, 50%; benign hyperplasia, 43%; normal endometrium 8.1%; P=0.003; MSH6 atypical hyperplasia 84%, benign hyperplasia, 62%; normal endometrium, 52%; P=0.008.) Higher rates of CDH13 promoter methylation were identified in the groups with both forms of endometrial hyperplasia when compared to the control group (atypical hyperplasia, P=0.003, benign hyperplasia, P=0.0002). A higher rate of DNA methylation of the PTEN and MSH6 promoters was observed in samples with atypical endometrial hyperplasia than in samples with benign endometrial hyperplasia (PTEN: P=0.02; MSH6: P=0.01) and samples with normal endometrial tissue (PTEN, P=0.04; MSH6, P=0.006). CONCLUSION: DNA methylation of CDH13, PTEN, and MSH6 appear to be involved in the development of endometrial hyperplasia.

Radiofrequency therapy for severe idiopathic vulvodynia.

OBJECTIVE: The study aimed to provide a description of a new and a hopeful possibility in the treatment of severe vulvodynia, which does not respond to treatments used so far. MATERIALS AND METHODS: The use of radiofrequency therapy in vulvodynia treatment is described for the first time. This method was suggested by a neurosurgeon after applying all available possibilities. RESULT: In this article, we are reporting on the successful use of the pulsed radiofrequency treatment in a patient with intractable chronic vulvodynia. CONCLUSIONS: To our knowledge, this is the first report of a successful use of pulsed radiofrequency in the treatment of chronic vulvodynia. If efficacy of pulsed radiofrequency is confirmed by more studies, it would be a welcome addition to the treatment modalities used to treat this sometimes truly intractable condition.

Pyelovesicostomy as an Alternative Surgical Treatment for Complex Ureteral Lesions After Kidney Transplant.

OBJECTIVES: We evaluated the feasibility, safety, and long-term outcomes of pyelovesicostomy as an alternative surgical treatment for complex ureteral lesions after kidney transplant. MATERIALS AND METHODS: A single-center, retrospective, observational cohort study was conducted on 5 adult kidney transplant recipients who underwent pyelovesicostomy between January 2000 and June 2023. The collected data included patient demographics, surgery indication, time from transplant to pyelovesicostomy, procedure details, and kidney function at various time points after surgery. Primary outcomes were allograft function and complications. RESULTS: The 5 patients (4 female, 1 male) had a mean age of 65.8 years and mean body mass index of 26.8. Indications were complex ureteral lesions. The time between transplant and reoperation ranged from 4 days to 12 years. Renal function improved for all patients, with a progressive decrease in mean serum creatinine concentration. The mean follow-up period extended to 7 years. One patient died with the graft still functional at 20 years after the operation, whereas the remaining 4 patients continue to live with functional grafts. CONCLUSIONS: Our study suggests that pyelovesicostomy may provide a potent alternative for the management of complex ureteral lesions after kidney transplant. We have observed good short-term and long-term outcomes in specific patients, pointing toward a promising avenue oftreatment worth further exploration. This reaffirms the importance of a personalized approach in medicine, to consider each patient's unique conditions and characteristics during therapeutic decisions.

A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.

AIMS: To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). METHODS: This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. RESULTS: Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. CONCLUSION: Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].

Is there an association between pelvic organ prolapse and oxidative stress? A systematic review.

INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) has not been fully elucidated, although accumulating evidence suggests that oxidative stress is involved. The present systematic review comprehensively discusses this topic. METHODS: The PubMed/Medline, Scopus, and Web of Science databases were searched for relevant studies published up to May 2021. This systematic review was registered in the PROSPERO database (registration number CRD42021242240). Two independent researchers screened and selected articles that fulfilled predefined inclusion criteria, performed a quality assessment, and extracted the relevant data. Of 901 original articles retrieved, 8 fulfilled the selection criteria and were included in the review. RESULTS: Elevated levels of markers of oxidative stress, such as advanced glycation end products, hydroxynonenal and hydroxydeoxyguanosine, were found in various parts of the pelvic floor of patients with POP. Accordingly, the levels of glutathione peroxidase and superoxide dismutase, known as major antioxidant enzymes, were reduced, compared to those in healthy controls. Levels of two other markers (mitofusin 2 and nuclear factor erythroid derived 2) also support hypotheses suggesting the involvement of oxidative stress in POP. CONCLUSIONS: In the literature available, an association between oxidative stress and pelvic organ prolapse was confirmed.

High-Dose-Rate Brachytherapy as an Organ-Sparing Treatment for Early Penile Cancer.

BACKGROUND: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. METHODS: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. RESULTS: The median follow-up was 117.5 months (range, 5-210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7-97.7%) and 68.3% (95% CI: 44.0-92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45-97.7%) and 62.1% (95% CI: 34.8-89.4%), respectively. CONCLUSIONS: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort-the second largest reported to date in this clinical setting-prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer.

Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2. METHODS: Patients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients' CD14+ monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1. RESULTS: Between November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events). CONCLUSIONS: DCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC. TRIAL REGISTRATION NUMBER: NCT02107937, EudraCT2010-021462-30.

[Pitfalls of the current laboratory diagnosis and treatment of vulvovaginal candidiasis]. / Úskalí soucasné laboratorní diagnostiky a terapie vulvovaginální kandidózy.

Vulvovaginal candidiasis remains one of the most frequently diagnosed inflammatory diseases of the vagina, which affects most sexually active women. In most patients, it is manifested as acute inflammation which is easy to diagnose and treat. However, in the susceptible population, it may be characterized by recurrent episodes, usually with an unknown cause or exacerbating moment. These facts complicate the diagnosis and therapy. This is highlighted by both non-specific symptoms shared with many other vaginal infections and paucity of reliable signs for diagnosis. Under these circumstances, it is difficult to associate vaginal complaints with yeasts and, vice versa, the presence of yeasts does not necessarily confirm fungal aetiology. Therefore, it is better to regard the condition as a syndrome and the chronic problems as vulvovaginal discomfort. It is a prerequisite for an unbiased diagnostic approach, increasing the probability of finding the real cause of the problem and the chances of treating or even curing the disease. The article is concerned with controversial and problematic aspects of diagnosis and treatment of vulvovaginal candidiasis with a focus on laboratory diagnosis, terminology, epidemiology and ecology of yeasts in relation to vaginal microbiota and, last but not least, on alternative therapeutic approaches.

Non-closure of peritoneum after abdominal hysterectomy for uterine carcinoma does not increase late intestinal radiation morbidity.

BACKGROUND/AIM: To evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity. MATERIALS AND METHODS: A total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed. RESULTS: Visceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm(3) (range 200-840 cm(3), median 469 cm(3)); mean volume of bowels irradiated in patients without peritonealization was 456 cm(3) (range 254-869 cm(3), median 428 cm(3)). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34). CONCLUSION: Non-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.

Long-term experience with percutaneous biopsies of pelvic lesions using CT guidance.

To evaluate the accuracy, efficiency, complication rate, technical features, and relations among followed parameters of CT-guided percutaneous biopsies of the pelvic lesions. 140 biopsies in 136 patients for tumors, sizes 17-160 mm in largest diameter, were carried out in patients with probable tumorous pelvic process within ten years period. The patients were women in 77 cases and men in 59 cases, aged 21 to 87 years. The lesions´ size varied from 17 mm to 160 mm in largest diameter. In 135 biopsies (96.4%) results were true positive or true negative; only 5 procedures (3.6%) were histologically false negative and had to be verified surgically. Metastatic affection was the most common diagnosis (26.4%). Lymphomas were diagnosed in 25%; serous adenocarcinoma of ovary or uterine tube was verified in 15.7% of cases. Totally 7 complications (5%) were confirmed, all were minor hemorrhages. A statistically significant relation between the complication rate and hypervascular character (p = 0.00004), and between needle gauge and histological accuracy (p = 0.00429) was revealed. Core needle biopsy using percutaneous approach and CT guidance had a high overall accuracy in determining the final histological diagnosis including subtyping. Concurrently, the complication incidence was low.