INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to end-stage renal disease. In this study, we examine the indications, procedures, and outcomes of native nephrectomy (NN) in ADPKD patients at our transplant center. Drawing on 25 years of clinical practice, we aim to provide insights into the surgical management of ADPKD, focusing on the specific factors influencing NN. MATERIALS AND METHODS: A retrospective study was conducted involving ADPKD patients who underwent KT and NN between 1999 and 2023. Collected data encompassed demographics and surgery parameters, such as duration, hospital stay length, blood loss, and complications. Patients were classified based on the urgency (acute/planned) of the NN and its type (unilateral/bilateral), followed by an analysis of the outcomes per group. RESULTS: Out of 152 patients post-KT for ADPKD, 89 (58.6%) underwent NN. The procedures were predominantly unilateral (71; 64%), with bilateral NN accounting for 40 (36%) cases. NN timing relative to KT was 31 (27.9%) pretransplant, 9 (8.1%) concomitant, 51 (45.9%) posttransplant, and 10 (9%) patients undergoing the sandwich technique. Acute NN were performed in 42 cases, while 69 were planned. Acute NNs were associated with longer surgeries, greater blood loss, and a higher incidence of perioperative complications compared to planned NNs. Specifically, unilateral acute NN had a 23.8% complication rate compared to 2.9% in planned cases; bilateral acute NN showed a 28.6% complication rate versus 4.3% in planned cases. CONCLUSION: This investigation accentuates the significance of planning and selection in NN for ADPKD, factoring in the heightened risk of complications. Acute NN are linked to worse outcomes, including higher rates of complications. The data emphasize the necessity of tailored surgical approaches based on individual patient circumstances.

• Klíčová slova
• ADPKD, Autosomal dominant polycystic kidney disease, Kidney transplantation, Native nephrectomy,
• MeSH
• časové faktory MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nefrektomie * metody   MeSH
• polycystické ledviny autozomálně dominantní * chirurgie   MeSH
• pooperační komplikace epidemiologie   etiologie   MeSH
• retrospektivní studie MeSH
• transplantace ledvin * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To investigate DNA methylation of specific tumor suppressor genes in endometrial hyperplasia compared to normal endometrial tissue. File and methodology: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 40 tissue samples with atypical endometrial hyperplasia, 40 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with a normal endometrium. RESULTS AND CONCLUSION: Differences in DNA methylation among the groups were found in TWIST1, GATA4, MUS81, and NTRK1 genes (TWIST1: atypical hyperplasia 67.5%, benign hyperplasia 2.5%, normal endometrium 22.5%; P < 0.00001; GATA4: atypical hyperplasia 95%, benign hyperplasia 65%, normal endometrium 22.5%; P < 0.00001; MUS81: atypical hyperplasia 57.5%, benign hyperplasia 22.5%, normal endometrium 5%; P < 0.00001; NTRK1: atypical hyperplasia 65%, benign hyperplasia 27.5%, normal endometrium 10%; P < 0.00001). Higher methylation rates were observed for the tumor suppressor genes of TWIST1, GATA4, MUS81, and NTRK1 in samples with atypical endometrial hyperplasia compared to samples with normal endometrial tissue, and higher methylation rates were found in samples with atypical endometrial hyperplasia compared to samples of benign endometrial hyperplasia. DNA methylation of TWIST1, GATA4, MUS81, and NTRK1 is involved in the pathogenesis of atypical endometrial hyperplasia.

• Klíčová slova
• Epigenetics, GATA4, MUS81, Methylation, NTRK1, TWIST1, curettage, endometrial hyperplasia,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• endonukleasy genetika   MeSH
• hyperplazie endometria * genetika   patologie   metabolismus   MeSH
• jaderné proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• receptor trkA * genetika   MeSH
• transkripční faktor GATA4 * genetika   metabolismus   MeSH
• transkripční faktor Twist * genetika   MeSH
• tumor supresorové geny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• endonukleasy MeSH
• GATA4 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• MUS81 protein, human MeSH Prohlížeč
• NTRK1 protein, human MeSH Prohlížeč
• receptor trkA * MeSH
• transkripční faktor GATA4 * MeSH
• transkripční faktor Twist * MeSH
• TWIST1 protein, human MeSH Prohlížeč

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.

• Klíčová slova
• TP53, biomarkers, ovarian carcinoma, platinum resistance, treatment response,
• MeSH
• chemorezistence * genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorový supresorový protein p53 * genetika   MeSH
• nádory vaječníků * genetika   farmakoterapie   patologie   MeSH
• platina terapeutické užití   farmakologie   MeSH
• regulace genové exprese u nádorů MeSH
• sekvenování exomu metody   MeSH
• senioři MeSH
• serózní cystadenokarcinom * genetika   farmakoterapie   patologie   MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorový supresorový protein p53 * MeSH
• platina MeSH
• TP53 protein, human MeSH Prohlížeč

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.

• Klíčová slova
• CDH13, MSH6, PTEN, endometrial hyperplasia, epigenetics, methylation,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• hyperplazie endometria * genetika   patologie   MeSH
• hyperplazie genetika   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• nádory endometria * genetika   patologie   MeSH
• tumor supresorové geny MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH

AIM: A retrospective audit from a urological center focused on urological fistulas that directly connect with the treatment of gynecological malignancy. Ureteroarterial fistulas, i.e., pathological communication between the ureter and the artery, are discussed in more detail. MATERIALS AND METHODS: Over a period of ten years, from 2011 to 2020, a group of 47 patients with a diagnosis of urinary fistula was retrospectively evaluated. These patients, with a history of treatment for gynecological malignancy, were sent to our clinic from local and non-regional departments in the Czech Republic. We found three cases of ureteroarterial fistula in the presented analysis that focused on urological toxicity of oncogynecological treatment. RESULTS: Within the mentioned period of ten years, we recorded 64 cases of urinary fistulas, and 47 patients (73.4%) were directly related to oncogynecological treatment. In the group with gynecological tumors, we found three patients (6.4%) with a diagnosis of ureteroarterial fistula, two of whom died directly related to this complication (exsanguination). These patients were treated for cervical cancer. All of them underwent radiotherapy during the treatment. CONCLUSION: Ureteroarterial fistulas are the most severe complications that can occur in medicine. This work confirms that we have encountered these cases even recently. Management is highly demanding for patients affected in this way and requires multidisciplinary cooperation. Endovascular intervention methods can control bleeding in emergency situations with non-surgical approaches. However, they are usually the first step towards a definitive surgical solution.

• Klíčová slova
• artery, fistula, hematuria, malignancy, ureter,
• MeSH
• cévní píštěle * etiologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• močové píštěle * etiologie   MeSH
• nádory děložního čípku MeSH
• nádory ženských pohlavních orgánů radioterapie   MeSH
• nemoci močovodu etiologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

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.

• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace ledvin * škodlivé účinky   metody   MeSH
• ureter * chirurgie   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

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.

• Klíčová slova
• HDR brachytherapy, penile carcinoma,
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• lidé MeSH
• oxidační stres MeSH
• pánevní dno MeSH
• prolaps pánevních orgánů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

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.

• Klíčová slova
• clinical trials, dendritic cells, immunotherapy, phase II as topic,
• MeSH
• acetylcystein analogy a deriváty   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom farmakoterapie   MeSH
• imunoterapie metody   MeSH
• karboplatina farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši MeSH
• paclitaxel farmakologie   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myši MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• acetylcystein MeSH
• karboplatina MeSH
• paclitaxel MeSH
• S-1,2-dichlorovinyl-N-acetylcysteine MeSH Prohlížeč

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.

• Klíčová slova
• CT guidance, Pelvic tumor, complication rate, core needle biopsy, diagnostic accuracy, percutaneous approach,
• MeSH
• biopsie dutou jehlou metody   MeSH
• lidé MeSH
• pánev * diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie metody   MeSH
• retrospektivní studie MeSH
• ultrazvukem navigovaná biopsie * metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH