Functional Outcome and Safety of Endoscopic Treatment Options for Benign Prostatic Obstruction (BPO) in Patients ≥ 75 Years of Age.

Background: The selection of suitable patients for the surgical treatment of benign prostatic obstruction (BPO) is a challenge in persons ≥75 years of age. Methods: After a systematic literature search of PubMed, 22 articles were included in this review. Clinical and functional parameters were evaluated statistically. Results: The mean age of the patients was ≥79 years. The mean duration of postoperative catheterization ranged between 2 (d) (ThuLEP, thulium laser enucleation of the prostate) and 4.4 days (TURP, transurethral resection of the prostate). Complication rates ranged between 6% (HoLAP, holmium laser ablation of the prostate) and 34% (PVP, photoselective vaporization of the prostate); the maximum rate of severe complications was 4% (TURP). The mean postoperative maximal urinary flow (Qmax) in mL/sec. ranged between 12.9 mL/sec. (HoLAP) and 19.8 mL/sec (Hol-TUIP, holmium laser transurethral incision of the prostate). The mean quality of life (QoL) score fell from 4.7 ± 0.9 to 1.8 ± 0.7 (HoLEP), from 4.1 ± 0.4 to 1.9 ± 0.8 (PVP), from 5.1 ± 0.2 to 2.1 ± 0.2 (TURP), and from 4 to 1 (ThuVEP, thulium laser vapoenucleation of the prostate). Pearson's correlation coefficient (r) revealed a positive linear correlation between age and inferior functional outcome (higher postoperative International Prostate Symptom Score (IPSS) [r = 0.4175]), higher overall complication rates (r = 0.5432), and blood transfusions (r = 0.4474) across all surgical techniques. Conclusions: This meta-analysis provides the summary estimates for perioperative and postoperative functional outcome and safety of endoscopic treatment options for BPO in patients ≥ 75 years of age. Of particular importance is that all surgical techniques significantly improve the postoperative quality of life of patients in this age group compared to their preoperative quality of life.

Detection of Recurrence through microRNA-371a-3p Serum Levels in a Follow-up of Stage I Testicular Germ Cell Tumors in the DRKS-00019223 Study.

PURPOSE: Surveillance of clinical stage I (CSI) testicular germ cell tumors (GCT) is hampered by low sensitivity and specificity of current biomarkers for detecting relapses. This study evaluated if serum levels of microRNA371a-3p (M371 test) can: (i) Accurately detect relapses, (ii) detect relapses earlier than conventional technology, and (iii) if elevated postoperative M371 levels may predict relapse. EXPERIMENTAL DESIGN: In a multicentric setting, 258 patients with testicular CSI GCT were prospectively followed by surveillance for a median time of 18 months with serial measurements of serum M371 levels, in addition to standard diagnostic techniques. Diagnostic characteristics of M371 for detecting relapses were calculated using ROC curve analysis. RESULTS: Thirty-nine patients recurred (15.1%), all with elevated M371 levels; eight without relapse had elevations, too. The test revealed the following characteristics: area under the ROC curve of 0.993, sensitivity 100%, specificity 96.3%, positive predictive value 83%, negative predictive value 100%. Earlier relapse detection with the test was found in 28%, with non-significant median time gain to diagnosis. Postoperative M371 levels did not predict future relapse. CONCLUSIONS: The sensitivity and specificity of the M371 test for detecting relapses in CSI GCTs are much superior to those of conventional diagnostics. However, post-orchiectomy M371 levels are not predictive of relapse, and there is no significant earlier relapse detection with the test. In all, there is clear evidence for the utility of the M371 test for relapse detection suggesting it may soon be ready for implementation into routine follow-up schedules for patients with testicular GCT.

Effects of COVID-19 Infection on Spermatogenesis, Oxidative Stress and Erectile Function.

BACKGROUND: Our aim was to evaluate the effect of COVID-19 infection on male fertility and sexual function. METHODS: Thirty-one patients were investigated over a mean follow-up of 90 days (22-527) after a COVID-19 infection. Erectile dysfunction (ED), blood tests for sexual hormones, semen analysis including analysis of oxidative stress (OS), as well as COVID-19 antibody titer and the nasal COVID-19 PCR test were evaluated pre- and post-infection. RESULTS: Five patients reported a mild de novo ED (16.13%). One patient had a de novo positive mixed antiglobulin reaction test after the infection. We found no significant difference between pre-COVID-19 and post-COVID-19 spermiogram parameters (p = 0.815). OS showed no significant association with COVID-19 infection, but with pathological spermiogram categories, sperm concentration, total sperm count, testis volume, FSH and testosterone. CONCLUSION: COVID-19 infection does not appear to affect sperm quality and OS negatively in the intermediate term. Further investigations will be needed to assess the potential long-term effects of the infection and vaccination on male sexual function and fertility.

Renal Arteriovenous (AV) Fistula after High-Grade Blunt Renal Trauma Caused by Traffic Accidents.

PURPOSE: To report a series of three patients with traumatic renal AV fistulas after blunt renal laceration. METHODS: We retrospectively analyzed the renal trauma cases treated in the Department of Urology of Salzburg University Clinic during a time period of 10 years concerning traumatic AV fistula formation and other clinical parameters. RESULTS: In total, 3 cases of traumatic AV fistula formation were identified in 106 blunt renal trauma patients (2.8%), with a mean age of 39 (17-56) years. All renal traumas were classified as American Association for the Surgery of Trauma (AAST) grade IV. Two patients were primarily treated with ureteral stent; one was managed conservatively. All AV fistulas were diagnosed after a mean time of 7 (1-13) days. Two patients were symptomatic with gross hematuria, and the mean time between trauma and onset of symptoms was 11 (9-13) days. All cases were managed via coil embolization after a mean of 10 (8-13) days. Two patients received a second intervention after a mean of 18 (11-25) days. The mean AV fistula size was 18.7 (12-24) mm. Mean hemoglobin loss was 3.6 g/dL. One patient received one erythrocyte concentrate. Discharge was after a mean time of 13.3 (7-12) days, with the mean time of intensive care treatment being 2.3 (1-3) days. CONCLUSIONS: Traumatic renal AV fistula is a rare but severe complication associated with higher-grade renal trauma. It can become evident through hematuria or blood loss several days after the initial trauma. The availability of coil embolization in a trauma center can help kidney preservation management.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Isochromosome 12p Formation Regulates Vitamin D Metabolism in Testicular Cancer.

Isochromosome 12p (iChr12p) is typical in almost all invasive testicular cancers. Increased copy number of genes on 12p is associated with the development of a clinically manifest tumor; however, the causative genes have not yet been identified. Chromosome 12 harbors many genes involved in Vitamin D metabolism. RNAseq analysis of Vitamin D receptor (VDR) genes from the TCGA cohort revealed that clustering of VDR expression signatures could differentiate between pure seminomas and non-seminomatous germ cell tumors (NSGCT). Using TCGA mRNA expression of anabolic (CYP2R1, CYP27A1 and CYP27B1) and catabolic (CYP24A1) Vitamin D enzymes, positive (PTHLH, IFNG, and TNF) and negative (FGF23) feedback regulators could also clearly distinguish between pure seminomas and NSGCT. We hypothesize that the regulation of Vitamin D metabolism might be disturbed through iChr12p formation, influencing testicular carcinogenesis via increased FGF23 and PTHLH expression. While FGF23 represses CYP27B1 and activates catabolism of active hormone, increased PTHLH secretion can lead to hypercalcemia via inactivation of VDR. In conclusion, testicular cancer is associated with extensive modifications in intratesticular Vitamin D homeostasis. Further research is needed to clarify whether Vitamin D deficiency causes the formation of iChr12p and whether Vitamin D deficiency via iChr12p genomic aberration is involved in testicular carcinogenesis.

The Antimicrobial Resistance (AMR) Rates of Uropathogens in a Rural Western African Area-A Retrospective Single-Center Study from Kpando, Ghana.

Little is known about the antimicrobial resistance (AMR) status of uropathogens in Western Africa. We performed a retrospective evaluation of urine cultures collected from the rural Margret Marquart Catholic Hospital, Kpando, Ghana during the time period from October 2019−December 2021. Urine samples from 348 patients (median age 40 years, 52.6% male) were examined. Of these, 125 (35.9%) showed either fungal or bacterial growth, including Escherichia coli in 48 (38.4%), Candida species (spp.) in 29 (23.2%), Klebsiella spp. in 27 (21.6%), Proteus spp. in 12 (9.6%), Citrobacter spp. in 10 (8.0%), Salmonella spp. in 4 (3.2%), Staphylococcus spp. in 3 (2.4%), and Pseudomonas spp. in 2 (1.6%) cases. Two bacterial spp. were detected in 7 samples (5.6%). Antibiotic susceptibility testing showed resistance to a mean 8.6 out of 11 tested antibiotics per patient. Significant predictors (p < 0.05) of bacterial growth were age (OR 1.03), female sex (OR 3.84), and the number of pus cells (OR 1.05) and epithelial cells (OR 1.07) in urine microscopy. We observed an alarmingly high AMR rate among the uropathogens detected, even to reserve antibiotics. A similar resistance profile can be expected in West African patients living in high-income countries. These observations warrant the implementation of restrictive antibiotic protocols, together with the expansion of urine culture testing capacities, improvement of documentation and reporting of AMR rates, and continued research and development of new antibiotic therapies in order to stem the progression of AMR in this West African region.

Long-Term Follow-Up after Testicular Torsion: Prospective Evaluation of Endocrine and Exocrine Testicular Function, Fertility, Oxidative Stress and Erectile Function.

Background: This study investigates endocrine and exocrine testicular function, oxidative stress (OS) in semen, and erectile function in patients who underwent surgery for suspected testicular torsion (TT). Methods: We evaluated 49 patients over a mean follow-up of 101 months: n = 25 patients treated with surgical exploration, n = 20 patients treated with detorsion, and n = 4 treated with orchiectomy. We performed semen analysis including Male infertility Oxidative System (MyOxSIS) analysis, physical examination, and evaluation of endocrine and erectile function. Results: OS, erectile function and spermiogram categories did not differ significantly between the groups. The interval from the onset of symptoms to surgery differed significantly between groups (p < 0.001). Preservation of the testes was associated with a higher round cell count (p = 0.002) and follicle stimulating hormone (FSH, p = 0.003). OS showed a significant positive correlation with the spermiogram category (0.337; p = 0.022). A negative correlation was observed between OS and age (p = 0.033), sperm concentration (p < 0.001) and total sperm count (p = 0.006). Conclusions: Endocrine, exocrine and erectile function are not significantly affected by TT in the long term. Orchiectomy results in elevated FSH and a lower round cell count compared to preservation of the testis.

Neoadjuvant Chemotherapy before Nephroureterectomy in High-Risk Upper Tract Urothelial Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant chemotherapy is a well-established concept in muscle-invasive bladder cancer with known advantages in overall survival. Phase II trials show encouraging response rates for neoadjuvant immunotherapy before radical surgery in urothelial cancer. There is no recommendation for neoadjuvant therapy in upper tract urothelial carcinoma before nephroureterectomy. Our aim was to assess the available data on neoadjuvant chemotherapy and immunotherapy before nephroureterectomy in patients with high-risk upper tract urothelial carcinoma in terms of pathological downstaging and oncological outcomes. Two investigators screened PubMed/Medline for comparative trials in the English language. We identified 368 studies and included eleven investigations in a systematic review and meta-analysis for neoadjuvant chemotherapy and control groups. There were no comparative trials investigating immunotherapy in this setting. All 11 studies reported on overall pathological downstaging with a significant effect in favor of neoadjuvant chemotherapy (OR 5.17; 95%CI 3.82; 7.00). Pathological complete response and non-muscle invasive disease were significantly higher in patients receiving neoadjuvant chemotherapy (OR 12.07; 95%CI 4.16; 35.03 and OR 1.62; 95%CI 1.05; 2.49). Overall survival and progression-free survival data analysis showed a slight benefit for neoadjuvant chemotherapy. Our results show that neoadjuvant chemotherapy is effective in downstaging in upper urinary tract urothelial carcinoma. The selection of patients and chemotherapy regimens are unclear.

The Diagnostic Value of the Added MR Imaging of the Scrotum in the Preoperative Workup of Sonographically Indeterminate Testicular Lesions-A Retrospective Multicenter Analysis.

BACKGROUND: The purpose of this study was to retrospectively analyze the diagnostic accuracy of magnetic resonance imaging (MRI) examinations of the scrotum in comparison with standard ultrasound (US) and histopathology. METHODS: A retrospective multi-center analysis of MRI examinations of the scrotum performed between 06/2008 and 04/2021 was conducted. RESULTS: A total of n = 113 patients were included. A total of 53 histopathologies were available, with 52.8% malignant and 50.9% benign findings. Related to histopathology, imaging was true negative, false negative, false positive, and true positive in 4.1%, 2.1%, 25.0% and 37.5% for standard ultrasound (US) and 9.1%, 1.8%, 25.5% and 43.6% for MRI. Sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 20.0%, 36.0% and 88.9% for US and 85.7%, 72.8%, 52.1% and 93.7% for MRI, respectively. Benign lesions were significantly smaller than malignant ones in standard US (p = 0.001), histopathology (p = 0.001) and MRI (p = 0.004). The size of malignant tumors did not differ significantly between histopathology and standard US (0.72) and between histopathology and MRI (p = 0.88). CONCLUSIONS: MRI shows good sensitivity and specificity for the estimation of testicular tumors in this collective. Benign lesions are significantly smaller than malignant ones. Both MRI and US can estimate the size of malignant tumors adequately.

Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study.

Introduction: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population. Patients and Methods: In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively. Results: The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate. Conclusion: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.

From Interferon to Checkpoint Inhibition Therapy-A Systematic Review of New Immune-Modulating Agents in Bacillus Calmette-Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC).

BACKGROUND: In Bacillus Calmette-Guérin (BCG) refractory non-muscle-invasive bladder cancer (NMIBC), radical cystectomy is the gold standard. The advent of immune checkpoint inhibitors (CPIs) has permanently changed the therapy landscape of bladder cancer (BC). This article presents a systematic review of immune-modulating (IM) therapies (CPIs and others) in BCG-refractory NMIBC. METHODS: In total, 406 articles were identified through data bank research in PubMed/Medline, with data cutoff in October 2021. Four full-text articles and four additional congress abstracts were included in the review. RESULTS: Durvalumab plus Oportuzumab monatox, Pembrolizumab, and Nadofaragene firadenovec (NF) show complete response (CR) rates of 41.6%, 40.6%, and 59.6% after 3 months, with a long-lasting effect, especially for NF (12-month CR rate of 30.5%). Instillations with oncolytic viruses such as NF and CG0070 show good efficacy without triggering significant immune-mediated systemic adverse events. Recombinant BCG VPM1002BC could prove to be valid as an alternative to BCG in the future. The recombinant pox-viral vector vaccine PANVAC™ is not convincing in combination with BCG. Interleukin mediating therapies, such as ALT-803, are currently being studied. CONCLUSION: CPIs and other IM agents now offer an increasing opportunity for bladder-preserving strategies. Studies on different substances are ongoing and will yield new findings.

On the black slope: analysis of the course of a blunt renal trauma collective in a winter sports region.

PURPOSE: The aim of this study was to analyze the injury patterns and clinical course of a winter sport dominated by blunt renal trauma collective. METHODS: Blunt renal trauma cases (N = 106) treated in a Level 1 Trauma Center in Austria were analyzed. RESULTS: We encountered 12.3% grade 1, 10.4% grade 2, 32.1% grade 3, 38.7% grade 4 and 6.6% grade 5 renal traumata classified according to the American Association for the Surgery of Trauma (AAST). The mechanisms of injury (MOI) did not have an influence on the frequency of HG trauma (i.e., grade 4 and 5). No concomitant injuries (CIs) were found in 57.9% of patients. The number of patients without CIs was significantly higher in the sports associated trauma group compared to other MOIs (p < 0.01). In 94.3% the primary treatment was a non-operative management (NOM) including 56.6% conservative, 34.0% endourological, and 3.8% interventional therapies. A follow-up computed tomography (FU-CT) was performed in 81.1%, 3.3 days after trauma. After FU-CT, the primary therapy was changed in 11.4% of cases (grade ≥ 3). Comparing the Hb loss between the patients with grade 3 and 4 kidney trauma with and without revision surgery, we find a significantly increased Hb loss within the first 96 h after the trauma in the group with a needed change of therapy (p < 0.0001). The overall rate of nephrectomy (primary or secondary) was 9.4%. Independent predictors of nephrectomy were HG trauma (p < 0.01), age (p < 0.05), and sex (p < 0.05). The probability of nephrectomy was lower with (winter) sports-associated trauma (p < 0.1). CONCLUSIONS: Sports-associated blunt renal trauma is more likely to occur isolated, and has a lower risk of severe outcomes, compared to other trauma mechanisms. NOM can successfully be performed in over 90% of all trauma grades.

Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy-A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin.

BACKGROUND: In the first and second-line therapy of metastatic urothelial carcinoma (mUC), checkpoint inhibitors (CPI) such as Pembrolizumab and Atezolizumab have been widely implemented. Little is currently known about what therapeutic options are effective after therapy with CPI. This article presents a systemic review of current treatment options in this setting. METHODS: From August 2020 to 15 April 2021, a literature search was performed through the PubMed/Medline. Subsequently, a single-group meta-analysis of three studies testing Enfortumab vedotin (EV) was conducted. RESULTS: Five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), EV, and Sacituzumab govitecan (SG). In n = 74 + 125 + 288 patients, the single-group meta-analysis showed an objective response rate of 42.1% for EV compared to 17.9% for CT in a similar setting. EV was also ahead in progression free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). CONCLUSION: Most data are currently available for EV. Further research is needed on the question of which patients' subcollectives particularly benefit from which therapeutic approach.

Electrosurgery or laser for benign prostatic enlargement: trumpcard or pitfalls.

PURPOSE OF REVIEW: To summarize and comment on publications of the last 2 years in the field of endoscopic surgery for benign prostatic enlargement, focusing on similarities and differences of laser and electrosurgery. RECENT FINDINGS: Because of good hemostasis and safety, invasive endoscopic surgery has evolved to a choice of treatment for vulnerable patients with ongoing antithrombotic medication and in same-day surgery. Recent publications show a good perioperative course and no deterioration in the postoperative outcome. Furthermore, alterations to the original surgical techniques of resection, enucleation, and vaporization have increased the preservation rate for antegrade ejaculation, advancing them to an appealing choice of treatment for sexually active men. Favorable outcomes can be achieved in both laser and electrosurgery. Only the choice of the surgical technique determines the outcome. SUMMARY: Various invasive endoscopic surgical techniques are available, offering different advantages and disadvantages for the patient. All of them can be performed with laser and electrosurgery. Therefore, focusing on the proper choice of surgical technique instead of the energy source will guarantee the patient to benefit most.

Adherence to the EAU Guideline Recommendations for Local Tumor Treatment in Penile Cancer: Results of the European PROspective Penile Cancer Study Group Survey (E-PROPS).

INTRODUCTION: Penile cancer (PeCa) is an orphan disease in European countries. The current guidelines are predominantly based on retrospective studies with a low level of evidence. In our study, we aimed to identify predictors for guideline-conform treatment and hypothesize that reference centers for PeCa and physicians' experience promote guideline compliance and therefore correct local tumor therapy. METHODS: This study is part of the European PROspective Penile Cancer Study (E-PROPS), an international collaboration group evaluating therapeutic management for PeCa in Central Europe. For this module, a 14-item-survey was developed and sent to 681 urologists in 45 European centers. Three questions focused on therapeutic decisions for PeCa in clinical stage Tis, Ta-T1a, and T1b. Four questions addressed potential personal confounders. Survey results were analyzed by bootstrap-adjusted stepwise multivariate linear regression analysis to identify predictors for EAU guideline-conform local treatment of PeCa. RESULTS: For local therapy of cTis 80.4% recommended guideline-conform treatment, for cTa-cT1a 87.3% and for cT1b 59.1%. In total, 42.4% chose a correct approach in all tumor stages. The number of PeCa patients treated at the hospital, a higher level of training of the physicians, resource-based answering and the option of penile-sparing surgery offered at the hospital matched with giving guideline-conform recommendations and thus accurate local tumor treatment. CONCLUSION: Patients with PeCa are best treated by experienced physicians, in centers with a high number of cases, which also offer a wide range of local tumor therapy. This could be offered in reference centers.

Laparoscopic Radical Cystectomy and Ileal Neobladder for Muscle Invasive Bladder Cancer in Combination with One Stage Prophylactic Laparoscopic Sacrospinal Fixation to Avoid Future Pelvic Organ Prolapse.

BACKGROUND: Women who undergo cystectomy with orthotopic ileal neobladder are more likely to have urinary retention and neocystocele mainly because of anatomical reasons than stress urinary incontinence. The risk is even higher in case of neurologic comorbidities, as in case of our patient. CASE PRESENTATION: We present a laparoscopic mesh insertion for sacrospinal colposuspension to prevent a neocystocele and pelvic organ prolapse in combination with laparoscopic radical cystectomy in a female patient suffering from bladder cancer and chronic episodic multiple sclerosis. After a 30-month follow-up, the patient is continent and voids without residual urine. A dynamic MR of the pelvis shows a minimal rectocele without any evidence of a cystocele. CONCLUSION: Laparoscopic cystectomy combined with sacrospinal mesh fixation is technically feasible and could be an option to prevent neocystocele for female patients.

Increased expression of claudin-1 and claudin-7 in liver cirrhosis and hepatocellular carcinoma.

Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and -7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and -7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation.

Tricellulin expression and its prognostic significance in primary liver carcinomas.

Numerous data suggest that altered expression of tight junction proteins such as occludin and claudins plays important role in carcinogenesis. However, little is known about tricellulin, a transmembrane tight junction protein concentrated where three epithelial cells meet. We aimed to characterize tricellulin expression in normal and cirrhotic liver in comparison to primary hepatic neoplasms. Tricellulin expression of 20 control livers, 12 cirrhotic livers, 32 hepatocellular carcinomas (HCC), and 20 intrahepatic cholangiocarcinomas (iCCC) was investigated by immunohistochemistry and Western blotting. Co-localization of tricellulin with claudin-1, -4, and MRP2 was studied using double immunofluorescence. Scattered tricellulin immunopositivity was restricted to biliary pole of hepatocytes confirmed by co-localization with MRP2. Moreover, spotted-like reaction was observed between bile duct epithelial cells. In 40 % of HCCs marked tricellulin overexpression was measured regardless of tumor grades. In iCCCs, however, tricellulin expression decreased parallel with dedifferentiation. In HCCs high tricellulin expression, in iCCCs low tricellulin expression correlated with poor prognosis. Co-localization with MRP2 might substantiate that tricellulin plays role in blood-biliary barrier. Overexpressed tricellulin in a subset of HCCs correlated with unfavorable prognosis. Similar to ductal pancreatic adenocarcinoma, higher grades of iCCCs were associated with decreased tricellulin expression correlating with poor prognosis.

Molecular characteristics of fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) occurs in non-cirrhotic liver and the etiopathogenesis is still obscure. Both hepatocellular and cholangiocellular markers are expressed in the tumor, however, molecular alterations and altered pathways playing role in the tumor pathogenesis are not clearly identified. The purpose of the present study was to compare the expression level of EGFR, syndecan-1 and ß-catenin in FLC, conventional hepatocellular carcinoma (cHCC) and cholangiocellular carcinoma (CCC) and to investigate the possibility of mutation both in EGFR and K-RAS. Eight FLCs were compared with 7 cHCCs, 7 CCCs and 5 normal liver samples. Cytokeratins 7, 8, 18, 19, HepPar1 (HSA), EGFR, syndecan-1 (CD138) and ß-catenin were detected by immunohistochemistry. In addition EGFR, ß-catenin and syndecan-1 were evaluated by digital morphometry and K-RAS, EGFR mutations in FLC cases using paraffin-embedded samples. All FLCs were positive for HepPar1 (HSA) and cytokeratins 7, 8, 18, but negative for cytokeratin 19 by immunohistochemistry. EGFR was significantly overexpressed in all three tumor types, being highest in FLCs (p = 0,0001). EGFR, K-RAS mutation analyses revealed no mutations in exons studied in FLCs. Our findings proved that expression of EGFR is higher in FLC than in other types of primary malignant hepatic tumors and no K-RAS mutation can be detected, so FLC is a good candidate for anti-EGFR treatment.