Publications

A prospective study on 16 patients with advanced (stage III and IV) prostate cancer was carried out. TNM stage, general clinical status, serum PSA level, the histological type and Gleason's grade of the tumor were registered. Total androgen blockade or single-drug therapy (flutamide) was performed. On average, 4.81 months after the start of therapy rebiopsy, serum PSA determination and general clinical examination were performed. Histologic examination before and after treatment of HE-stained slides, as well as apop-tag reaction to show apoptotic cells, p53, bcl(2), and Ki-67 immunostaining. Clinical improvement manifested by regression or lack of progression was observed in 10 patients. Increase of the apoptotic index and decrease of the mitotic index was detected in these cases. Serum PSA level decreased in all patients except in 3 fatal cases. The 6 clinically nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index. Ki-67 positivity correlated well with the mitotic activity. Mutant p53 expression was higher in patients in whom antiandrogen therapy was ineffective. The bcl(2) expression was a characteristic of the tumors of patients who later died. These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case. A given prostate cancer patient's response to therapy may be predicted by following apoptotic and mitotic activity, as well as Ki-67 and p53 expression in repeated biopsies.

Altogether, 40 patients with advanced prostate cancer received the LH-RH analog, Decapeptyl (D), as monotherapy for 1 month. The dose of D was 3.75 mg/month, intramuscularly in microcapsules. Needle biopsy was taken from the prostate of 20 patients at 24 hours, of 10 patients at 7 days, and of 10 patients at 30 days after the injection. The biopsy samples were investigated for mitotic and apoptotic indices as well as expression of p53 and Ki67 in the tumor cells. The effect of the LH-RH analog was manifested in very low and even absent mitotic activity in all points in time. The expression of mutant p53 was high (above 80%) in all 1-day and 7-day samples and in 8 of 10 samples taken 30 days after the start of the therapy. In 2 cases, the ratio of p53-expressing tumor cells was 2% and 5%. At day 30, the previously high ratio of Ki67-positive tumor cells decreased to 2-10% in 8 cases and showed focally higher values (70-90%) in 2 cases. Extremely high (90-100%) apoptosis could be registered in scattered foci of the tumor tissue in all samples taken 1 and 7 days after D injection. The other parts of the tumor tissue showed lower (1-5%) apoptotic activity. At day 30 after the injection, the same phenomenon was observed in 4 cases, but in 6 cases the apoptotic ratio became diffusely low (1-2%). Focal increase of apoptosis observed in the 1- and 7-day samples may be attributed to the direct effect of the LH-RH analog on tumor cells. The findings at day 30 indicate a considerable decrease in proliferating activity and, in the majority of cases, also in apoptotic activity, reflecting the effect of D on the pituitary-gonadal axis.

We developed a special calculation method for the compensation of resistance in urodynamic studies of the upper urinary tract that allows us to use existing single lumen nephrostomy catheters. We integrated a new calibration routine into the setup of our urodynamic equipment. Following the initial calibration procedure using the same size catheter as the previously inserted nephrostomy catheter, our software calculates actual resistance based on actual flowrate and the known linear resistance-flow correlation. Actual resistance and calculated intrapelvic pressure curves are presented in real-time. Using single lumen nephrostomy catheters for pressure-flow studies allows us to consider intrapelvic pressure during the measurement, to adjust filling pressure accordingly. It makes time consuming and sophisticated postprocessing resistance calculation unnecessary and also provides a challenging new method for conventional urodynamic studies of the lower urinary tract.

Objectives: To define an exact pressure-flow correlation in the upper urinary tract using an improved measurement method, to quantitatively characterize the degree of postrenal obstruction and to find a simple way of calculating it in everyday urological practice.

Methods: The data of 112 cases were included in the analysis. The dynamic method of a multistep, constant pressure perfusion study was used to precisely measure a wide range of pressure-flow dependences. Values of established parameters measuring the degree of obstruction were compared: the intrapelvic pressure, the ureteral opening pressure and the newly introduced 'obstruction coefficient'.

Results: Pressure-flow relations can be best presented by a parabolic curve described by the simple formula Y = AX(2) + B. Depending on the degree of obstruction, the shape of this curve can be characterized by a single number, that we defined as the 'obstruction coefficient'. Computer-based evaluation software for the easy calculation of this coefficient is presented here and freely available on demand. The Whitaker-test, the ureteral opening pressure, and the 'obstruction coefficient' showed significant correlation proving that the latter was clinically applicable in measuring the degree of obstruction.

Conclusion: Calculation of the 'obstruction coefficient' enables us to exactly define the degree of upper urinary tract obstruction and to safely monitor for a long period conditions inhibiting ureteric passage.

A 62-year-old female patient, symptomfree hematuria was found. Ultrasonography and computed tomography (CT) scan showed an endophytic mass on the medial pelvic wall on the solitary, right kidney. Nephrectomy was offered to the patient. Due to the solitary kidney, this would have meant lifelong hemodialysis for her. She refused nephroureterectomy but was ready to consider kidney-sparing operative solution. Therefore, percutaneous resection of the tumor, rather than nephroureterectomy was discussed. In order to decide such an operation, we had to prove with full certainty that there were no other small lesions in the pelvis. Noninvasive virtual pyeloscopy, rather than semirigid or flexible ureterorenoscopy, served this purpose.

Aims: To present a rationale for the inclusion of urothelial coating dysfunction in the etipathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) and the preclinical and clinical evidence in support of glycosaminoglycan (GAG) replenishment therapy in the treatment of BPS/IC, supplemented by the clinical experience of medical experts in the field and patient advocates attending a symposium on GAG replenishment at ESSIC'17, the annual Meeting of the International Society for the Study of Bladder Pain Syndrome, held in Budapest, Hungary in 2017.

Results: The urothelial GAG layer has a primary role in providing a permeability barrier to prevent penetration of urinary toxins and pathogens into the bladder wall. Disruption of the GAG layer contributes to the development of BPS/IC. The evidence shows that replenishment of GAGs can restore the GAG layer in BPS/IC, reducing inflammation, pain, and other symptoms.

Conclusions: Although data from large randomized controlled studies are limited, long clinical observation and the experience of clinicians and patients support the beneficial effects of intravesical GAG replenishment therapy for providing symptomatic relief for patients with BPS/IC.

Key words: bladder pain syndrome; chondroitin sulfate; clinical practice; diagnosis; gag layer replenishment; glycosaminoglycans; hyaluronic acid; interstitial cystitis.

Objective: The intravesical instillation of bladder cocktails via catheter is a widely spread, most effective way of treatment of interstitial cystitis/bladder pain syndrome. This disease often affects the urethra too, causing tenderness and pain. Therefore, catheterization causing superficial mucosal lesions triggers strong and long-lasting pain, sometimes bleeding, and a higher risk of infection.

Methods: We invented an adapter fitting on both Luer-lock and Luer-slip syringes allowing the injection of "bladder cocktails" into the bladder through the urethra in a retrograde way; the injected fluid opens the bladder sphincter. Its radiused tip and the specially shaped flexible isolating collar allow us to perform drop-free instillation without catheterization. In the last 2 years, clinical evaluations were conducted in 270 interstitial cystitis/bladder pain syndrome patients (243 female, 27 male), altogether totalling 1520 instillations.

Results: In 5 of 243 female patients (2%) using the syringe adapter was unsuccessful due to the deep located urethral orifice or cicatricose vaginal opening. This made visualization of the urethral orifice impossible (success rate: 98%). All the 27 male patients (100%) could be treated without any difficulties. No infection due to the instillation was observed. All treatable patients preferred the catheter-free method to conventional catheterization. They did not report any pain, long-lasting burning sensation or any other complications.

Conclusions: The new non-invasive instillation method prevents superficial lesions of the urethra and treats urethral and bladder mucosa simultaneously. It reduces pain and the complication rate compared to conventional catheterization and at the same time reduces time, costs and inconvenience of bladder instillation.

Key words: bladder pain syndrome; catheter-free bladder instillation; interstitial cystitis; intravesical instillation therapy; syringe adapter.

Purpose of the meeting: Bladder pain syndrome/interstitial cystitis is a prevalent but underserved disease. At the Global Interstitial Cystitis/Bladder Pain Syndrome Society (GIBS) meeting, the organization and participants were committed to delivering word-class expertise and collaboration in research and patient care. Under the umbrella of GIBS, leading research scholars from different backgrounds and specialties, as well as clinicians, from across the globe interested in the science and art of practice of Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) were invited to deliberate on various dimensions of this disease. The meeting aimed to have global guidelines to establish firm directions to practicing clinicians and patients alike on the diagnosis and treatment of this disease entity. Chronic Pelvic Pain Syndrome (CPPS) is defined by pain in the pelvic area that can have different etiologies. This can be due to urologic, gynecologic, musculoskeletal, gastrointestinal, neurologic, and autoimmune or rheumatologic diseases. At the GIBS meeting held in Mumbai, India, in August 2019, a multidisciplinary expert panel of international urologists, gynecologists, pain specialists, and dietitians took part in a think tank to discuss the development of evidence-based diagnostic and treatment algorithms for BPS/IC.

Summary of presented findings: The diagnosis of BPS/IC is difficult in daily clinical practice. Patients with BPS/IC present with a variety of signs and symptoms and clinical test results. Hence, they might be misdiagnosed or underdiagnosed, and the correct diagnosis might take a long time. A good history and physical examination, along with cystoscopy, is a must for the diagnosis of IC/BPS. For the treatment, besides lifestyle management and dietary advice, oral medication and bladder instillation therapy, botulinum toxin, and sacral neuromodulation were discussed. The innovation in bladder instillation applicators, as well as battery-free neuromodulation through the tibial nerve, was discussed, as well.

Recommendation for future research: As BPS/IC is complex, for many patients, several treatments are necessary at the same time. This was presented at GIBS 2019 as the piano model. In this way, a combination of treatments is tailored to an individual patient depending on the symptoms, age, and patients' characteristics. In the art of medicine, especially when dealing with BPS/IC patients, pressing the right key at the right time makes the difference.

Key words: Bladder Pain Society; Bladder Pain Syndrome; Global Interstitial Cystitis; Interstitial Cystitis Beyond Horizon.