Bladder Pain Syndrome and Interstitial Cystitis Beyond Horizon: Reports from the Global Interstitial Cystitis/Bladder Pain Society (GIBS) Meeting 2019 Mumbai - India.

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.

Minimally invasive device for intravesical instillation by urological syringe adapter (MID-ii U.S.A.) for catheter-free instillation therapy of the bladder in interstitial cystitis/bladder pain syndrome.

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.

GAG replenishment therapy for bladder pain syndrome/interstitial cystitis.

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.

A novel quantitative method for measuring obstruction in the upper urinary tract: the 'obstruction coefficient'.

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.

Real-time flow resistance compensation for urodynamic examinations of the upper urinary tract through single lumen catheters.

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.

[The role of repeated biopsies in prognosis of prostate cancer]. / Prostatadaganat prognózisának vizsgálata ismételt biopszia segítségével.

INTRODUCTION: The treatment of prostate cancer is still controversial. One of the most common treatment form is the use of LHRH analogs, but its way of action is still not cleared enough. AIMS: The aim of this study was to determine the predictive value of some histological and immuno-histochemical parameters based on repeated biopsies taken from prostate carcinoma patients. PATIENTS/METHOD: At the time of diagnosis by needle biopsy the TNM stage, serum PSA level, Gleason's grade, apoptotic and mitotic index, as well as Ki67, p53 and bcl2 expression were investigated in 60 prostate carcinoma patients. Anti-androgen therapy supplemented with surgical or chemical castration (with LHRH analogs) was administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53 and bcl2 expression. RESULTS: Forty-seven patients were alive at the end of the study (average 23.46 +/- 8.6 months) and thirteen patients died (average 25.3 +/- 14.8 months). Initial TNM stage and Gleason's score proved to be of prognostic value. Decrease in mitotic index and increase in apoptotic index during therapy proved to predict favourable long-term response to androgen ablation therapy. Similarly, lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to a favourable effect of antiandrogen and especially of LHRH analog treatment. Since the ratio between Ki67 percentage and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio may be recommended as a histologically detectable predictive factor. However, bcl2 expression did not show significant correlation with the outcome of the disease. CONCLUSION: Histological evaluation of parameters such as mitotic and apoptotic index as well as Ki67 and p53 expression in repeated biopsies during treatment may contribute to predicting the value of the actual treatment and may be useful to institute alterations in therapy.