A review of urinary bladder microbiome in patients with bladder cancer and its implications in bladder pathogenesis.

PURPOSE: The recent discovery of the urinary microbiome has led to an emerging field of investigation about the potential role of microorganisms in the pathogenesis of urinary bladder cancer. Few preliminary data have been reported so far implicating urobiome as causative and prognostic factor of bladder tumorigenesis. In the present study, a review of the current evidence is presented about microbiome composition among patients with bladder cancer and healthy individuals as well as possible implications of microbiome on urothelial carcinoma of the bladder. METHODS: A literature review was conducted using PubMed/MEDLINE, Scopus, and the Cochrane library until December 2023. Search algorithm was constructed using the following terms and their associated Mesh terms and Boolean operators: "urinary microbiome" and "urinary microbiota". Studies written in English language, identifying, and comparing urinary microbiome among bladder cancer patients and healthy control group were included in the review. RESULTS: A total of 2,356 reports were identified. From this total 16 articles complied with the inclusion criteria were selected for analysis. These articles represent a total of about 486 bladder cancer patients. CONCLUSION: Recent studies revealed the colonization of the urinary tract and the bladder by micro-organisms using both enhanced culture- and molecular-based techniques for microbial characterization. However, several limitations exist in the literature decreasing the reliability of the current reports. As a result, urinary microbiome consist an ambitious era in bladder cancer research with an increasing number of evidence about its potential pathogenetic, prognostic and therapeutic role.

PSMA-based therapeutics for prostate cancer.

INTRODUCTION: The prostate cancer (PCa) consists the most frequently diagnosed malignancy of urogenital system in males. Traditionally, treatment of localized PCa was based on surgery or radiotherapy while hormonotherapy was used in more advanced stages. However, the implementation of radiolabels has revolutionized the landscape of prostate cancer. Specifically, prostate-specific membrane antigen (PSMA) has been investigated in different aspects of PCa therapeutic era. AREAS COVERED: A literature review is presented about the implications of PSMA radiolabels on prostate cancer treatment. PSMA tracers were initially used as an imaging technique. Afterwards, PSMA labeled with isotopes presenting cytotoxic abilities, such as lutetium-117 and actinium-225, while reports exist about the use of radioligand immunotherapy. Meanwhile, ongoing trials examine the development of novel radionuclides as well as the evolution of the PSMA-targeted ligands. EXPERT OPINION: Currently, PSMA radioligand treatment of prostate cancer is approved in the metastatic stage of the disease. Meanwhile, a variety of trials exist about its possible role in less advanced stages. However, plenty of parameters should be addressed before these implementations, such as PSMA dosage, dosimetry issues, and its safety profile. A future well-designed study with proper patient selection is mandatory to further explore PSMA radioligand theranostics perspectives.

Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option.

Is there a role for hyberbaric oxygen as primary treatment for grade IV radiation-induced haemorrhagic cystitis? a prospective pilot-feasibility study and review of literature

Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary treatment for Grade IV radiation-induced haemorrhagic cystitis. Materials and Methods Hyperbaric oxygen was prospectively applied as a primary treatment option in 11 patients with Grade IV radiation cystitis. Primary endpoint was the incidence of complete and partial response to treatment. Secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications for a mean follow-up of 17.82 months (range 3 to 34). Mean number of sessions needed was 32.8 (range 27 to 44). Complete and partial response rate was 81.8% and 18.2%, respectively. However, in three patients the first treatment session was not either sufficient or durable giving a 72.7% rate of durable effect. Interestingly, all 9 patients with complete response received therapy within 6 months of the haematuria onset compared to the two patients with partial response who received therapy at 8 and 10 months from the haematuria onset, respectively (p = 0.018). The need for blood transfusion (p = 0.491) and the total radiation dose (p = 0.259) were not correlated to success-rate. One patient needed cystectomy, while all patients were alive at the end of follow-up. Conclusions Early primary use of hyperbaric oxygen to treat radiation-induced grade IV cystitis is an effective and safe treatment option. .

Reducing the number of sutures for vesicourethral anastomosis in radical retropubic prostatectomy

OBJECTIVE: To prospectively evaluate the outcome of using a two-suture technique for the vesicourethral anastomosis (VUA) during radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: Two groups of 50 patients each underwent nerve-sparing RRP for localized prostate cancer by one surgeon. In one group, the vesicourethral anastomosis was performed using 2 Vicryl 2-0 stitches placed at the 3- and 9-o’clock positions and in the other group 6 Vicryl 2-0 stitches were placed at the 2-, 4-, 6-, 8-, 10- and 12-o’clock positions. The intraoperative and perioperative parameters analyzed were time to perform the VUA, time to remove the drain and hospitalization. The rate of incontinence, anastomotic stricture and erectile function were included in the outcome analysis. RESULTS: The anastomotic time differed statistically between the 2 groups (mean 3.3 minutes for the 2-suture group and 10.5 minutes for the 6-suture group, p < 0.0001) with similar periods of drain removal (mean 3.12 days for the 2-suture group and 3.45 days for the 6-suture group; p = 0.13) and hospitalization (mean 4.66 days for the 2-suture group and 5.3 days for the 6-suture group; p = 0.09). The functional outcome was excellent for the 2-suture group with no patient suffering from incontinence or anastomotic strictures 1 year postoperatively, while in the 6-suture group there were 2 patients (4 percent) suffering from incontinence (2 underwent sling procedure) and 1 patient suffered from anastomotic stricture. CONCLUSION: The low number of sutures in the 2-suture VUA technique reduces operating times, does not influence perioperative and intraoperative parameters and results in excellent functional outcome.