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Purpose Acute radiation cystitis, inflammation of the bladder, is a common side effect in men receiving external beam radiation for prostate cancer. Although several treatments provide symptomatic relief, there is no effective treatment to prevent or treat radiation cystitis. Cranberry products have been associated with urinary tract health. This study aimed to determine the effect of highly standardized cranberry capsules (containing 72 mg proanthocyanidins [PACS]) compared with that of placebo capsules on the incidence and severity of radiation cystitis. Methods Forty-one men with prostate cancer participated in a double blinded randomized placebo controlled study. Men took one capsule a day at breakfast during treatment and for 2 weeks after treatment completion. Severity of urinary symptoms and the bother these caused were measured using the individual items of the urinary domain of the Modified Expanded Prostate Index Composite (EPIC). Results The incidence of cystitis was lower in men taking cranberry capsules (65 %) compared with those that took placebo capsules (90 %) ( p  = 0.058); severe cystitis was seen in 30 % of men in the cranberry arm and 45 % in the placebo arm ( p  = 0.30). Overall, the incidence of pain/burning was significantly lower in the cranberry cohort ( p  = 0.045). Men on the low hydration regimen who took cranberry had less pain/burning ( p  = 0.038), stronger urine steam ( p  = 0.030) and used significantly fewer pads/liners ( p  = 0.042), which was significantly different from those on the high hydration regimen ( p  = 0.028). Conclusion Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or with baseline urinary symptoms.

In women with diabetes, treatment of asymptomatic bacteriuria has been recommended to prevent complications. In this trial, 55 women with diabetes and asymptomatic bacteriuria were randomly assigned to receive antimicrobial therapy and 50 to receive placebo. After a mean follow-up of 27 months, the rates of symptomatic urinary tract infection were similar: 42 percent in the treated group and 40 percent in the placebo group. There were also no significant differences between the two groups in the rates of pyelonephritis or hospitalization for urinary tract infection, although the 95 percent confidence intervals for these differences were wide. Urinary tract infection is a common clinical problem in women with diabetes mellitus. Such women probably have a higher frequency of symptomatic infection than do women without diabetes, 1 and they also have more severe infections, with an increased risk of hospitalization for pyelonephritis 2 and a higher frequency of bacteremia 3 and bilateral renal involvement. 4 Serious, but uncommon, complications of urinary tract infection, including emphysematous cystitis 5 and pyelonephritis, 6 and intrarenal 7 and perinephric 8 abscess, occur primarily in patients with diabetes. Asymptomatic bacteriuria is three times as common among women with diabetes as among women without this condition. 9 In the United States, some groups . . .

Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. We did a randomised, controlled, phase 2–3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen—A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18–80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30–40 sessions, 100% oxygen, breathed at a pressure of 240–250 kPa, for 80–90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6–8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210–262) in the hyperbaric oxygen therapy group and 217 days (195–237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2–18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1–2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients’ population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting.

Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well known. We evaluated HC in a large cohort ( n =1321, 2003–2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute GVHD, fever, severe thrombocytopenia and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III–IV) was associated with increased treatment-related mortality but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis, and early interventions to limit its severity are still needed.

Introduction: Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by inflammation and bleeding of the bladder. Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of radiation-induced HC. However, the optimal treatment for HC after allogeneic HSCT has not yet been established. Furthermore, limited research has been conducted on the use of HBOT in this setting. This study aimed to evaluate the effectiveness and safety of HBOT in patients with late-onset HC after allogeneic HSCT. Methods: Twenty-five-year (1998–2022) retrospective analysis performed in all consecutive patients with confirmed late-onset HC after allogeneic HSCT treated with HBOT at two centers in Portugal. Medical records were reviewed for clinical and laboratory features, primary indications for allogeneic HSCT, conditioning regimen, and treatment strategies for HC. Patients received 100% oxygen at 2.1–2.5 atmosphere absolute pressure (ATA) for 70–90-minute periods, once daily, five times per week. Complete clinical response was defined as the absence of macroscopic hematuria sustained for at least 2 weeks, and partial response was described as a downgrading in the severity of HC. Statistical significance was considered for values of p < 0.05. Results: The sample included 61 patients with a mean age of 28.0 (SD 14.2) years, 33 males. Complete response was achieved in 72.1% (n = 44) of patients and partial response in 14.8% (n = 9). Concerning patients with a complete response, the median number of HBOT sessions was 15.5 sessions (IQR 10.0-26.8). Patients treated with 10 or more sessions of HBOT had a higher rate of complete or partial response (OR 12.5, 95%CI 1.9–83.2, p-value < 0.05). There was no response in 8 (13.1%) patients, and 6 interrupted the treatments early. Only 2 patients suspended the HBOT due to a lack of clinical benefit. Conclusion: Our study supports using of HBOT as an adjunctive treatment for late-onset HC after allogeneic HSCT. Furthermore, 10 or more HBOT sessions delivered seem to impact the rate of HC resolution. Prospective, randomized, and well-controlled trials are needed to establish HBOT’s definitive efficacy and safety.

The underlying mechanism of radiation cystitis remains unknown, however, angiogenesis induced by hypoxia seems to be important because hyperbaric oxygen therapy which suppresses HIF-1 is clinically effective and significantly associated with androgen receptor signaling. We herein assessed the impact of androgen deprivation therapy on radiotherapy-induced bladder hemorrhage in men with prostate cancer and that of androgen receptor signaling on angiogenesis in irradiated bladder cell lines and a mouse model of radiation cystitis. In 507 patients with prostate cancer undergoing external beam radiation therapy, univariate (hazard ratio 0.61, p  = 0.039) and multivariate (hazard ratio 0.50, p  = 0.006) analyses revealed that the use of androgen deprivation therapy was associated with a significantly lower risk of gross hematuria. In irradiated bladder cells, the levels of FLT1 and KDR expression were significantly elevated when pretreated with dihydrotestosterone, which was abolished by an anti-androgen hydroxyflutamide. In male mice with radiation cystitis, castration significantly reduced the incidence of hematuria. Correspondingly, microvessel density and VEGFR expression in the bladders in the castration group were significantly lower than those in the sham surgery group. Our results suggest that androgen receptor activation contributes to inducing angiogenesis in irradiated bladder cells. Androgen deprivation therapy thus has a potential for preventing radiation cystitis.

Radiation cystitis (RC) is a clinically challenging and often progressive complication of pelvic radiotherapy, marked by urothelial injury, vascular dysfunction, chronic inflammation, and fibrotic remodeling. Early diagnosis remains elusive due to nonspecific symptoms and the absence of validated molecular tools. As a biofluid in direct contact with the irradiated bladder, urine offers a unique molecular window into RC pathogenesis. In this review, we synthesize the current landscape of urinary biomarkers associated with the acute, latent, and chronic phases of RC, including inflammatory cytokines, oxidative stress products, epithelial injury markers, extracellular vesicles, microRNAs, proteomic signatures, and metabolomic alterations. We also integrate emerging mechanistic insights such as DNA damage responses, ROS generation, mitochondrial dysfunction, urothelial barrier disruption, senescence-associated secretory phenotypes, hypoxia-driven vascular injury, and profibrotic TGF-β signaling, all of which contribute to the release of urinary analytes. By linking phase-specific molecular pathways with corresponding urinary signatures, we highlight opportunities to leverage urine-based measurements for early detection, risk stratification, severity assessment, and therapeutic monitoring. A deeper understanding of the molecular mechanisms shaping urinary biomarker profiles will be essential for advancing precision diagnostics and improving long-term outcomes for patients with radiation cystitis.

The use of radiotherapy has increased in recent years, especially for pelvic neoplasms, and this can result in long-term complications such as recurrent haemorrhagic radiation cystitis (RHC). A 73-year-old male patient presented to a hospital emergency department multiple times with visible haematuria and clots leading to urinary clot retention; he was finally diagnosed with RHC. During the last presentation, the bladder was irrigated continuously with saline using a three-way catheter. During hospitalisation, a cystourethroscopy was performed for bladder evaluation and clot evacuation. Multiple bleeding ulcers were recognised on the bladder wall, biopsies were taken for histopathology, and the ulcers cauterised. Packed red blood cell transfusions were required, and sodium hyaluronate (CystiStat ® ) bladder instillations were tried. There was no clinical improvement following any of these interventions. In light of the patient’s deteriorating condition, cystoscopic application of PuraStat ® 3ml was administered, which led to remission of the urinary bleeding in the short term. We continue to monitor the effects in the medium and long term. Based on current data, PuraStat ® haemostatic agent therapy may be considered for RHC, when traditional treatments are ineffective or infeasible, potentially eliminating the need for more aggressive therapy such as cystectomy.