Misdiagnosis of eosinophilic cystitis: A case report and literature review.

RATIONALE: Eosinophilic cystitis (EC) is a rare and specific transmural inflammatory disease in clinic. At present, its etiology is unknown, its clinical manifestations are diverse, and its auxiliary examination lacks specificity, so it is easy to be missed or misdiagnosed in clinical practice. PATIENT CONCERNS: A 72-year-old male patient with symptoms of lower urinary tract obstruction accompanied by hematuria was diagnosed with benign prostatic hyperplasia with bleeding by B-ultrasound and urinary CT examination. After being treated with catheterization, anti-infection and hemostasis, he was selectively treated with transurethral resection of prostate, but he saw a pattern mass on the right back wall of the bladder during the operation. Considering bladder tumor, he removed the lesion and gave pirarubicin for bladder perfusion. However, the postoperative pathological result was EC. DIAGNOSIS: The diagnosis of EC can only rely on pathological examination, and the accurate and positive rate of biopsy can be improved by obtaining muscle tissue as much as possible at the same time of multi-point biopsy. INTERVENTION: Prednisone and cetirizine were given orally after transurethral resection of lesions, and tamsulosin and finasteride were given regularly to treat benign prostatic hyperplasia. OUTCOMES: No recurrence and abnormal urination were found during the follow-up for half a year, and the upper urinary tract function was normal. LESSONS: The clinical manifestations of EC are atypical, the laboratory examination and imaging examination are not specific, and it is difficult to make a definite diagnosis before operation. The diagnosis depends on pathological examination. Transurethral resection of the lesion can obviously improve the positive rate of biopsy while completely removing the lesion, and the combined drug treatment can achieve satisfactory results in a short period of time. Active follow-up after operation is very important to identify the recurrence of the disease and prevent the upper urinary tract function from being damaged.

Haemorrhagic cystitis: a review of management strategies and emerging treatments.

Haemorrhagic cystitis (HC) is characterised by persistent haematuria and lower urinary tract symptoms following radiotherapy or chemotherapy. Its pathogenesis is poorly understood but thought to be related to acrolein toxicity following chemotherapy or fibrosis/vascular remodelling after radiotherapy. There is no standard of care for patients with HC, although existing strategies including fulguration, hyperbaric oxygen therapy, botulinum toxin A, and other intravesical therapies have demonstrated short-term efficacy in cohort studies. Novel agents including liposomal tacrolimus are promising targets for further research. This review summarises the incidence and pathogenesis of HC as well as current evidence supporting its different management strategies.

Advances in the management of radiation-induced cystitis in patients with pelvic malignancies.

OBJECTIVE: Radiotherapy plays a vital role as a treatment for malignant pelvic tumors, in which the bladder represents a significant organ at risk involved during tumor radiotherapy. Exposing the bladder wall to high doses of ionizing radiation is unavoidable and will lead to radiation cystitis (RC) because of its central position in the pelvic cavity. Radiation cystitis will result in several complications (e.g. frequent micturition, urgent urination, and nocturia) that can significantly reduce the patient's quality of life and in very severe cases become life-threatening. METHODS: Existing studies on the pathophysiology, prevention, and management of radiation-induced cystitis from January 1990 to December 2021 were reviewed. PubMed was used as the main search engine. Besides the reviewed studies, citations to those studies were also included. RESULTS AND DISCUSSIONS: In this review, the symptoms of radiation cystitis and the mainstream grading scales employed in clinical situations are presented. Next, preclinical and clinical research on preventing and treating radiation cystitis are summarized, and an overview of currently available prevention and treatment strategies as guidelines for clinicians is provided. Treatment options involve symptomatic treatment, vascular interventional therapy, surgery, hyperbaric oxygen therapy (HBOT), bladder irrigation, and electrocoagulation. Prevention includes filling up the bladder to remove it from the radiation field and delivering radiation based on helical tomotherapy and CT-guided 3D intracavitary brachytherapy techniques.

[Hyperbaric oxygen therapy for the treatment of radiation-induced cystitis]. / Oxygénothérapie hyperbare dans le traitement de la cystite radio-induite.

Radiation-induced cystitis (RIHC) is a late complication of pelvic radiation therapy defined by irritative lower urinary tract symptoms with recurrent and sometimes refractory hematuria. Conservative or endoscopic treatments are the first lines, but cystectomy in required in refractory cases. Hyperbaric oxygen therapy (HOT) has recently emerged in the management charts for recurrent and refractory hematuria. Thanks to its neoangiogenic and stem-cell stimulation properties, HOT achieves a complete resolution of hematuria in almost two third of patients and appears to be a good therapeutic alternative for this fragile population. However, its geographical availability is currently limited in Switzerland and its implementation can sometimes require long hospital stays.

La cystite radio-induite (CR) est une complication tardive de la radiothérapie pelvienne se présentant notamment sous forme de troubles mictionnels irritatifs ou de macrohématurie récidivante. Le traitement est initialement conservateur ou endoscopique mais peut, dans des cas réfractaires, aboutir à une cystectomie à visée hémostatique ou fonctionnelle. L'oxygénothérapie hyperbare (OHB) a récemment fait son apparition dans les diagrammes de prise en charge de la CR réfractaire. Grâce à ses propriétés néoangiogéniques et à la stimulation des cellules souches, elle permet une résolution complète de l'hématurie chez près de deux tiers des patients et semble être une alternative thérapeutique pour cette population fragile. Actuellement, sa disponibilité géographique reste toutefois limitée en Suisse et sa réalisation implique parfois de longues hospitalisations.

Hyperbaric oxygen treatment for late radiation-induced tissue toxicity in treated gynaecological cancer patients: a systematic review.

PURPOSE: The aim of this study was to investigate the result of hyperbaric oxygen therapy (HBOT) in women with treated gynaecological malignancies who suffer from late radiation-induced tissue toxicity (LRITT). Moreover, which symptoms of LRITT benefit most from HBOT was evaluated as well. MATERIAL AND METHODS: An online literature search was conducted using PubMed; Embase and the Cochrane Library. Studies were included if the study examined gynaecological cancer patients who had been treated with radiotherapy, who suffered from LRITT and who subsequently received HBOT. In addition, the outcome measures were based on examining the effects of HBOT. RESULTS: Twenty-one articles were included. The study investigating proctitis reported an improvement and three out of four studies investigating cystitis reported decreased complaints in women treated for gynaecological malignancies. In addition, all studies reported improvement in patients with wound complications and fifty percent of the studies reported better Patient Reported Outcome Measurements (PROMS) in women with gynaecological malignancies. Finally, all studies, except one related to pelvic malignancies reported reduced prevalence of symptoms for cystitis and proctitis and all studies reported better PROMS. However, only eleven studies reported p-values, nine of which were significant. CONCLUSION: This study demonstrated that HBOT has a positive effect in women with gynaecological LRITT. Within the included patient group, gynaecological cancer patients with wound complications seem to benefit most from this treatment compared to other late side effects of LRITT.

Efficacy, tolerance and predictors of response to the treatment with hyperbaric oxygen therapy for patients with hemorrhagic radiation cystitis.

OBJECTIVES: The aim was to study the efficacy and tolerance in patients with haemorrhagic radiation-induced cystitis (HRC) treated with hyperbaric oxygen therapy (HOT) and analyze which factors were related to the response to the treatment. MATERIAL AND METHODS: We performed a retrospective cohort study of patients treated with HOT for HRC symptoms in a provincial referral centre from 2010 to 2020. We evaluated clinical response to treatment, number of hospitalizations due to HRC and subjective response using the PGI-I questionnaire. RESULTS: We treated 52 patients, with a median of 30 sessions, during 6 months and 40 months (6-68 months) of follow-up. 69.2%of patients responded completely and 21,2% partially. The 53.2% of patients improved before the first 10 sessions. Reduction of hospitalizations/per year due to haematuria from 2.8 to 1.1 (p=0,001). The 73,5% of patients stated that they were "very much better" or "much better" after treatment. During the follow-up, 15.4% of patients had recurrence of HRC. 9.6% of the patients required salvage cystectomy. The patients with a highest RTOG-EORTC scale had more risk to still with symptoms (OR 3.01 (IC95 1.48 - 6.16). All patients were able to complete the proposed treatment plan with good tolerance to HOT. CONCLUSIONS: These results show the clinical benefit of HOT in the treatment of HRC, with a reduction of the number of hospitalizations and a subjective improvement.

Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant.

INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.

Two cases of Bacillus Calmette-Guérin cystitis treated with hyperbaric oxygen.

Hyperbaric oxygen (HBO2) therapy is a UHMS-approved treatment for radiation cystitis and has been used for other causes of cystitis such as cyclophosphamide-induced hemorrhagic cystitis and interstitial cystitis, among others. Immunotherapy with Bacillus Calmette-Guérin (BCG) is the most effective treatment of non-muscle invasive bladder cancer. BCG acts as a non-specific stimulant of the reticuloendothelial system, causing a local inflammatory response. BCG attaches to bladder tumor cells as well as urothelial cells which then stimulates an immune response involving a multitude of cytokines and local migration of polymorphonuclear cells that leads to death of the cancer cells. The typical protocol of a single six-week course has been shown to provide long-term protection from tumor recurrence and to reduce disease progression. Irritative bladder side effects are common, but serious side effects are uncommon. Two cases of severe BCG-cystitis treated with HBO2 are presented. Two male patients with bladder cancer were treated with intravesicular BCG. Each developed complications of pain, spasms, urinary frequency and nocturia; one developed gross hematuria. Cystoscopy showed friable mucosa. They failed standard medical therapy and were referred for HBO2. They were treated in a multiplace chamber at 2.2-2.4 ATA. One patient received 60 and the other 40 treatments. Both experienced substantial reduction in their symptoms. BCG cystitis may be considered for HBO2 if other standard therapy has failed.

Current management of radiation cystitis after pelvic radiotherapy: a systematic review.

INTRODUCTION: We aimed to summarize current literature about radiation cystitis treatments, providing physician of a summary of current management options. EVIDENCE ACQUISITION: A systematic literature review searching on PubMed (Medline), Scopus, and Web of Science databases was performed in March 2021. PRISMA guidelines were followed. Population consisted of patients with a diagnosis of radiation cystitis after pelvic radiotherapy (P). We focused our attention on different treatments, such as conservative or surgical one (I). Single or multiple arms studies were deemed eligible with no mandatory comparison (C). Main outcomes of interest were symptoms control and adverse events rates (O). EVIDENCE SYNTHESIS: The search identified 1194 records. Of all, four studies focused on the use of hyperbaric oxygen therapy showing complete response rates ranging from 52% to 87% approximately. Oral administration of cranberry compounds was investigated in one study showing no superiority to placebo. Intravesical instillation of different compounds were investigated in five studies showing the highest complete response rates after alum (60%) and formalin administration (75%). Endoscopic conservative surgical treatments (fibrin glue or vaporization) also showed 75% complete response rates. In patients who did not respond to conservative treatments robotic cystectomy is feasible with overall complication rates of about 59.3% at 90 days. CONCLUSIONS: Radiotherapy induced cystitis is an under-reported condition after pelvic radiotherapy. Several treatments have been proposed, but in up to 10% of cases salvage cystectomy is necessary. A stepwise approach, with progressive treatment aggressiveness is recommended.

[Hyperbaric oxygen therapy efficacy in the treatment of hematuria due to radiation cystitis. Experience in a reference center.] / Eficacia de la oxigenoterapia hiperbárica en el tratamiento de la hematuria por cistitis rádica. Experiencia en un centro de referencia.

OBJECTIVE: To evaluate the efficacy of hyperbaric oxygen therapy (HBOT) in the treatment of hemorrhagic radiation cystitis (HRC). MATERIAL AND METHOD: Retrospective study of patients diagnosed with hematuria secondary to HRC after pelvic radiation from January 2005 to January 2017 who were treated with HBOT. Demographic and clinical variables were collected. A descriptive univariate and multivariate statistical analysis using Cox regression was carried out. The treatment was considered effective when there was a total or partial remission of the hematuria based on the Radiation Therapy Oncology Group (RTOG) scoring schema. Partial remission was defined as the presence of hematuria grade 2 or less. RESULTS: A total of 67 patients with a mean age of 68,6 years (39-87) were included. 65,7% men and 34,3% women. The RT was administered in 64,2% of the cases by urological cause, prostate cancer. The av-erage dose of RT was 75,24 Gy (45-180). The mean from the RT to the HBOT treatment was 55,97 months (4-300) and from the beginning of the hematuria until the treatment was 11,3 months (1-48). Response was observed in 51 (76,1%) patients, total in 50,7% and partial in 25,4% of cases. Patients with a degree of hematuria less than 3, those who were administered more than 30 sessions and those who did not require transfusion or hospital admission, responded significantly bet-ter to treatment with HBOT (p<0.05) according to the univariate and multivariate analysis. No adverse effects related to treatment were reported, only one patient was excluded due to claustrophobia. CONCLUSIONS: Hyperbaric oxygen therapy is an effective and safe treatment for the management of hematuria due to radiological cystitis secondary to radiotherapy. A better response was observed in patients with a lower degree of hematuria and those who could be administered a greater number of sessions.

OBJETIVO: Evaluación la eficacia de la oxigenoterapia hiperbárica (OHB) en el tratamiento de la cistitis rádica hemorrágica (CRH) postradioterapia.MATERIAL Y MÉTODO: Estudio retrospectivo que incluyó a los pacientes diagnosticados de hematuria secundaria a CRH postradioterapia pélvica desde enero de 2005 hasta enero del 2017 tratados con OHB. Se recogieron variables demográficas y clínicas. Se efec-tuó un análisis estadístico descriptivo, univariante y multivariante mediante regresión de Cox. El tratamiento se consideró eficaz cuando se produjo una remisión total o parcial de la hematuria en base a la escala del Grupo Oncológico de Radioterapia (RTOG). La respuesta parcial se definió como la presencia de hematuria grado 2 o menor tras el tratamiento. RESULTADOS: Se recogieron un total de 67 pacientes con una edad media de 68,6 años (39-87). Un 65,7% hombres y 34,3% mujeres. La RT fue administrada en el 64,2% de los casos por causa urológica, la más frecuente fue el cáncer de próstata. La dosis media de RT fue 75,24 Gy (45- 180). La media desde la RT hasta el tratamiento con OHB fue de 55,97 meses (4-300) y desde el inicio de la hematuria hasta el tratamiento de 11,3 meses (1-48). Se observó algún tipo de respuesta en 51 (76,1%) pacientes, siendo una respuesta total en el 50,7% y parcial en el 25,4% de los casos. Los pacientes con un grado de hematuria menor a 3, aquellos que recibieron más de 30 sesiones, y aquellos que no precisaron transfusión ni ingreso hospitalario, respondieron significativamente mejor al tratamiento (p<0,05), según el análisis univariante y multivariante. No fueron reportados efectos adversos relacionados con el tratamiento, solo un paciente fue excluido por claustrofobia. CONCLUSIONES: La terapia con OHB es una tratamiento efectivo y seguro para el manejo de la hematuria por CRH secundaria a radioterapia. Se observó una mejor respuesta en los pacientes con un menor grado de hematuria, en aquellos que recibieron mayor número de sesiones y que no precisaron transfusión ni ingreso hospitalario.

Effectiveness of hyperbaric oxygen therapy for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P < 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.

Intravesical Instillation of Kangfuxin Liquid Combined with Thrombin and Epidermal Growth Factor for Radiation-induced Hemorrhagic Cystitis in Patients with Cervical Cancer: A report of 34 cases.

This study aimed to assess the effectiveness and safety of intravesical instillation treatment of Kangfuxin liquid (KFL) combined with thrombin and epidermal growth factor (EGF) for radiation-induced hemorrhagic cystitis (HC) in patients with cervical cancer. A total of 34 patients with radiation-induced HC of grade 2-4 were treated with intravesical instillation of KFL combined with thrombin and EGF until the complete disappearance of hematuria and lower urinary tract symptoms (LUTS). Gentamicin was added if white blood cells were detected and bacterial culture was positive in the urine. All patients were followed up for 2 years to evaluate the clinical efficacy and safety of the treatment regimen. Patients with and without recurrent hematuria (n = 3, 9% and n = 31, 91%, respectively) were completely recovered from hematuria and LUTS by intravesical instillation treatment for 6-22 days. No adverse event was reported during the treatment and the 2-year follow-up for all patients. Thus, intravesical instillation of KFL combined with thrombin and EGF is an effective and safe therapeutic regimen for radiation-induced HC of grade 2-4 in patients with cervical cancer.

The clinical research of 5 steps sequential method for whole treatment of hemorrhagic radiation cystitis in china.

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P<0.01). Conclusions: Our results show hemorrhagic radiation cystitis can be cured in 5 steps, and the 5 steps sequential method is welcomed and effective. Therapy efficacy depends on the number of steps adopted and the severity of hematuria.

Hyperbaric oxygen for radiation-induced cystitis: A long-term follow-up. / Oxígeno hiperbárico para la cistitis inducida por radioterapia: un seguimiento a largo plazo.

INTRODUCTION AND OBJECTIVES: Bladder complications may be seen in up to 12% of patients treated with pelvic irradiation. Hyperbaric oxygen therapy (HBOT) is an option for the management of radiation-induced hemorrhagic cystitis (RIHC). The aim of this study was to evaluate the efficacy of HBOT in radiation cystitis and to identify the predictive factors for a successful outcome. MATERIAL AND METHODS: We retrospectively reviewed 105 patients diagnosed with RIHC which were treated with HBOT between 2007 and 2016 in our institution. Patients received 100% oxygen in a multiplace hyperbaric chamber at 2.4atm for 80minutes. All patients fulfilled a questionnaire documenting symptom severity pre-HBOT and at the end of the follow-up period. RESULTS: After a median of 40 HBOT sessions, there was success rate of 92,4% in the control of hematuria. During our follow-up period (median of 63 months) 24,7% patients presented with recurrence of hematuria. The mean score of the questionnaire-assessed variables: dysuria, urinary frequency and hematuria, was significantly lower after the follow-up period (P<.05). Our data shows that the sooner HBOT is delivered after the first episode of hematuria, better response rates are achieved and lower recurrences concerning hematuria were registered (P<.05). No serious complications were observed. CONCLUSIONS: Our results support the safety and long-term benefits of HBOT on RIHC and other distressful bladder symptoms, which represents an expected improvement of quality of life in our patients.

Hyperbaric oxygen for refractory hemorrhagic cystitis after stem cell transplantation: case report.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (AHSCT) in both children and adults has been associated with significant morbidity and mortality. Early HC can occur within 48 hours of completing the chemotherapy conditioning regimen, is usually associated with agents such as cyclophosphamide, and generally resolves promptly. Late HC is commonly associated with BK and other viruses and can prove refractory to antiviral and supportive therapy. There are limited reports of hyperbaric oxygen (HBO2) therapy showing benefit for refractory HC cases. We describe our experience with salvage HBO2 for a 15-year-old male with refractory HC beginning one month post AHSCT and associated with BK virus. Despite supportive therapies including hyperhydration, forced diuresis, transfusions, intravenous and intravesical cidofovir, macroscopic hematuria persisted and resulted in post-obstructive acute renal failure, need for a suprapubic catheter, then bilateral percutaneous nephrostomy tubes. HBO2 was started two months after the AHSCT and one month after detection of BK viremia. In the week prior to starting HBO2 therapy the patient required transfusion with 25 units of red blood cells and seven units of platelets. After HBO2 was started his transfusion requirements progressively decreased, and he had return of renal function. He had no adverse effect from the HBO2. HBO2 therapy could thus be useful in controlling refractory HC after AHSCT.

Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: Systematic review of the recent literature.

The present study assessed the efficacy of hyperbaric oxygen therapy in reducing symptoms of radiation cystitis, a specific type of iatrogenic injury to the bladder, by systematic review of recent literature. The MEDLINE, Embase and Web of Science databases were searched using combinations of the terms "radiation," "cystitis" and "hyperbaric oxygen" to identify articles evaluating patients with radiation cystitis, treated with hyperbaric oxygen therapy. Only recent (≤10 years) original studies were included. Data were extracted and pooled in order to calculate descriptive weighted averages. Articles were evaluated on their level of evidence. A total of 20 papers were obtained, resulting in a cohort of 815 patients who were treated with hyperbaric oxygen therapy for radiation cystitis. Overall and complete response rates varied from 64.8% to 100% and 20% to 100%, respectively. The weighted average overall and complete response rates were 87.3% and 65.3%, respectively. Adverse events were observed in 9.6% of the patients, but permanent side-effects were rare. The most prominent limitations were high cost and low availability. Hyperbaric oxygen therapy is effective in the treatment of radiation-induced cystitis, with minimal adverse events, but low availability and high cost. At present, evidence is low; therefore, more prospective studies are required.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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.

Current management of radiation cystitis: a review and practical guide to clinical management.

INTRODUCTION: Haemorrhage is a frequent complication of radiation cystitis leading to emergency presentations in patients with prior pelvic radiation therapy. Standard initial patient management strategies involve resuscitation, bladder washout with clot evacuation and continuous bladder irrigation. Beyond this, definitive surgical treatment is associated with significant morbidity and mortality. Alternative less invasive management options for non-emergent haemorrhagic cystitis include systemic medical therapies, hyperbaric oxygen (HBO), intravesical therapies and laser ablation. However, evidence to support and compare treatment for haemorrhagic radiation cystitis is limited. METHODS: Herein, a literature search pertaining to the current management of haemorrhagic cystitis was conducted. RESULTS: In total, 23 studies were included in this review with 2 studies reviewing systemic therapy, 7 studies evaluating HBO therapy, 10 studies investigating a variety of intravesical therapies and the remaining 4 were relating to ablative therapies. Across these studies, the patient groups were heterogenous with small numbers and variable follow up periods. CONCLUSION: With evaluation of existing literature, this narrative review also provides a stepwise clinical algorithm to aid the urologist in treating patients presenting with complications associated with radiation cystitis.

Cancer survivorship issues with radiation and hemorrhagic cystitis in gynecological malignancies.

PURPOSE: Given that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options. METHODS: There are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature. RESULTS: Treatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed. CONCLUSIONS: In this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Scoping Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis.

PURPOSE OF REVIEW: To critically review and summarize existing literature assessing the effectiveness of hyperbaric oxygen therapy (HBOT) for the treatment of radiation-induced urologic injury. RECENT FINDINGS: Though 5 of the included 13 studies were published in the last 2-3 years, the only randomized controlled study was performed in 2012. Recent studies have confirmed the safety and efficacy of HBOT as well as identified risk factors for success vs. failure of HBOT for hemorrhagic radiation cystitis (HRC). Of the 602 patients that received HBOT for HRC, 84% had a partial or complete resolution. In the 7 studies that utilized RTOG/EORTC, 75% of patients saw an improvement in hematuria of at least one grade (out of possible 5 total). Of the 499 patients with documented follow-up, 14% experienced recurrence, with a median time to recurrence of 10 months (6 to 16.5 months).