Evaluation of HIF-1α and VEGF-A expression in radiation-induced cystitis: A case-control study

ABSTRACT The standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy. Once the bladder receives part of the radiation, a typical inflammatory condition that configures radiation-induced cystitis may develop. Chronic radiation-induced cystitis is commonly characterized by the bladder new submucosal vascularization, which is typically fragile and favors hematuria. The current study aims to investigate if Hypoxia-Induced Factor (HIF-1α) and its transcriptional target Vascular Endothelial Growth Factor A (VEGF-A) could be a primary pathway leading to increased submucosal vascularization. HIF-1α and VEGF-A mRNA levels in bladder core biopsies from CC patients treated with radiotherapy versus untreated (non-irradiated) patients were analyzed using a droplet digital polymerase chain reaction technology. Gene expression results showed that HIF-1α and VEGF-A had no significant differences between bladder samples from patients previously irradiated and untreated patient samples. However, a direct relationship between the degree of late morbidity and the expression of HIF-1α and VEGF-A has been demonstrated. Despite the lack of statistical significance precludes a definitive conclusion, the data presented herein suggests that further studies investigating the role of HIF-1α in bladder neovascularization in radiation-induced cystitis are highly recommended.

Analysis of the Risk Factors for Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors affecting hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).@*METHODS@#The clinical data of 153 patients underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were selected and retrospectively analyzed. The incidence, median time and treatment outcome of HC should be observed. Multivariate analysis was used to observe the risk factors of HC in patients, including sex, age, diagnosis, disease status before transplantation, transplantation type, ATG and CTX in the pretreatment scheme, stem cell source, neutrophil and platelet implantation time; CMV, EBV and BKV infection, and acute graft-versus-host disease(aGVHD).@*RESULTS@#Among 153 patients underwent allogeneic hematopoietic stem cell transplantation, 25 (16.34%) patients had HC, the median occurance time was 31 days, all patients achieved complete remission after treatment, no bladder irritation and bladder contracture were left. The results of univariate and multivariate Logistic regression analysis showed that the type of transplantation, ATG, CMV viremia before treatment, aGVHD (r=1.036, 3.234, 3.298 and 2.817, respectively) were the independent risk factors of HC.@*CONCLUSION@#The urinary BKV detections in the patients with HC are positive, mainly occured during the period from day +13 to days +56. HLA haplotype, pretreatment including ATG, and CMV viremia, and aGVHD are the independent risk factors for HC after allo-HSCT.

Gas surrounding the urinary bladder in emphysematous cystitis

ABSTRACT We report a rare case of emphysematous cystitis in a 66-year-old woman with a history of diabetes mellitus. The predisposition of diabetes mellitus and infection of gas-forming bacteria is considered to precede the manifestation of emphysematous cystitis. The present recommended diagnosis test is computed tomography, which have definite value in the evaluation of gas accumulation in bladder wall, or an air-fluid level in bladder.

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.

Hemorrhagic Cystitis Requiring Bladder Irrigation is Associated with Poor Mortality in Hospitalized Stem Cell Transplant Patients

Purpose: To evaluate the overall prognosis of post-stem cell transplant inpatients who required continuous bladder irrigation (CBI) for hematuria. Materials and Methods: We performed a retrospective analysis of adult stem cell transplant recipients who received CBI for de novo hemorrhagic cystitis as inpatients on the bone marrow transplant service at Washington University from 2011-2013. Patients who had a history of genitourinary malignancy and/or recent surgical urologic intervention were excluded. Multiple variables were examined for association with death. Results: Thirty-three patients met our inclusion criteria, with a mean age of 48 years (23-65). Common malignancies included acute myelogenous leukemia (17/33, 57%), acute lymphocytic leukemia (3/33, 10%), and peripheral T cell lymphoma (3/33, 10%). Median time from stem cell transplant to need for CBI was 2.5 months (0 days-6.6 years). All patients had previously undergone chemotherapy (33/33, 100%) and 14 had undergone prior radiation therapy (14/33, 42%). Twenty-eight patients had an infectious disease (28/33, 85%), most commonly BK viremia (19/33, 58%), cytomegalovirus viremia (17/33, 51%), and bacterial urinary tract infection (8/33, 24%). Twenty-two patients expired during the same admission as CBI treatment (22/33 or 67% of total patients, 22/28 or 79% of deaths), with a 30-day mortality of 52% and a 90-day mortality of 73% from the start of CBI. Conclusions: Hemorrhagic cystitis requiring CBI is a symptom of severe systemic disease in stem cell transplant patients. The need for CBI administration may be a marker for mortality risk from a variety of systemic insults, rather than directly attributable to the hematuria.

A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with the GreenLight™ XPS Laser

The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH), for the treatment of radiation-induced hemorrhagic cystitis.

A new problem in inflammatory bladder diseases: Use of mobile phones!

Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor. .

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. .

Caso clínico: cistitis enfisematosa asociada a hidronefrosis secundaria / Emphysematous cystitis: Report of one case

We report a 53 year-old woman with type 2 diabetes mellitus and hypertension, presenting with progressive abdominal pain lasting three weeks, associated with lower abdominal swelling and fever. Clinical examination showed a large increase in abdominal volume, contraction of extracellular compartment, and signs of severe sepsis. Computed tomography showed an over-distended bladder with severe wall and luminal pneumatosis and bilateral hydronephrosis. The diagnosis was of emphysematous cystitis associated to hydronephrosis. Urine and blood cultures were positive for multi-susceptible Escherichia coli. Clinical evolution was favorable after 6 weeks of ceftriaxone and urinary catheter use. Emphysematous cystitis is a rare clinical entity, with an associated mortality of 7%. Known predisposing factors are older age, female gender and presence of diabetes. Microbiological agents most frequently involved are Escherichia coli and Klebsiella pneumoniae (80% of cases). Medical treatment is preferred and is based on urinary tract decompression with a bladder catheter, and prolonged broad spectrum antimicrobial therapy.

Diverticulitis vesical: reporte de un caso y revisión de la literatura / Bladder diverticulitis: case report and literature review

Se presenta un caso de diverticulitis vesical en un paciente de 60 años con antecedente de obstrucción crónica al tracto de salida vesical (estenosis uretral), quien consulta por dolor pelviano inespecífico. Por lo anterior se realiza Resonancia Magnética (RM) de pelvis, que demuestra la presencia de un divertículo vesical de pared engrosada con cambios inflamatorios, los que comprometen además, la grasa peri-vesical. Este divertículo había sido detectado en RM pelviana un año antes. Se comenta el caso clínico, sus hallazgos a la RM y revisión de la literatura...

We report a case of bladder diverticulitis in a 60 years old patient with a history of chronic lower urinary tract obstruction (urethral stricture), who consulted for nonspecific pelvic pain. Pelvic magnetic resonance imaging (MRI) was obtained, demonstrating the presence of a bladder diverticulum with a thick wall and inflammatory changes involving the perivesical fat. The diverticulum had been detected on pelvic MRI a year earlier. We discuss the clinical case, the MRI findings and a review of the literature....

Effect of lycopene on cyclophosphamide-induced hemorrhagic cystitis in rats

Cylophosphamide is used alone or in combination with other drugs for treatment of neoplastic diseases. Hemorrhagic cystitis is a major potential toxicity and dose limiting side effect of cyclophosphamide. The aim of this study was to evaluate the effects of lycopene compared with some antioxidants for the prevention of cyclophosphamide induced hemorrhagic cystitis in rats. In this study, male Sparague-Dawley rats divided into 17 groups of six animals. Group 1 received saline [10 ml/kg, i.p] as normal control, group 2 received cyclophosphamide [200 mg/kg, i.p] as a single dose, groups 3-10 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [200 and 400 mg/kg, i.p], grape seed extract [500 mg/kg i.p] and lycopene [0.1 and 0.5 mg/kg, i.p] alone. Groups 11-17 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg, i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [400 mg/kg, i.p], grape seed extract [500 mg/kg, i.p] and lycopene [0.1 and 0.5 mg/kg, i.p], 5 minutes before, and 2 and 6 hours after administration of 200 mg/kg cyclophosphamide. Pathological and biochemical analysis was evaluated 24 hours after cyclophosphamide administration Mesna and N-acetylcysteine resulted in some but not full protection against cyclophosphamide toxicity compared to the controls. Lycopene [0.1 and 0.5 mg/kg] was efficient in protecting the bladder from cyclophosphamide induced hemorrhagic cystitis. However, dithiotheritol, L- carnitine and grape seed extract did not prevent hemorrhagic cystitis. Our results suggest that pre and co- treatment of lycopene [0.1 and 0.5 mg/kg] with cyclophosphamide may have therapeutic potential to inhibit the hemorrhagic cystitis by cyclophosphamide

comparison study of the effects of Echinacea purpurea ethanolic extract and Mesna on cyclophosphamide indueed macroscopic fetal defects in rats

There are some reports that the teratogenic effects of cyclophosphamide [CPA] can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Echinacea purpurea extract is antioxidative and immunomodulator drug. Mesna [Sodium 2-mercaptoethane sulfonate] is used for decreasing side effects of CPA, especially hemorrhagic cystitis. In this study, we compared the prophylactic effects of mesna and Echinacea extract on teratogenic effects of CPA. This study was performed on 32 pregnant rats that were divided into 4 groups. The first group [control group] received normal saline and the other groups received CPA [15 mg/kg intraperitoneally] on 13th day of gestation. Mesna and E. purpurea extracts were administrated at doses of 100 and 400 mg/kg by IP injection, respectively, along with it and 12 hr later, after CPA injection. Rats were dissected on day 20 of gestation, embryos harvested and after determination of gross malformations they were stained by Alizarin red-Alcian blue method. Cleft palate incidence was 38.46, 30.77 and 14.28% in fetuses of rats that received only CPA, CPA with mesna and CPA with Echinacea extract, respectively. In addition, skeletal anomalies incidence including limbs, vertebra, sternum, and scapula defects were decreased by Echinacea extract. E. purpurea has significant effect on preventing CPA-induced malformations and better prophylactic effect than mesna on cases like CPA-induced cleft palate

El bacilo de Calmette-Guérin como inmunomodulador en el cáncer de vejiga / The bacillus Calmette-Guérin as immunomodulator in bladder cancer

The bacillus Calmette-Guérin (BCG) is regarded as the most successful immunotherapy against superficial bladder carcinoma recurrences to date. BCG intravesical therapy for superficial bladder cancer has shown its efficacy and advantage over classical therapeutic strategies. This efficacy is based on complex and long lasting immune activation. The initial step is the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacteria surface with fibronectin in the bladder wall. Granulocytes and other immunocompetent mononuclear cells became attracted to the bladder wall and a cascade of proinflammatory cytokines sustains the immune response. In the bladder wall a largely TH1 based cytokine milieu and granuloma-like cellular foci are established. Within this scenario, the most important effector mechanisms might be the direct antitumor activity of interferons and the cytotoxic activity of NK cells. Current treatment consists of an induction phase of 6 weeks and a maintenance dose schedule of 3 weeks every three months up to 36. The majority of patients present adverse events related to dose administration due to bladder inflammatory response and on only a few ocassions, there are mayor complications like granulomatous prostatitis. Among all the neoplasms only in superficial bladder cancer the BCG is proved to be effective.

El bacilo de Calmette-Guérin (BCG) es considerado como la inmunoterapia más exitosa en contra del carcinoma de vejiga superficial recidivante hasta la fecha. La terapia intravesical con el BCG para el cáncer superficial de vejiga ha mostrado su eficacia y ventaja sobre otras estrategias terapéuticas; esta eficacia está basada en una compleja y larga duración de la activación inmunológica. El paso inicial es la unión de la micobacteria al urotelio, la cual depende de la interacción con la fibronectina de la bacteria con la fibronectina del urotelio. Los granulocitos y otras células mononucleares inmunocompetentes son atraídos hacia la pared vesical, así activando una cascada inmunológica a través de secreción de diversas citocinas, quienes estimulan a las células asesinas naturales (NK) activadas por el BCG, las cuales son capaces de diferenciar células neoplásicas y del epitelio urinario normal. En la pared vesical se encuentra un medio ambiente de citocinas principalmente del tipo TH1 y se forman focos celulares similares a granulomas. Dentro de este escenario los mecanismos efectores más importantes parecen ser la actividad antitumoral directa de los interferones y la actividad citotóxicas de las células NK. El tratamiento actual consiste en la administración intravesical del bacilo en una primera fase de inducción de seis semanas y posteriormente dosis de mantenimiento cada tres meses hasta los 36 meses. La mayoría de los pacientes presentan efectos adversos locales secundarios a la reacción inflamatoria y en un porcentaje muy pequeño se presentan complicaciones mayores como prostatitis y orquiepididimitis granulomatosa. De entre todas estas neoplasias sólo en el cáncer superficial de vejiga se han demostrado resultados satisfactorios con el empleo del BCG.

Etiological study on cystitis glandularis caused by bacterial infection / 华中科技大学学报（医学）（英德文版）

To study the relationship between bacterial infection and the etiology of cystitis glandularis, 36 female Wistar rats were divided into 3 groups. No intervention was given to the rats in the blank group. NS was infused into the bladder of the rats of the control group, and solution containing E. coli was injected into the bladder of experimental group. Three months later, tissue samples of bladder were collected and observed visually and under light microscope. The results showed that tissues of the blank group were normal; one sample in the control group showed Brunn's nests and cystitis cystica, and 10 in the experimental group had the change of cystitis glandularis. Compared to the blank and control group, samples in the experimental group showed significant change (P0.05). It is concluded that bladder instillation of E. coli can induce cystitis glandularis, which confirms that infection is the cause of cystitis glandularis.

Co-occurrence of emphysematous cystitis and emphysematous myositis in type 2 diabetes.

Emphysematous cystitis (EC) and emphysematous myositis (EM) are rare disorders and concurrent occurrence of both in a patient with type 2 diabetes has not been reported previously. We report a patient who presented with pneumaturia and later with pain in thigh and diagnosed of both concurrently.

Clinical investigation on the correlation between lower urinary tract infection and cystitis glandularis / 华中科技大学学报（医学）（英德文版）

In order to study the association between lower urinary tract infection and cystitis glandularis (CG), 120 cases of CG were diagnosed by cystoscopic biopsy in the suspicious foci of the bladder. Among them, 72 cases were subjected to bacterial counting culture of urine and microscopic examination of urinary sediment, and 60 cases to fluorescence quantitative polymerase chain reaction (FQ-PCR) assay to detect HPV, CMV and HSV DNA in urine samples. In the 72 cases of CG, the positive rate of bacterial counting culture of urine was 15.3% (11/72), and gray zone rate was 18.1% (13/72). 31.9% (23/72) patients were positive in bacterioscopy of urinary sediment. There was statistically significant difference as compared with the control group (P0.05). It was concluded that the genesis of CG was closely correlated with the chronic lower urinary tract infection, especially caused by Esch coli.

Hemorrhagic Cystitis Following Allogeneic Hematopoietic Cell Transplantation

We conducted a retrospective study to investigate the incidence, risk factors, and clinical features of hemorrhagic cystitis (HC) following allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients who developed HC after allo-HCT were identified from the HCT database of the Asan Medical Center and their medical records were reviewed. From December 1993 to August 2001, a total of 210 adult patients underwent allo-HCT. Fifty-one patients developed HC with a cumulative incidence of 25.7%. The median onset of HC was post-transplant day 24 (range, -2 to 474), and the median duration was 31 days (range, 8 to 369). Significant risk factors for HC by univariate analysis included diagnosis of chronic myelogenous leukemia (p=0.028), unrelated HCT (p=0.029), grade III-IV acute graft-versus-host disease (GVHD) (p<0.001), extensive chronic GVHD (p=0.001), and positive cytomegalovirus antigenemia between post transplant days 31 and 60 (p=0.031). Multivariate analysis showed that grade III-IV acute GVHD was the most important risk factor for the occurrence of HC after allo-HCT (odds ratio, 3.38; 95% CI, 1.36-8.39). Late-onset HC, which occurred beyond 3 weeks after allo-HCT, was more frequently associated with GVHD than earlyonset HC (p=0.007). Our data suggest that a portion of late-onset HC might be a manifestation of GVHD.