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[Hyperbaric oxygen therapy in the successful treatment of two cases of radiation-induced hemorrhagic cystitis].

Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant lesions often might be incurable and there have been established no definitive treatment. We experienced 2 cases with radiation-induced severe hemorrhagic cystitis refractory to conventional therapy. The treatment with hyperbaric oxygen to control hematuria was performed and obtained successful results. Gross hematuria was disappeared and cystoscopic figure was remarkably improved. No remarkable side-effect was observed in both patient. This experience suggested that hyperbaric oxygen could be considered the primary treatment for patient with radiation-induced hemorrhagic cystitis instead of usual treatment.

Aged↗

Continuous subcutaneous administration of mesna to prevent ifosfamide-induced hemorrhagic cystitis.

Hemorrhagic cystitis is a major potential toxicity of ifosfamide that can be prevented by administering mesna along with the cytotoxic agent. Mesna is generally administered by the intravenous route, although experience with oral delivery of the drug has increased. The continuous subcutaneous administration of mesna has the advantage of not requiring intravenous access. In addition, subcutaneous delivery of the neutralizing agent will not be associated with the risk of inadequate urinary mesna concentrations, such as in a patient taking oral mesna who experiences severe ifosfamide-induced emesis and is unable to absorb the drug. Limited clinical experience with continuous subcutaneous mesna administration suggests it is a safe, practical, and economic method of drug delivery that permits ifosfamide to be administered successfully in the outpatient setting.

Administration, Oral↗

Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis.

Hemorrhagic cystitis (HC) is a known complication of allogenic BMT. We report a case of a 28-year-old female with CML in chronic phase, which was treated with a matched unrelated donor (MUD) transplant, complicated by hemorrhagic cystitis on day +42 after the transplant. Adenovirus was isolated from the urine and she was treated with ribavirin, 1 g twice a day for 8 days. We report the use of Amicar (E-aminocaproic acid), 2.5 g solution as bladder instillation to treat the intractable hematuria.

Adenoviridae Infections↗

Endoscopic neodymium:YAG laser treatment of radiation-induced hemorrhagic cystitis.

Hemorrhagic cystitis is a debilitating complication of radiation therapy for pelvic malignancy. Forty-two such patients with intractable hematuria underwent endoscopic Nd:YAG laser coagulation under local anesthesia between January 1990 and July 1992. The laser power was kept at < or = 30 W and the pulse duration < or = 3 s. Control of bleeding was achieved in 39 patients after one sitting and in 2 patients after two sittings of laser treatment. There were no complications of the procedure and recurrence of bleeding was not seen in any of the patients achieving CR at a mean follow-up period of 14 months. With modifications in the safety guidelines, we recommend laser treatment as the initial procedure of choice in patients with hemorrhagic radiation cystitis.

Adult↗

Prevention and treatment of hemorrhagic cystitis.

Hemorrhagic cystitis is a syndrome associated with certain disease states as well as exposure to drugs, viruses, and toxins. It manifests as diffuse bleeding of the endothelial lining of the bladder. Treatment includes intravesical, systemic, and nonpharmacologic therapies, all of which have advantages and disadvantages.

Alkylating Agents↗

Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis.

Severe hemorrhagic cystitis developed in 6 children after marrow transplantation, 3 of whom had a viral etiology. All 6 patients received instillations of prostaglandin E1 directly into the bladder and 5 of the 6 had complete resolution of hematuria. This finding contrasts with our previous experience with severe hemorrhagic cystitis, particularly the type due to a viral infection, persisting in the face of numerous bladder manipulations. We encourage the use of this nontoxic treatment to gain further information regarding its effect on the bladder epithelium. The mechanism of action remains completely unknown.

Administration, Intravesical↗

Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis.

AIM: Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. METHODS: Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.

Animals↗

Evaluation of effects of chitosan in preventing hemorrhagic cystitis in rats induced by cyclophosphamide.

Hemorrhagic cystitis is a common problem following cyclophosphamide or radiation therapy. Chitosan has been shown to be an effective hemostatic agent and promoter of wound healing in animal experiments. We evaluated the safety and efficacy of intravesical chitosan in an animal model of cyclophosphamide cystitis. Hemorrhagic cystitis was induced in female F344 rats by intraperitoneal cyclophosphamide, 100 mg/kg. Chitosan solution (0.3 ml) was instilled intravesically on day 1 (Group 1), on days 1, 3, and 5 (Group 2), or 1 hour after the administration of cyclophosphamide (Group 3). The rats in group 4 were treated with chitosan diluent on day 1 after cyclophosphamide, and the rats in group 5 received intravesical chitosan without cyclophosphamide. Sequential examination revealed decreased mortality and lower incidences of severe bladder bleeding, necrosis and inflammation in Group 3. Treatment delayed until after the appearance of the cystitis, especially repeated treatments, appeared to make the cyclophosphamide-induced changes worse. Used within 1 hour of cyclophosphamide administration, before the cystitis develops, chitosan seemed to have the possibility to inhibit the appearance of hemorrhagic cystitis. In addition to the changes in the bladder, severe changes occurred in the kidneys secondary to cyclophosphamide.

Administration, Intravesical↗

Cystotomy, temporary urinary diversion and bladder packing in the management of severe cyclophosphamide-induced hemorrhagic cystitis.

Severe hemorrhage from cyclophosphamide-induced cystitis sometimes requires aggressive open management when conventional endoscopic and intravesical therapies have failed. We present 2 patients with intractable hematuria who were managed by open cystotomy, temporary urinary diversion via external ureteral stents, and continuous postoperative bladder packing with gauze and hemostatic agents. Both patients had a dramatic improvement in the hematuria immediately postoperatively and 1 with prolonged followup has no urological disability. We suggest that this procedure be considered for management of severe hemorrhagic cystitis as an alternative to more aggressive surgical therapies, such as formal urinary diversion with cystectomy.

Acute Disease↗

Treatment of radiation-induced hemorrhagic cystitis with laparoscopic cystoprostatectomy.

Hemorrhagic cystitis can occur 6 months to 10 years after pelvic irradiation. Various palliative treatment alternatives may be unsuccessful in the management of severe hemorrhagic cystitis, so that in rare cases radical surgery will be the last resort.A 77-year-old man with persistent bleeding due to hemorrhagic cystitis after radiotherapy for prostate cancer was initially treated with conservative measures. All of these treatment methods were unsuccessful. His condition deteriorated and became life-threatening. As a last resort, laparoscopic cystoprostatectomy and mini-laparotomy ileal conduit diversion were successfully performed with no intraoperative or postoperative complications. To our knowledge, this is the first report on laparoscopic cystoprostatectomy for a patient with previous radiotherapy to the pelvis.

Aged↗

Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen.

PURPOSE: Hemorrhagic cystitis can occur 6 months to 10 years after pelvic radiation therapy with moderate to severe persistent rates of hematuria as 3% to 5% after radiotherapy for pelvic malignancies. Current treatment modalities for hemorrhagic cystitis include oral and intravenous agents, intravesical therapy and selective embolization of the hypogastric arteries. Hyperbaric oxygen therapy is now a widely accepted treatment option for radiation induced hemorrhagic cystitis. We assess the efficacy of hyperbaric oxygen for treatment of hemorrhagic cystitis. MATERIAL AND METHODS: From May 1988 through March 2001, 62 patients with radiation induced hemorrhagic cystitis were treated with hyperbaric oxygen at our institution. Followup ranged from 10 to 120 months. The primary pathological conditions were prostate cancer (81%) and bladder cancer (10%). Mean patient age was 70 years (range 15 to 88). Mean time between completion of radiation therapy and onset of hematuria was 48 months (range 0 to 355). Patients received an average of 33 hyperbaric oxygen treatments (range 9 to 68). RESULTS: Of the 62 patients treated information on 57 was available for analysis. Of the 57 patients (86%) 49 experienced complete resolution or marked improvement of hematuria following hyperbaric oxygen treatment. Of the 8 patients who did not improve 4 received fewer than 40 hyperbaric oxygen treatments and 7 prematurely terminated treatment (medical co-morbidities 4, claustrophobia 2, temporary resolution of symptoms 1). CONCLUSIONS: Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis is an efficacious treatment modality for patients in whom other forms of management have failed.

Adolescent↗

Hemorrhagic cystitis complicating bone marrow transplantation.

Hemorrhagic cystitis is a potentially serious complication of high-dose cyclophosphamide therapy administered before bone marrow transplantation. As standard practice at our institution, patients who are scheduled to receive a bone marrow transplant are treated prophylactically with forced hydration and bladder irrigation. In an attempt to obviate the inconvenience of bladder irrigation, we conducted a feasibility trial of uroprophylaxis with mesna, which neutralizes the hepatic metabolite of cyclophosphamide that causes hemorrhagic cystitis. Of 97 patients who received standard prophylaxis, 4 had symptomatic hemorrhagic cystitis. In contrast, two of four consecutive patients who received mesna uroprophylaxis before allogeneic bone marrow transplantation had severe hemorrhagic cystitis for at least 2 weeks. Because of this suboptimal result, we resumed the use of bladder irrigation and forced hydration to minimize the risk of hemorrhagic cystitis.

Academic Medical Centers↗

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats.

BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.

Amifostine↗

Safety and cost of hyperhydration for the prevention of hemorrhagic cystitis in bone marrow transplant recipients.

Hemorrhagic cystitis is a major cause of morbidity after bone marrow transplantation. Traditional methods of prevention have included mesna (2-mercaptoethane sodium sulfonate) and bladder irrigation. We report the use of hyperhydration as an alternative to these prophylactic measures. One hundred consecutive patients who underwent autologous or allogeneic bone marrow transplantation received high dose cyclophosphamide with hyperhydration using 5% dextrose normal saline at the rate of 250 ml/h and furosemide to maintain a urine output of >150 ml/h. Seventy-one of these patients also received high dose cyclophosphamide as mobilization chemotherapy. There were no episodes of hemorrhagic cystitis following mobilization chemotherapy. The incidence of hemorrhagic cystitis after transplant conditioning was 7% with 2 patients developing clinically significant hemorrhagic cystitis; one was a severe episode. The cost of hyperhydration was US$ 20 per course as opposed to US$ 1,500 per course for mesna, based on acquisition costs at our institution. We conclude that hyperhydration is a safe, inexpensive means of preventing hemorrhagic cystitis associated with high dose cyclophosphamide in bone marrow transplant recipients.

Adult↗

Risk factors for severe hemorrhagic cystitis following BMT.

Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graft-versus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P < 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna.

Acute Disease↗

Percutaneous nephrostomy for treatment of intractable hemorrhagic cystitis.

Six patients with severe hemorrhagic cystitis unresponsive to traditional localized therapy were treated with percutaneous nephrostomy for diversion of urine. Bladder hemorrhage ceased in 3 patients, decreased in 2 and was unchanged in 1. In 1 patient with profound thrombocytopenia perirenal hematoma developed as a result of the nephrostomy placement but this complication was self-limited and did not require surgery. Our experience with these 6 patients indicates that nephrostomy diversion is safe and effective in most cases of hemorrhagic cystitis refractory to traditional, nonoperative therapy. Percutaneous urine diversion may obviate the need for surgical urinary diversion in patients who have intractable hemorrhagic cystitis.

Cystitis↗

Cyclophosphamide hemorrhagic cystitis requiring urinary diversion.

Hemorrhagic cystitis secondary to cyclophosphamide is a well recognized and unique urologic complication of this widely used agent. Cessation of the drug and supportive care are usually sufficient for management but refractory cases are difficult to treat and potentially life-threatening. A review of the pathology and treatment of this disorder is presented with specific reference to a patient requiring urinary diversion.

Adult↗

Prevention of cyclophosphamide-induced hemorrhagic cystitis.

The occurrence of hemorrhagic cystitis with the use of high-dose cyclophosphamide is thought to be a toxic effect of cyclophosphamide metabolites directly on the bladder mucosa. To decrease both the concentration of metabolites in contact with the bladder mucosa and the time of such contact, a regimen of diuresis and frequent voiding or catheter drainage was instituted in patients at risk for the development of hemorrhage. Prior to institution of this regimen, 8 of 97 patients experienced massive clot-producing hemorrhage, three-quarters of whom died as a direct result of such hemorrhage. Subsequent to use of this regimen, only 1 of 198 patients experienced this degree of hemorrhage. Although this is only a phase II study, the dramatic decrease in the incidence of hemorrhage strongly suggests the efficacy of this regimen in decreasing the potential morbidity associated with cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide↗