Cystitis In Children Research Articles

Ultrasonography in the diagnosis of hemorrhagic cystitis - a complication of bone marrow transplantation in pediatric oncology patients.

ObjectiveThe aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of hemorrhagic cystitis following bone marrow transplantation in children.Material and methodsThe study involved an analysis of clinical material and the results of imaging tests performed in 334 patients who underwent hematopoietic cell transplantation. Ultrasonographic findings in 42 patients with hemorrhagic cystitis were analyzed in detail. The ultrasound images served to assess the severity of hemorrhagic cystitis and the results were compared with the clinical assessment of the disease on the Droller scale, as well as the laboratory and endoscopic tests.ResultsIn the studied group of patients hemorrhagic cystitis following allogeneic transplantation was diagnosed in 12.5% cases. 73.8% patients received transplants from unrelated donors, 26.2% – from compatible siblings. The study revealed a higher incidence of hemorrhagic cystitis in children above 10 years of age. Grade 3 according to the Droller was diagnosed in 42.9%, grade 2 – in 30.9%, grade 4 – in 14.3%, and grade 1 – in 11.9% patients. The number of ultrasound examinations depended on the clinical symptoms, severity, duration and co-occurrence of other complications following the transplantation and was within the 1–15 range (average: 4.6). Grades 3 and 4 were related to the poor clinical condition of the patients and to their longer hospitalization. During this period there was an increased risk of renal malfunction and acute renal failure, post-inflammatory narrowing of the ureters, hydronephrosis, and in grade 4 the fibrosis of the bladder with reduced bladder capacity. Analyses demonstrated a significant correlation between the ultrasound image of the bladder wall and the clinical severity.ConclusionsUltrasound with Doppler options remains the primary diagnostic tool in the evaluation of hemorrhagic cystitis, and is useful in terms of its diagnosis, determination of the severity, and monitoring of the treatment.

Sulfolane (a metabolite of busulfan) Levels Could Predict Occurrence Of Hemorrhagic Cystitis In Children Receiving Busulfan Based Myeloablative Conditioning Before Hematopoietic Stem Cell Transplantation

Background One of the complications of myeloablative conditioning regimen with busulfan (BU) and cyclophosphamide (CY) in children undergoing hematopoietic stem cell transplantation (HSCT) is the occurrence of hemorrhagic cystitis (HC). Pathophysiology of HC involves multiple factors, such as damage to the bladder's transitional epithelium and the endothelium of blood vessels by BU, CY and their metabolites, viruses, bacterial infections, or other disease processes. It is well established fact that damage to the urothelium is the initial step during pathogenesis of HC. Though it is known about acrolein (metabolite of CY) contribution to HC development, the role of BU or its metabolites is not yet known completely. We recently developed an analytical method for sulfolane (Su) quantification, a water soluble metabolite of BU. Using this method we explored the relation of Su levels in plasma with HC before day 30 post-transplant, in 39 children (20 females, 19 males) receiving BU-CY conditioning prior to HSCT. Methods Hospital ethics committee approved the study, and all patients or their parents have signed the informed consent. Out of 39 patients 16 were diagnosed with nonmalignant disease. BU was administered in 16 dose infusions, with each infusion lasting two hours for every six hours. Bone marrow and cord blood were graft sources in 18 and 21 patients, respectively. Twenty patients had HLA–matched donor. HC was defined as the presence of hematuria (both microscopic and macroscopic) for more than a week from the initiation of the conditioning regimen up to 30 days post-transplant. All patients received MESNA as prophylaxis for HC. Plasma from patients collected before dose 7 and after dose 9 infusions of BU was used for measuring Su levels using gas-chromatography. Plasma levels of Su adjusted to cumulative BU dose up to Su level measurements (upto dose 6 for before dose 7 levels, upto dose 9 for after dose 9 levels) in mg/kg were used in the analysis. Mann-Whitney U test was used to analyze the relation of Su levels (ng/mL//mg/kg) and HC. A receiver–operator characteristic curve (ROC) for Su levels was plotted to show the trade-off in sensitivity versus 1- specificity rates for HC, as the cut-off of the test was shifted from low to high. Two sided p values were represented and probability at 0.05 was considered as statistically significant. Cumulative incidences of HC were estimated using Kaplan-Meier curves and log-rank test was used to compare the difference between groups divided based on cutoff defined in ROC curves, in univariate analysis. Univariate cox-regression was used to estimate hazard ratios with 95% confidence intervals. Results The overall cumulative incidence of HC was 20.5 %. We observed higher Su levels before dose 7 (mean±SD; 48.3±11.2 vs. 35.1±15.3 – p=0.02) and after dose 9 (40.5±9.6 vs. 30.9±14.4 – p=0.03) in patients diagnosed with early HC (n=8) compared to those with no HC (n=31-Figure 1A, Figure 1B), respectively. Cutoff values of 49.44 and 36.28 were chosen in ROC analysis for Su levels before dose 7 and after dose 9, respectively with better sensitivity and specificity to diagnose HC (Figure 1C). Patients with Su levels above the cutoff value defined (before dose 7, 41.7 %; after dose 9 42.9 %) had higher incidence of HC compared to those below the cutoff (before dose 7, 11.0 %; after dose 9, 8.0 %) at both dose levels (Figure 2A, Figure 2B). Age and Weight were also correlated with the incidence of HC, with higher incidence in patients older than 10 years, and weighed above 30 kg. Higher levels of Su correlated with the weight and age of the patients. Out of 8 individuals diagnosed with HC, 6 were detected positive for BK virus and one patient was positive for JC virus. Conclusion Higher plasma Su levels might also explain availability of Su and its hydroxyl metabolite in bladder to cause damaging effect similar to that of acrolein. We hypothesize that formation of Su is related to the volume of liver and enzyme activity which is usually correlated with weight and age of the patient. These levels might also predict the extent for acrolein formation, and might serve as surrogate marker to identify patients predisposed to HC. A functional study to elucidate the effect of Su on bladder urothelium is underway at our laboratory to understand its role in pathogenesis of HC. Disclosures: No relevant conflicts of interest to declare.

Urological management (medical and surgical) of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation

Aim: Haemorrhagic cystitis (HC) is uncommon and in its severe form potentially life threatening complication of Haematopoietic stem cell transplantation (HSCT) in children. We present our single centre experience in the urological management of this clinically challenging condition. Patients and Methods : Fourteen patients were diagnosed with BK-Virus HC in our centre. The mean age at diagnosis was 8.8 years (range, 3.2-18.4 years). The mean number of days post-BMT until onset of HC was 20.8 (range, 1 – 51). While all patients tested urine positive for BKV at the clinical onset of HC, only four patients had viral quantification, with viral loads ranging from 97,000 to >1 billion/ml. 8 patients had clinical HC. Ten patients experienced acute GVHD (grade I: 6 patients, grade II: 3 patients, grade 4: 1 patient). Results: Four patients received medical management for their HC. Treatments included hyperhydration, MESNA, blood and platelet transfusion, premarin and oxybutynin (Table 6). Two patients received both medical and surgical management which included cystoscopy with clot evacuation, bladder irrigation and supra-pubic catheter insertion. One patient received exclusive surgical management. Seven patients were treated conservatively. Conclusion : There is limited available evidence for other potential therapeutic strategies highlighting the need for more research into the pathophysiology of HSCT-associated HC. Commonly used interventions with possible clinical benefit (e.g. cidofovir, ciprofloxacin) still require to be evaluated in multi-centre, high-quality studies. Potential future preventative and therapeutic options, such as modulation of conditioning, immunosuppression and engraftment, new antiviral and anti-inflammatory and less nephrotoxic agents need to be assessed. --------------------------- Cite this article as: Vasdev N, Davidson A, Harkensee C, Slatter M, Gennery A, Willetts I, Thorpe A.Urological management (medical and surgical) of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation. Int J Cancer Ther Oncol 2013; 1 (1):01013. DOI : http://dx.doi.org/10.14319/ijcto.0101.3

Hemorrhagic cystitis in children treated with alkylating agent cyclophosphamide: The experience of a medical center in Taiwan

Hemorrhagic cystitis is a common complication with chemotherapeutic alkylating agents. We investigated the possible prognostic factors of cyclophosphamide-induced hemorrhagic cystitis in children. Medical records of children (< 18 years old) with cyclophosphamide-related hemorrhagic cystitis were collected retrospectively from January 2000 to December 2010 in a tertiary care center. We also prospectively enrolled children (< 18 years old) with cyclophosphamide treatment. The retrospective study consisted of 23 patients whose median age was 11 years. The median day of onset time was 1 day after cyclophosphamide usage. The hemato-oncological diseases included acute leukemia (39.1%), lymphoma (13%), blastoma (13%), sarcoma (13%), aplastic anemia (13%), and others (8.7%). Patients who received bone marrow transplantation (BMT) had significantly longer duration of hemorrhagic cystitis than those who did not receive BMT (p < 0.05). Serum uric acid, checked prior to and after the onset of hemorrhage cystitis, was significantly lower after the development of hemorrhagic cystitis (p < 0.05). In the prospective study, 11 children were enrolled with a median age of 5 years. The urinary nitrite/nitrate and 8-iso-prostaglandin F2α levels increased significantly after cyclophosphamide usage (p < 0.05). Alteration serum uric acid level and BMT could be indicators for severe hemorrhagic cystitis. The elevated levels of urinary nitrite/nitrate and 8-iso-prostaglandin F2α may indicate the essential roles played by nitric oxide syntheses and reactive oxidative stress in cyclophosphamide-induced hemorrhagic cystitis. These findings may help clinicians formulate a better strategy for treating cyclophosphamide-induced hemorrhagic cystitis.

Progress in diagnosis and treatment of eosinophilic cystitis in children

Eosinophilic cystitis(EC) is a kind of bladder proliferation disease and rather rare in children.The pathological character shows invasion of huge amounts of eosinophil granulocytes in the total bladder wall.Although it has unknown etiology, but it is widely believed to be involved in allergy.It can appear at any age with a higher incidence in male.Since it was first reported in 1960, there are a total of more than 300 patients reported, about 70 of them are children.The major clinical manifestations are urinary frequency, suprapubic pain during miction, gross or microscopic hematuria, dysuria, nocturia and so forth.Some patients with increased eosinophils in the peripheral blood.It is essential to examine blood routine, urine routine, imaging tests and cystoscopy and defining diagnosis depends on histopathologic biopsy.The self-limiting of EC in children is much stronger.The main therapies for EC are application of corticosteroids, antihistamines and so forth, while feasible operation should be treated when severe complications appear or the disease progress. Key words: Eosinophilic cystitis; Diagnosis; Treatment; Urodynamic study

Treatment of Chronic Cystitis in Children

Chronic inflammatory processes of the urinary bladder’s wall dominate in the structure of urologic diseases in children, but the issue of their treatment still remains very acute. Despite the use of modern methods of treatment, children with chronic recurrent cystitis constitute a significant part of the total number of hospitalized patients (19 to 21%). In recent years quite many morphological studies of the bladder’s mucosa during inflammatory diseases were held. However, the mechanism that leads to the damage of the urothelium in chronic cystitis and factor that determines the type of metaplasia during inflammation of the bladder are unclear. Endoscopic examination, in some cases, does not allow differentiating inflammatory from tumor-like lesions of the mucosa. Destructive lesions of the bladder’s mucosa occur during exacerbation of chronic inflammation or severe, far gone acute inflammation. Therefore, conducting endovesical biopsy is necessary for clarifying forms of chronic cystitis and identifying urothelial hyperplasia or dysplasia and is critical in the diagnosis of diseases of the urinary bladder. It is still unclear under what endoscopic and morphological forms of recurrent cystitis in children neurogenic bladder disorders are more frequent and for what form of recurrent cystitis most pronounced neurogenic bladder dysfunctions are more likely to occur. The nature and extent of neurogenic disorders in children with various forms of recurrent cystitis in the late periods after antireflux surgeries remain unexplored.

BK-virus-associated Hemorrhagic Cystitis in Children After Hematopoietic Stem Cell Transplantation

BK-virus-induced hemorrhagic cystitis (BK-HC) is a serious complication in children undergoing hematopoietic stem cell transplantation (HSCT). Data of BK-HC in children undergoing HSCT are still limited. To describe the epidemiology, clinical course, and outcome of children with BK-HC after HSCT. The medical records of all children aged 0 to 20 years, who underwent HSCT at Schneider Children's Medical Center between 2000 and 2008 and were diagnosed with BK-HC, were reviewed for demographic, clinical, and microbiological data. Patients in whom BK-HC had developed were compared with patients in whom it did not. Seventeen children (5.3%) acquired BK-HC at 10 to 180 days after HSCT (mean, 57 d); 9 had grade 3 to 4 disease. Bleeding lasted for 4 to 42 days (mean, 14). All patients but 1, who died of unrelated causes, recovered. Follow-up ranged from 6 to 91 months (mean, 35 months). Acute myeloid leukemia, use of cyclophosphamide in the conditioning regimen, unrelated donor, and older age were associated with the development of hemorrhagic cystitis (HC). The incidence of BK-HC in children after HSCT is relatively low. Its rate of successful resolution is very high. Further prospective studies are required to determine optimal therapy.

BK-Virus Associated Hemorrhagic Cystitis in Children Following Haematopoietic Stem Cell Transplantation. A Six Years Experience in One Pediatric Bone Marrow Transplantation Center

Hemorrhagic cystitis (HC) is a common complication after haematopoietic stem cell transplantation (HSCT). Urotropic viruses may cause late-onset HC (BK virus {BKV}, adenovirus, CMV) associated with severe immunosuppression. Treatment is mainly symptomatic. The incidence and severity of HC depends on primary disease, pre-transplant viral status, conditioning, immunosuppressive drugs, source of graft and Graft-versus-Host Disease.

993 Comparison of Paraclinical Findings in Acute Pyelonephritis and Cystitis in Children

Background: Urinary tract infection is a common disease in children requiring immediate diagnosis and treatment. The aim of this study was to compare the paraclinical findings in acute pyelonephritis and cystitis in children. Methods and materials: In this case-control study a group of sixty children with first symptomatic UTI and an abnormal DMSA scan (acute pyelonephritis) were compared with another sixty children with UTI and a normal DMSA scan (cystitis). This study was enrolled in Qazvin children hospitatal affiliated to Qazvin University of Medical sciences in Qazvin (Iran) in 2007. Results: There was no significant difference between two groups according to data obtained for WBC, urinalysis, type of microorganism, and sonography (p>0.05) nevertheless, regarding the findings for ESR, CRP, and vesicoureteral reflux, a significant difference demonstrated (p< 0.05). The sensitivity, specificity, and the accuracy of our data were unreliable. Conclusion: Our study revealed that none of the laboratory and imaging findings tested was individually capable of locating the site of urinary tract infection, thus the performance of DMSA renal scanning to diagnose acute pyelonephritis is of prime necessity.

Late-Onset Hemorrhagic Cystitis in Children after Hematopoietic Stem Cell Transplantation for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir

Little is known about late-onset hemorrhagic cystitis (HC) in children, its relationship to BK virus, and treatment with cidofovir (CDV) following hematopoietic stem cell transplantation (HSCT). We prospectively investigated BK virus reactivation in children who underwent HSCT from a matched related donor for thalassemia or sickle cell anemia following busulfan-cyclophosphamide-based conditioning regimens and analyzed risk factors for development of HC and its treatment with CDV. Grade 2-4 HC occurred in 30 patients with a cumulative incidence of 26% (95% confidence interval [CI] = 18%-34%). The cumulative incidences of BK viruria and viremia were 81% (95% CI = 69%-89%) and 28% (95% CI = 18%-40%), respectively. Multivariate analysis revealed that use of antithymocyte globulin (ATG) (hazard ratio [HR] = 10.5; P = .001), peak BK viruria >100,000 copies/mL (HR = 6.2; P = .004), and grade II-IV acute graft-versus-host disease (HR = 5.3; P = .007) were predictive factors for HC. Nineteen patients with HC were given CDV at 1.5 mg/kg/day 3 times a week, or 5 mg/kg/week. The median duration of therapy was 27 days (range, 21-180 days), and a median of 9 doses were given (range, 6-22). All patients had a complete clinical response (CCR), and 69% had a microbiological response at 4 weeks. Eleven patients with BK virus-related HC receiving supportive care also had CCR. The median duration of HC in these patients was similar to that in patients treated with CDV. None of the patients with HC cleared BK viruria when CCR was achieved. We conclude that late-onset HC is more prevalent in children with sustained high BK viruria who are treated with ATG or who develop graft-versus-host disease. Randomized clinical trials are urgently needed to better define the role of CDV in treating BK virus-related HC.

Late-Onset Hemorrhagic Cystitis in Children After Hematopoietic Stem Cell Transplantation (HSCT) for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir (CDV).

Abstract 1133Poster Board I-155 BackgroundHemorrhagic cystitis (HC) is a significant cause of morbidity after allogeneic HSCT. BK virus infection has been associated with development of HC after HSCT, however most studies detected the virus at the time of cystitis, therefore not allowing estimation of the relationship between BK reactivation and HC. Furthermore little is known about development of late-onset HC in children following HSCT, its association with BK virus and treatment with Cidofovir. Therefore we prospectively investigated BK virus reactivation in pts receiving HSCT from HLA-identical related donors, risk factors for development of HC and treatment efficacy with CDV. Patients and Methods117 pts with thalassemia (n=107) and sickle cell anemia (n=10) with median age of 9 years (range, 1.7-17) were enrolled in this study. All pts received BUCY ± Thiotepa containing conditioning regimens. GVHD prophylaxis was cyclosporine and short MTX ± Thymoglobulin-ATG (in 26 pts). Before August 2006 qualitative BK-PCR was performed on urine samples in pts with HC. Since then we prospectively performed qualitative and quantitative PCR on blood and urine samples collected before conditioning regimen and weekly thereafter until at least 100 days post transplant in 64 pts. The quantitative BK virus assay was performed with Real Time Alert Q-PCR-Nanogen kit. Risk factors for the development of HC were evaluated on univariate and multivariate analysis using cumulative incidence curves and Competing risk regression analysis respectively. The cumulative incidence of HC was estimated considering death without HC as competing event. Nineteen pts with HC were given CDV at 1.5 mg/kg/day 3 times/week (n= 10) or 5 mg/kg/week (n=9). Results60 out of 64 pts (94%) had at least 1 positive and 52 of them (81%) 2 or more positive samples for BK viruria. 34 pts (53%) showed al least 1 and 18 of them (28%) 2 or more positive samples for BK viremia. The number of viral copies varied from <556 to >55 million copies. Median time to platelet engraftment was 23 days (range,8-163) and median number of platelets at onset of HC was 81×109/l (range, 2-274 ×109/l). Thirty pts (26%) developed clinically significant (grade 2 to 4) HC within 1 year after HSCT at a median of 38 days (range, 13- 114). All pts with HC had BK viruria. Coexisting viral infections were found in 3 pts: CMV in 2 and adenovirus in 1. The severity of HC was grade 2 in 24 pts, grade 3 in 2 and grade 4 in 4. The 4 pts with grade 4 HC had moderate or severe hydronephrosis along with partial ureteral obstruction which necessitated ureteral stent placement. The cumulative incidence of grade 2 or 3-4 HC was 21%(95% CI 13%-28%) and 5%(95%CI 2%-10%) respectively. In univariate analysis the use of ATG, peak BK viruria, GVHD and age >8 years were associated with HC. Multivariate analysis confirmed the prognostic importance of ATG (HR=10.5; p=0.001), peak BK viruria >100,000 copies (HR=6.2; p=0.004), and acute GVHD (HR=5.3; p=0.007), but not age for HC development. The cumulative incidence of HC in pts who had 2 adverse factors was 64%, compared with 31% (or 53%) and 10 % who had either one (GVHD or ATG) or none of these factors (p<0.0001). However, there were 10 pts who had at 2 or more time points BK viruria >6 millions copies without developing HC. With a median follow-up among survivors of 35 months (range, 5-61) HC did not have a significant impact on survival.Both dosing schedules of CDV were well tolerated and no cases of dose-limiting nephrotoxicity were observed. The median duration of HC was 17 days (range 9-53). The median duration of therapy was 27 days (range,21-180) with a median of 9 doses given (range,6-22). All pts had clinical response but only 6 pts (32%) had microbiological response at 2 weeks after therapy. None of these patients cleared BK viruria when a complete clinical response was achieved. The median time from clinical response to BK viruria clearance was 74 days (range, 14-176). Ten pts with grade 2 and one with grade 3 HC occurred before prospective trial of CDV had spontaneous resolution of HC. The median duration of HC in these pts was similar to those treated with CDV. ConclusionBK viruria is common after HSCT and high viral load is a risk factor for HC. However, even higher-level BK replication alone is not sufficient to cause HC. Coexisting factors such as the use of ATG and GVHD significantly contribute to the development of HC. Cidofovir may have some activity against BK virus-related HC, although our data showed that spontaneous resolution of HC could also occur. DisclosureNo relevant conflicts of interest to declare DisclosuresOff Label Use: Cidofovir as antiviral drug for treatment of BK virus-related hemorrhagic cystitis.

Prevention and management of BK‐virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation – a systematic review and evidence‐based guidance for clinical management

Haemorrhagic cystitis (HC) is a common and, in its severe form, potentially life-threatening complication of Haematopoietic stem cell transplantation (HSCT) in children. Recent data indicate an important role of BK virus reactivation during the time of maximal post-transplant immune suppression in the pathogenesis of late-onset HC. Treatment of HC is mainly symptomatic and often frustrating. To give clinicians guidance on prevention and treatment options and their backing by scientific evidence, we have systematically assessed the available literature and devised evidence-based guidelines. Our comprehensive review demonstrates that evidence for the most commonly used interventions (such as cidofovir, oestrogen, hyperbaric oxygen, bladder instillation with formalin, alum salts or prostaglandin) is very limited. Some of these interventions also carry significant risks. Higher level evidence exists only for 2-mercaptoethane sodium (MESNA) and hyperhydration as a preventative intervention, and for systemic recombinant Factor VII as a treatment to stop acute haemorrhage. Further high-quality studies are required to establish effective and safe prevention and treatment options for HC.

Risk factors and treatment of hemorrhagic cystitis in children who underwent hematopoietic stem cell transplantation

A retrospective cohort of 163 children with 171 hematopoietic stem cell transplantation (HSCT) performed during Mar. 1992-Dec. 2005 were analyzed to evaluate the incidence, risk factors, management, and outcome of hemorrhagic cystitis (HC). Fourteen patients (8.2%) developed HC (6 boys, median age 6.6 years) at 0-166 days after HSCT (median 25 days), and lasted for 3-96 days (median 26 days). Older age at transplant (median 11.0 vs. 6.4 years, P = 0.013), allogeneic transplant (OR = 4.4, P = 0.02), cyclophosphamide-containing conditioning (OR = 4.87, P = 0.008), moderate-to-severe acute graft-versus-host disease (GVHD) (OR = 3.56, P = 0.025) and hepatic GVHD (OR = 3.62, P = 0.017) were associated with higher risks of HC in univariate but not multivariate analyses. While estrogen was ineffective in most patients, intravesical formalin, which was used in five patients, was found to be a very effective yet safe treatment for intractable HC. Patients with HC had longer hospital stay (median 175 vs. 88 days, P = 0.004). HC resolved after treatments in all cases but eight of the 14 patients subsequently died of other complications of HSCT. In conclusion, HC is a serious complication of allogeneic HSCT. Treatment with intravesical formalin appears effective and safe and can be considered early in severe HC to reduce the risk of morbidity and mortality.

Eosinophilic cystitis in children

目的 分析儿童嗜酸性膀胱炎的临床及CT表现.方法 对9例经病理证实的儿童嗜酸性膀胱炎(7例)及嗜酸性肉芽肿性膀胱炎(2例)的临床及CT表现进行研究.结果 临床上均伴有血尿、膀胱刺激征、排尿困难和腹痛等症状.影像学上,4例表现为膀胱壁结节状或局限性增厚,其中2例为嗜酸性肉芽肿性膀胱炎,其余5例表现为膀胱壁弥漫性不均匀增厚.结论 嗜酸性膀胱炎的影像学及临床表现与膀胱肿瘤易于混淆,病变的活检定性对于作出正确诊断及制定相应治疗方案是必不可少的步骤。

Eosinophilic cystitis: Successful long-term treatment with montelukast sodium

We report a rare case of eosinophilic cystitis in a 6-year-old boy who presented with irritative voiding symptoms, peripheral eosinophilia, and a bladder mass initially visualized on ultrasonography. Cystoscopy and transurethral biopsy confirmed the diagnosis. Complete resolution of his symptoms occurred within 1 week of corticosteroid use and the x-ray findings improved within 6 weeks. At 6 months of follow-up, the patient continued to require a leukotriene receptor antagonist (montelukast sodium) despite several attempts to discontinue its use. We propose that eosinophilic cystitis in children who present with peripheral eosinophilia will often require long-term treatment.

Risk factors and treatment of hemorrhagic cystitis in children after hematopoietic stem cell transplantation

Hemorrhagic cystitis (HC) is one of the common complications of hematopoietic stem cell transplantation (HSCT), which causes significant pain, prolongs hospitalization, and occasionally results in renal failure and death. This study aimed at investigating the incidence, risk factors, and outcome of HC in children post umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT). From October 1998 to June the clinical records of 53 pediatric patients (aged 2-18 years with median age of 7.5 years) in our HCST center who underwent UCBT (n = 37) and PBSCT (n = 16) were retrospectively analyzed. Thirty out of 53 patients were diagnosed as hereditary hemolytic anemia (56.6%), and the others as haematological malignancies (43.4%): of whom 8 had acute lymphoblastic leukemia, 12 acute myeloid leukemia, 2 chronic myeloid leukemia and 1 non-hodgkin lymphoma. Conditioning regimen varied according to disease and clinical status, however based on cyclophosphamide (CTX, 120-200 mg/kg) and busulphan (BU, 12-16 mg/kg) in the cohort. Total body irradiation (TBI) or total lymphoid irradiation was added in 7 patients respectively. The patients were divided into regular treatment group (RTG) with 15 cases who received hyperhydration, alkalinizing, diuresis and Mesna during CTX infusion and prostaglandin E1 (PGE1) group (PEG) with 38 cases who received hyperhydration, alkalinizing, diuresis and Mesna plus prostaglandin E1 (0.03 microg/kg.h). The risk factors of HC were examined by univariate and multivariate analysis. In all, 11 of the 53 transplanted patients developed HC (21%) with a median onset time of day +15 (rage day +2 - +25). HC was classified as early in 4 (36%) and late in 7 (64%), and scored as grade Iin 2 cases (18%), grade II in 4 (36%) and grade III in 5 (46%). There was no significant difference between RTG and PEG in the incidence of HC, however, the incidence was much higher in the group of patients who were > or = 6 years old, positive group of graft-versus-host disease (GVHD) and group of cytomegalovirus (CMV) infection than that in the group of patients who were < 6 years of age (32% vs. 8%, P < 0.05), negative group of GVHD (35% vs. 7%, P < 0.05) and CMV non-infected group (62% vs. 13%, P < 0.05), respectively. Furthermore, by multivariate analysis, > or = 6 years old (OR = 3.53, P < 0.05) and CMV infection (OR = 4.31, P < 0.05) were significant risk factors for HC. Three of 11 patients were treated with bladder irrigation. All patients recovered from HC in a median 12.8 days (range 2-53 days). Older age (> or = 6 years) as well as CMV infection were the risk factors of HC. Both hyperhydration and Mesna were effective in preventing HC, while addition of PGE1 could not reduce the incidence of HC. The prognosis of HC in children post HSCT was satisfactory.

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Hemorrhagic Cystitis in Children Undergoing Bone Marrow Transplantation: A Putative Role for Simian Virus 40

Late-onset hemorrhagic cystitis (HC) is a well-known severe complication of bone marrow transplantation (BMT), both in adults and in children. Protracted postengraftment HC is associated with graft-versus-host disease and viral infections, mainly caused by BK virus (BKV) or adenovirus (AV). This study investigated whether simian virus 40 (SV40) DNA sequences can be detected in specimens from pediatric patients affected by severe postengraftment HC. The clinical diagnosis of HC was made in 7 of 28 BMT children. DNA from peripheral blood mononuclear cells (PBMC) and urine sediment cells and supernatants was analyzed by polymerase chain reaction (PCR) for human cytomegalovirus (HCMV), AV, BKV, JC virus (JCV), and SV40. DNA filter hybridization and sequencing was carried out in SV40-positive samples. SV40 footprints were detected in two of seven cases of HC. Specific SV40 DNA sequences were detected by PCR and by filter hybridization both in urine and in PBMC samples at the HC onset and during the follow-up. The DNA sequencing proved that the amplicons belonged to the SV40 wild-type. Urine samples of the two HC cases tested negative by cell cultures, PCR, or both for HCMV, BKV, JCV, and AV. The detection of SV40 DNA sequences suggest that this simian polyomavirus could be involved, at least in some cases, in the HC occurring in children after BMT.

Incidence and treatment of hemorrhagic cystitis in children given hematopoietic stem cell transplantation: a survey from the Italian association of pediatric hematology oncology-bone marrow transplantation group.

The purpose of this multicenter study was to assess the incidence and the treatment of hemorrhagic cystitis (HC) in 1218 pediatric patients, with a mean age of 10.8 years, who underwent hematopoietic stem cell transplantation (HSCT). In all, 44 patients (3.6%) developed HC a median 23 days after HSCT. The incidence of HC was higher in allogeneic than in autologous HSCT recipients (P=0.0001). Of the 44 patients, 37 (84%) recovered from HC in a median 30 days (range 3-100); the other seven children died while still suffering from HC. Hyperbaric oxygen therapy (HOT) achieved significantly better results than prostaglandin therapy (P=0.02) in the treatment of grade II-III HC. By multivariate analysis, age <96 months and allogeneic HSCT were significantly associated with the occurrence of HC: P=0.008 and 0.013, respectively. After a median follow-up of 5.75 years, the 5-year survival of patients who did or did not develop HC was: 43 vs 52%, P=0.03, respectively. This study indicates that age and type of HSCT are factors predisposing to HC in children given HSCT and demonstrates the promising role of HOT in a conservative approach to HC treatment.

Single-dose intramuscular ceftriaxone for the treatment of uncomplicated cystitis in children and adolescents

Abstract The purpose of this randomized, open-label, controlled, clinical trial was to determine whether intramuscular (IM) ceftriaxone is as effective as multiple-dose oral trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of cystitis in children and adolescents. Outpatients 1 to 19 years of age with cystitis were randomly allocated to receive either a single dose of IM ceftriaxone or oral TMP-SMX twice daily for 10 days. Nine of 27 patients who received ceftriaxone 500 mg failed to respond to treatment at 4 to 82 days after enrollment and the start of treatment; 6 of 22 patients who received TMP-SMX failed to respond to treatment at 7 to 168 days (intent-to-treat analysis; P =0.99). Five of 10 patients who received ceftriaxone 250 mg failed to respond to treatment at 18 to 99 days; this arm of the study was discontinued because of the high failure rate. Results of this study suggest that ceftriaxone 500 mg and TMP-SMX were equally effective in the treatment of simple cystitis in children and adolescents.