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Care of the patient with interstitial cystitis: current theories and management.

Interstitial cystitis is a disease process that has only come into focus over recent years. Researchers are looking for a cause of this painful and frustrating disorder of the bladder, but currently, only theories exist. Nurses must understand the pathophysiology of the disease and the dysfunction of the bladder to educate and assist the patient in the management of this chronic process. This report provides the nurse with information and education on the symptoms, pathophysiology, nursing diagnoses, and potential treatment modalities.

Adult↗

Overrepresentation of point mutations in the Sp1 site of the non-coding control region of BK virus in bone marrow transplanted patients with haemorrhagic cystitis.

BACKGROUND: Haemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with reactivation of BK virus (BKV) manifested as BK viruria. However, it has been suggested that BKV reactivation alone is not responsible for HC, since BKV can be detected in the urine of 50-90% of all adult BMT patients. OBJECTIVES: In the present study, we analysed if BK viruses with specific mutations in the non-coding control region (NCCR) or in the region encoding the major capsid protein (VP1) were more frequently associated to the appearance of HC in BMT patients. STUDY DESIGN: The NCCR and the region encoding VP1 of BKV excreted in the urine from 25 BMT patients, 16 with and nine without HC, were sequenced by an ABI Prism Big Dye terminator cycle sequencing ready reaction kit. RESULTS AND CONCLUSIONS: A statistically significant (P=0.019) overrepresentation of C to G mutations within the NCCR Sp1 binding site was observed in 7/16 (43%) patients with HC (six cases at position 249 (P=0.035) and one case at position 251), as compared with 0/9 (0%) of the patients without HC. Major differences were not observed in the VP1 sequences of patients with and without HC. BKV WW and WWT-variants as well as BKV subtype I were most commonly encountered in both groups of patients. In conclusion, C to G point mutations, within the BKV NCCR Sp1 binding site, were significantly more common in patients with HC, suggesting that these mutations may be indicative for the clinical diagnosis of HC and could influence the virulence of the virus.

BK Virus↗

BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist.

BACKGROUND: Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77-90% of all adult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, a significant overrepresentation of C-->G mutations in the Sp1 binding site in the non-coding control region (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients. OBJECTIVES: We aimed to investigate if this mutation resulted in excessive BKV excretion in HC patients. STUDY DESIGN: A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients with HC, with and without the mutations, as well as from patients without HC. RESULTS: Quantification of BKV was successful in 18 of 21 urine patients (six with and six without C-->G mutations) and six patients without HC. A mean of 3.0 x 10(6) BKV copies/microl was detected in urine samples of HC patients with C-->G mutations, compared to a mean of 1.5 x 10(6) BKV copies/microl in HC patients without C-->G mutations and a mean of 1.0 x 10(6) BKV copies/microl in patients without HC. The obtained differences were however not statistically significant, due to one individual non-HC patient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HC groups expressed 1 x 10(6) copies/microl or more, only one of the samples in the non-HC group contained a virus quantity higher than 5 x 10(5) copies. CONCLUSIONS: Although we could not confirm that the C-->G mutations in the Sp1 site of BKV were responsible for an increased viral load in patients with HC, our data suggest that levels of BKV above 10(4) copies/microl may indicate a risk for HC.

BK Virus↗

Human polyomavirus BK (BKV) load and haemorrhagic cystitis in bone marrow transplantation patients.

Several observations suggest an association between long-lasting haemorrhagic cystitis (HC) in bone marrow transplantation (BMT) recipients and human polyomavirus BK (BKV) reactivation, but no conclusive evidence has been obtained so far. The amount of BKV measured in the urine of BMT patients during an episode of HC was compared with that detected in the urine of BMT patients without HC and of immunocompetent individuals in order to better assess the association of BKV reactivation with HC. For this purpose a quantitative competitive PCR was developed. The application of this assay to clinical samples allowed us to distinguish asymptomatic reactivation both in healthy individuals and in immunocompromised patients from reactivation associated with HC, in almost all cases. Low levels, below the sensitivity of the quantitative assay, were shown in asymptomatic healthy individuals and in about 50% of immunocompromised patients. A significantly higher viral load than in the urine of asymptomatic immunocompromised patients was detected in the urine of patients with HC. These data strengthen the hypothesis that BKV reactivation can cause, together with other factors, the majority of late HC in BMT recipients as well as in patients treated for acute refractory lymphoblastic leukemia.

Adolescent↗

Atypical presentations of emphysematous cystitis.

Emphysematous cystitis is an uncommon infection of the bladder with the formation of carbon dioxide either within the bladder or within its wall. It is commonly seen in women and those with poorly controlled diabetes mellitus, in association with some form of urinary stasis and obstruction. The clinical features are very varied and the outcome is often unpredictable. Radiography may reveal a radiolucent line around the bladder wall or gas within the bladder. Occasionally, computed tomography scans are required to help in the diagnosis due to their atypical presentation with acute abdominal pain. Herein, we report three patients with such a condition who were treated with favourable outcomes. Of the three patients, two had to undergo exploratory laparotomy due to their initial presentations with acute abdomens.

Aged↗

Cystitis cystica glandularis masquerading as a bladder tumor.

A young man admitted with complaints of painless paroxysmal gross hematuria was found to have bilateral vesical masses involving the bladder base, trigone and ureteric orfices. Urine cytology and AFB were negative. Transurethral resection of the bladder mass was carried out and the histopathology suggested cystitis cystica glandularis. The literature regarding this entity has been reviewed and the differential diagnosis discussed.

Adult↗

Polypoid cystitis unrelated to indwelling catheters: a report of eight patients.

Since polypoid cystitis (PC) is generally caused by indwelling catheter use, in order to evaluate the patients with PC unrelated to a intravesical catheter, a retrospective analysis of the records of the Pathology Department of Turgut Ozal Medical Center was performed and this revealed 8 patients. Mean age of the 2 female and 6 male patients was 48 years (28 to 70). None of the patients had bacterial growth in urine cultures. All cases were diagnosed incidentally by radiologic and cystoscopic examinations in the evaluation of different conditions, such as hematuria, ovarian abscess, bladder carcinoma, erectile dysfunction, neurogenic bladder, benign prostate hyperplasia and unexplained dysuria. At the beginning, all patients were diagnosed mistakenly as bladder carcinoma. The definitive diagnosis was made after histopathologic examinations of transurethrally resected specimens. Patients were followed for 6 months to 2 years after first diagnosis. No recurrence was established during follow-up. The final urologic examinations which were done currently, were normal. In conclusion, PC is a benign lesion and should be considered in the differential diagnosis of transitional cell carcinoma of the bladder.

Adult↗

Angiogenesis inhibition by angiostatin, endostatin and TNP-470 prevents cyclophosphamide induced cystitis.

Angiogenesis, the induction of vessel growth is involved in numerous physiological and pathological processes. While the anti-tumor effect of angiogenesis inhibitors has been extensively investigated in malignant tumors, there is very little information on the effect of angiogenesis inhibitors on inflammation induced angiogenesis. In this report, we utilized a murine model of acute chemically induced cystitis to investigate the ability of three different angiogenesis inhibitors, angiostatin, endostatin and TNP-470, to inhibit the angiogenesis stimulated by this injury. We demonstrate herein, that prophylactic application of the angiogenesis inhibitors led to a significant reduction of each of the inflammatory parameters that were measured. We conclude that anti-angiogenic therapy with angiostatin, endostatin and TNP-470 inhibits inflammation associated angiogenesis induced in this model. We also propose that anti-angiogenic agents may serve as a valuable addition to a standard cyclophosphamid chemotherapy regimen to help reduce the chemotherapy-related side effects while potentially adding an anti-tumor effect.

Angiogenesis Inhibitors↗

Eosinophilic cystitis induced by penicillin.

A 30-year-old woman developed classic symptoms of painful bladder disease and eosinophilic cystitis as an adverse effect of penicillin for abdominal actinomycosis. The symptoms were reversible after stopping penicillin.

Actinomycosis↗

Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Adolescent↗

Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study.

A prospective randomised study was carried out to compare the effect of mesna (2-mercaptoethane sulphonate sodium) with that of forced diuresis in preventing cyclophosphamide induced haemorrhagic cystitis in marrow transplant recipients. Sixty-one consecutive BMT recipients were randomised for treatment with forced diuresis or mesna. The incidence of macroscopic haematuria was significantly lower in the mesna treated group (chi 2 = 4.03, P less than 0.05). No specific side effects of mesna were detected. The lymphopenia induced by cyclophosphamide in the aplastic recipients was similar in the mesna and forced diuresis groups suggesting that mesna has no effect on the lymphocytotoxic activity of cyclophosphamide, although 6 out of 7 episodes of graft failure documented in the study occurred in mesna treated patients. As a result of this study our present policy is to use mesna in all BMT recipients but to continue careful documentation of the incidence of graft failure.

Adolescent↗

The management of interstitial cystitis: an update.

Treating interstitial cystitis (IC) is one of the greatest challenges facing physicians and other health care providers who manage patients with this condition. The symptoms of urinary frequency and urgency, dysuria, and chronic pelvic pain characterize IC, but it is the debilitating pelvic pain associated with IC that is most difficult to control. The pathophysiology of IC pain is poorly understood, but is thought to be a complex entity including nociceptive, visceral, and neuropathic components. There are currently no universally effective therapies available. Oral treatments, however, are frequently used, including nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, gabapentin, and pentosan polysulfate, all of which have shown varying degrees of efficacy. Recognition that IC pain is multifactorial, and probably has a neuropathic component, has led to the use of some of these agents, previously prescribed for other neurologic conditions associated with chronic pain. Intravesical and surgical options are also available, which expands the armamentarium for those who treat pain secondary to IC. Treating IC requires managing all of the symptoms of this disease. This review aims to cover standard and novel treatment options, while concentrating on the management of pain.

Cystitis, Interstitial↗

Treatment of adenovirus-associated haemorrhagic cystitis with ganciclovir.

We report a 47-year-old bone marrow transplant recipient with haemorrhagic cystitis caused by adenovirus successfully treated with ganciclovir. This is the first report on the use of ganciclovir for the successful treatment of adenoviral infection. Shell vial culture may be more sensitive than conventional culture in the detection of adenovirus in such patients.

Adenoviridae↗

High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine.

Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus). HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia. HC occurring before day 100 was significantly associated with a reduction in long-term survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34+ progenitors or CD3+ cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series.

Adenoviridae Infections↗

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↗

Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis.

The role of amifostine in the prevention of cyclophosphamide-induced hemorrhagic cystitis (HC) was evaluated in the rat model. Urinary bladders from control rats that received no drugs (group I) were compared with those from rats receiving cyclophosphamide alone at a dose of 150 mg/kg (group II), and two other groups receiving amifostine at 100 mg/kg (group III) and 200 mg/kg (group IV), 15 min prior to cyclophosphamide. Bladders were assessed macroscopically and histologically at 24 h and after 7 days. All the animals that received cyclophosphamide alone developed severe HC. On the basis of the scores of macroscopic and histologic changes, animals that received amifostine showed excellent uroprotection. Only 2/6 rats in group III and 1/6 rats in group IV developed mild HC at 24 h. None of the rats in either of these groups showed any evidence of HC at 7 days. It is concluded that amifostine protects the urothelium against cyclophosphamide-induced HC.

Amifostine↗

Haemorrhagic cystitis: incidence and risk factors in a transplant population using hyperhydration.

Haemorrhagic cystitis (HC) is the syndrome of haematuria and symptoms of lower urinary tract irritability in the absence of bacterial infection. We report a low incidence of HC (18.2%) in 681 haemopoietic stem cell transplant patients, using a prophylactic regimen of hyperhydration and forced diuresis. The incidence of grade 3-4 disease is 3.4%. There was a marked difference in incidence between allogeneic and autologous transplant populations, 24.2% vs. 3.5% (P<0.0005). Busulphan conditioning, acute GVHD, interstitial pneumonitis and use of methotrexate and cyclosporin immune suppression were associated with significantly increased incidence of HC in the allogeneic population. This may reflect the numerous factors that contribute to the greater immunosuppression and consequent increased risk for HC in allogeneic transplantation.

Cystitis↗

Intravesical rhGM-CSF for the treatment of late onset hemorrhagic cystitis after bone marrow transplant.

In the present study, we assessed the clinical effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in the treatment of refractory, grade III-IV hemorrhagic cystitis (HC) in six patients who underwent bone marrow transplantation (BMT). These were four males and two females, aged 24-40 years (median age 30.5 years). All received allogeneic BMT from HLA-identical siblings after preparation with busulfan-cyclophosphamide. HC was evident 24. 5 days (range 15-33 days) after BMT. Median duration of HC before treatment was 5 days (range 4-9 days). Treatment consisted of intravesical instillation of rhGM-CSF (400 microg) for 3 consecutive days. A complete response was observed in three patients, the other three showed a partial response. Median time to achieve response was 36 h (range 0.2-72 h). Hematuria was controlled after the first (two patients), second (two patients) or third (two patients) dose of intravesical rhGM-CSF. Patients were discharged from the hospital 10. 5 days (range 3-41 days) after treatment. All patients have been followed for up to 10 months and none have required further treatment. No systemic or bladder side-effects have been observed. Although our results indicate that intravesical instillation of rhGM-CSF is effective in the treatment of HC, a phase II clinical trial, including a larger series of patients, is needed.

Adult↗