Cystectomy for Refractory Hemorrhagic Cystitis: Contemporary Etiology, Presentation and Outcomes Brian J. Linder, Robert F. Tarrell and Stephen A. Boorjian* From the Departments of Urology (BJL, SAB) and Health Sciences Research (RFT), Mayo Clinic, Rochester, Minnesota
Purpose: We evaluate the clinical presentation, management and outcomes of patients undergoing cystectomy for refractory hemorrhagic cystitis. Materials and Methods: We identified 21 patients with refractory hematuria treated with cystectomy at our institution between 2000 and 2012. Clot evacuation, bladder fulguration and bladder irrigation had failed in all patients before cystectomy. In addition, 45% of patients had received prior intravesical therapy (aminocaproic acid, alum or formalin), hyperbaric oxygen therapy (25%), nephrostomy tube placement for attempted urinary diversion (15%) and/or selective bladder angioembolization (5%). Results: Median patient age at surgery was 77 years (IQR 72, 80) and 81% (17 of 21) of patients were male. The most common etiology for hemorrhagic cystitis was prior radiation therapy for prostate cancer (17, 81%). Median time from receipt of radiation to cystectomy in these patients was 91 months (IQR 73, 125). Median ASAÒ (American Society of Anesthesiologists) score at cystectomy was 3 and median preoperative hemoglobin was 10.2 gm/dl. Median length of stay after cystectomy was 10 days (IQR 7, 19). Severe (Clavien grade III to V) complications were noted in 42% of patients (8 of 19) and the 90-day mortality rate in this cohort was 16% (3 of 19). With a median postoperative followup of 13 months (IQR 4, 21), the 1 and 3-year overall survival was 84% and 52%, respectively. Conclusions: Cystectomy for hemorrhagic cystitis is associated with a high risk of perioperative complications and mortality, consistent with the baseline clinical status of this patient cohort and, as such, should remain a last resort to control bleeding after failure of conservative measures.
Abbreviations and Acronyms BMI ¼ body mass index Accepted for publication June 9, 2014. Study received institutional review board approval. Nothing to disclose. * Correspondence: 200 First St. SW, Rochester, Minnesota 55905 (telephone: 507284-4015; FAX: 507-284-4951; e-mail: Boorjian. [email protected]).
Editor’s Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1896 and 1897.
Key Words: cystitis, hemorrhage, cystectomy, survival, radiotherapy
INTRACTABLE hematuria localized to the bladder, or hemorrhagic cystitis, is characterized by diffuse bleeding from the bladder mucosa. Numerous etiologies have been described as predisposing patients to hemorrhagic cystitis, although commonly the condition results from exposure to the oxazaphosphorine class of chemotherapy or pelvic radiotherapy.1 The severity of bleeding may vary from mild hematuria that resolves with conservative management such as
hydration and bladder irrigation, to transfusion dependent hemorrhage that is refractory to therapy.1 Algorithms for sequential management of such cases have been proposed,1 including escalating intervention from intravesical instillation therapies (such as alum or formalin) to hyperbaric oxygen and even bladder angioembolization. In the setting of continued bleeding, urinary diversion has been proposed, in part to eliminate the clot
0022-5347/14/1926-1687/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.06.030 Vol. 192, 1687-1692, December 2014 Printed in U.S.A.
www.jurology.com
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lysis effect of urokinase. While supravesical diversion with nephrostomy tube placement or conduit formation may be attempted, notably after diversion that leaves the bladder in situ, complications have been reported in up to 80% of patients, with almost half requiring hospital readmission and up to 35% requiring subsequent cystectomy.2,3 Thus, when diversion is being contemplated, the role of concomitant cystectomy merits consideration. However, a paucity of data exists regarding the outcomes of cystectomy in this setting, consisting of case reports.4,5 Given the established morbidity of cystectomy,6,7 documenting perioperative outcomes in this population remains relevant to inform discussion with patients regarding anticipated risks vs benefits of surgery. Indeed, decision making is often more challenging because most patients presenting with refractory bleeding from hemorrhagic cystitis are elderly and/or infirm. Therefore, we evaluated the clinical presentation, management and outcomes in a contemporary cohort of patients with hemorrhagic cystitis who underwent cystectomy for refractory disease in the acute setting and on a planned basis.
MATERIALS AND METHODS After receiving institutional review board approval we identified 21 consecutive patients who underwent cystectomy for hemorrhagic cystitis at the Mayo Clinic from 2000 to 2012. All patients were 18 years old or older and underwent cystectomy with urinary diversion after failure of more conservative measures. Cystectomy was performed by various surgeons using standard techniques. Patient charts were reviewed, and clinicopathological variables recorded included age at cystectomy, etiology for hemorrhagic cystitis, prior therapies used (ie bladder irrigation, clot evacuation, intravesical therapy, bladder angioembolization, urinary diversion), comorbid medical conditions, ASA score, operative time, length of postoperative hospitalization, perioperative (within 90 days of surgery) complications and overall survival. Postoperative complications were graded according to the Clavien-Dindo classification.8 In the event of sequential complications, all individual complications were recorded. However, only the highest grade of complication was reported. Clinical and demographic parameters as well as overall survival were also compared to a 1:1 matched cohort of patients undergoing cystectomy for pT0 bladder cancer. Patients were matched on the basis of age, gender and ASA score. The retrospective nature of this study precluded a standardized followup protocol. Rather, patient followup was directed by the treating physicians with regard to timing of repeat imaging and clinical evaluation. Typically this includes at least annual evaluation with office visit, stoma therapy consultation, complete blood count, basic metabolic panel, vitamin B12 level (if ileum is used) and upper urinary tract imaging (via computerized tomography or loopogram).
Survival was estimated as time from cystectomy to death using the Kaplan-Meier method. Comparison of preoperative and postoperative need for transfusion was performed via matched pairs analysis by t-test. All tests were 2-sided with p
Purpose: We evaluate the clinical presentation, management and outcomes of patients undergoing cystectomy for refractory hemorrhagic cystitis. Materials and Methods: We identified 21 patients with refractory hematuria treated with cystectomy at our institution between 2000 and 2012. Clot evacuation, bladder fulguration and bladder irrigation had failed in all patients before cystectomy. In addition, 45% of patients had received prior intravesical therapy (aminocaproic acid, alum or formalin), hyperbaric oxygen therapy (25%), nephrostomy tube placement for attempted urinary diversion (15%) and/or selective bladder angioembolization (5%). Results: Median patient age at surgery was 77 years (IQR 72, 80) and 81% (17 of 21) of patients were male. The most common etiology for hemorrhagic cystitis was prior radiation therapy for prostate cancer (17, 81%). Median time from receipt of radiation to cystectomy in these patients was 91 months (IQR 73, 125). Median ASAÒ (American Society of Anesthesiologists) score at cystectomy was 3 and median preoperative hemoglobin was 10.2 gm/dl. Median length of stay after cystectomy was 10 days (IQR 7, 19). Severe (Clavien grade III to V) complications were noted in 42% of patients (8 of 19) and the 90-day mortality rate in this cohort was 16% (3 of 19). With a median postoperative followup of 13 months (IQR 4, 21), the 1 and 3-year overall survival was 84% and 52%, respectively. Conclusions: Cystectomy for hemorrhagic cystitis is associated with a high risk of perioperative complications and mortality, consistent with the baseline clinical status of this patient cohort and, as such, should remain a last resort to control bleeding after failure of conservative measures.
Abbreviations and Acronyms BMI ¼ body mass index Accepted for publication June 9, 2014. Study received institutional review board approval. Nothing to disclose. * Correspondence: 200 First St. SW, Rochester, Minnesota 55905 (telephone: 507284-4015; FAX: 507-284-4951; e-mail: Boorjian. [email protected]).
Editor’s Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1896 and 1897.
Key Words: cystitis, hemorrhage, cystectomy, survival, radiotherapy
INTRACTABLE hematuria localized to the bladder, or hemorrhagic cystitis, is characterized by diffuse bleeding from the bladder mucosa. Numerous etiologies have been described as predisposing patients to hemorrhagic cystitis, although commonly the condition results from exposure to the oxazaphosphorine class of chemotherapy or pelvic radiotherapy.1 The severity of bleeding may vary from mild hematuria that resolves with conservative management such as
hydration and bladder irrigation, to transfusion dependent hemorrhage that is refractory to therapy.1 Algorithms for sequential management of such cases have been proposed,1 including escalating intervention from intravesical instillation therapies (such as alum or formalin) to hyperbaric oxygen and even bladder angioembolization. In the setting of continued bleeding, urinary diversion has been proposed, in part to eliminate the clot
0022-5347/14/1926-1687/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.06.030 Vol. 192, 1687-1692, December 2014 Printed in U.S.A.
www.jurology.com
j
1687
1688
CYSTECTOMY FOR HEMORRHAGIC CYSTITIS
lysis effect of urokinase. While supravesical diversion with nephrostomy tube placement or conduit formation may be attempted, notably after diversion that leaves the bladder in situ, complications have been reported in up to 80% of patients, with almost half requiring hospital readmission and up to 35% requiring subsequent cystectomy.2,3 Thus, when diversion is being contemplated, the role of concomitant cystectomy merits consideration. However, a paucity of data exists regarding the outcomes of cystectomy in this setting, consisting of case reports.4,5 Given the established morbidity of cystectomy,6,7 documenting perioperative outcomes in this population remains relevant to inform discussion with patients regarding anticipated risks vs benefits of surgery. Indeed, decision making is often more challenging because most patients presenting with refractory bleeding from hemorrhagic cystitis are elderly and/or infirm. Therefore, we evaluated the clinical presentation, management and outcomes in a contemporary cohort of patients with hemorrhagic cystitis who underwent cystectomy for refractory disease in the acute setting and on a planned basis.
MATERIALS AND METHODS After receiving institutional review board approval we identified 21 consecutive patients who underwent cystectomy for hemorrhagic cystitis at the Mayo Clinic from 2000 to 2012. All patients were 18 years old or older and underwent cystectomy with urinary diversion after failure of more conservative measures. Cystectomy was performed by various surgeons using standard techniques. Patient charts were reviewed, and clinicopathological variables recorded included age at cystectomy, etiology for hemorrhagic cystitis, prior therapies used (ie bladder irrigation, clot evacuation, intravesical therapy, bladder angioembolization, urinary diversion), comorbid medical conditions, ASA score, operative time, length of postoperative hospitalization, perioperative (within 90 days of surgery) complications and overall survival. Postoperative complications were graded according to the Clavien-Dindo classification.8 In the event of sequential complications, all individual complications were recorded. However, only the highest grade of complication was reported. Clinical and demographic parameters as well as overall survival were also compared to a 1:1 matched cohort of patients undergoing cystectomy for pT0 bladder cancer. Patients were matched on the basis of age, gender and ASA score. The retrospective nature of this study precluded a standardized followup protocol. Rather, patient followup was directed by the treating physicians with regard to timing of repeat imaging and clinical evaluation. Typically this includes at least annual evaluation with office visit, stoma therapy consultation, complete blood count, basic metabolic panel, vitamin B12 level (if ileum is used) and upper urinary tract imaging (via computerized tomography or loopogram).
Survival was estimated as time from cystectomy to death using the Kaplan-Meier method. Comparison of preoperative and postoperative need for transfusion was performed via matched pairs analysis by t-test. All tests were 2-sided with p
