Brian J. Linder

The Impact of Perioperative Blood Transfusion on Cancer Recurrence and Survival Following Radical Cystectomy

BACKGROUND While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. OBJECTIVE To evaluate the association of PBT with disease recurrence and mortality following RC. DESIGN, SETTING, AND PARTICIPANTS We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. RESULTS AND LIMITATIONS A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2-4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p<0.0001), had a worse Eastern Cooperative Oncology Group performance status (p<0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9-15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p<0.001), and overall survival (45% vs 63%; p<0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p<0.0001) and all-cause mortality (HR: 1.05; p<0.0001). Limitations include selection bias and lack of standardized transfusion criteria. CONCLUSIONS We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.

Long-term Outcomes Following Artificial Urinary Sphincter Placement: An Analysis of 1082 Cases at Mayo Clinic

OBJECTIVE To evaluate long-term device outcomes following primary artificial urinary sphincter (AUS) implantation. MATERIALS AND METHODS We identified 1802 male patients with stress urinary incontinence that underwent AUS placement from 1983 to 2011. Of these, 1082 (60%) were involving primary implantations and comprise the study cohort. Multiple clinical and surgical variables were evaluated for potential association with treatment failure, defined as any secondary surgery. Patient follow-up was obtained through office examination, operative report, and written or telephone correspondence. RESULTS Patients undergoing AUS implantation had a median age of 71 years (interquartile range 66-76) and median follow-up of 4.1 years (interquartile range 0.8-7.7). Overall, 338 of 1082 patients (31.2%) underwent secondary surgery, including 89 for device infection and/or erosion, 131 for device malfunction, 89 for urethral atrophy, and 29 for pump malposition or tubing complications. No patient-related risk factors were independently associated with an increased risk of secondary surgery on multivariable analysis. Secondary surgery-free survival was 90% at 1 year, 74% at 5 years, 57% at 10 years, and 41% at 15 years. CONCLUSION Primary AUS implantation is associated with acceptable long-term outcomes. Recognition of long-term success is important for preoperative patient counseling.

Long-Term Device Outcomes of Artificial Urinary Sphincter Reimplantation Following Prior Explantation for Erosion or Infection

PURPOSE We evaluated clinical outcomes in patients treated with artificial urinary sphincter reimplantation after artificial urinary sphincter explantation for erosion or infection. MATERIALS AND METHODS We identified 704 consecutive artificial urinary sphincter implantation procedures performed at our institution from 1998 to 2012, including 497 (71%) as primary implantation and 138 (20%) as revision surgery for device malfunction. A total of 69 patients (10%) had undergone at least 1 prior artificial urinary sphincter explantation secondary to urethral erosion and/or device infection, of whom 36 (52%) were treated with 2 to 5 prior reimplantation procedures. Patient followup was performed through office examination, or written or telephone correspondence. RESULTS Patients treated with artificial urinary sphincter reimplantation had a median age of 78 years (IQR 72, 80) and a median followup of 34 months (IQR 5, 61). Artificial urinary sphincter reimplantation was done a median of 9 months (IQR 6, 13) after explantation. Patients treated with reimplantation after erosion or infection were more likely to require repeat explantation than those with primary implantation (13 of 69 or 19% vs 32 of 497 or 6.4%, p = 0.002). However, when evaluating repeat procedures, the 5-year device survival rate after reimplantation due to erosion or infection vs primary implantation was 68% vs 76% (p = 0.38). CONCLUSIONS Our findings suggest that artificial urinary sphincter reimplantation after explantation for urethral erosion and/or device infection is associated with an increased rate of recurrent erosion/infection requiring repeat explantation. However, in appropriately selected and counseled patients clinically acceptable long-term device use can be achieved.

Outcomes following radical cystectomy for nested variant of urothelial carcinoma: a matched cohort analysis.

PURPOSE We evaluated oncological outcomes after radical cystectomy in patients with the nested variant of urothelial carcinoma and compared survival to that in patients with pure urothelial carcinoma of the bladder. MATERIALS AND METHODS We identified 52 patients with the nested variant who were treated with radical cystectomy between 1980 and 2004. Pathological specimens were re-reviewed by a single genitourinary pathologist. Patients were matched 1:2 by age, gender, ECOG (Eastern Cooperative Oncology Group) performance status, pathological tumor stage and nodal status to patients with pure urothelial carcinoma. Survival was estimated using the Kaplan-Meier method and compared with the log rank test. RESULTS Patients with the nested variant had a median age of 69.5 years (IQR 62, 74) and a median postoperative followup of 10.8 years (IQR 9.3, 11.2). Nested variant cancer was associated with a high rate of adverse pathological features since 36 patients (69%) had pT3-T4 disease and 10 (19%) had nodal invasion. Eight patients (15%) with nested variant cancer received perioperative chemotherapy. When patients with the nested variant were matched to a cohort with pure urothelial carcinoma, no significant differences were noted in 10-year local recurrence-free survival (83% vs 80%, p = 0.46) or 10-year cancer specific survival (41% vs 46%, p = 0.75). CONCLUSIONS The nested variant of urothelial carcinoma is associated with a high rate of locally advanced disease at radical cystectomy. However, when stage matched to patients with pure urothelial carcinoma, patients with the nested variant did not have an increased rate of recurrence or adverse survival. Further studies are required to validate these findings and guide the optimal multimodal treatment approach to these patients.

Perioperative Blood Transfusion and Radical Cystectomy: Does Timing of Transfusion Affect Bladder Cancer Mortality?

BACKGROUND While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established. OBJECTIVE The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes. RESULTS AND LIMITATIONS In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT (p=0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p=0.02), while receipt of postoperative BT was not (p=0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0-15.7). Five-year RFS (p<0.001) and CSS (p<0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p=0.001), cancer-specific mortality (HR: 1.55; p=0.0001), and all-cause mortality (HR: 1.40; p<0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death. CONCLUSIONS Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality. PATIENT SUMMARY In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality.

Long-term outcomes of penile prostheses for the treatment of erectile dysfunction

Since their introduction 60 years ago, penile prostheses have remained the standard therapy for the management of refractory erectile dysfunction, with multiple long-term series reporting outcomes. A PubMed search was performed from 1990 to present, and outcomes of penile prosthetics were reviewed. Studies with <12 months follow-up were excluded. Overall mechanical survival of three-piece prostheses range from 81–94, 68–89 and 57–76% at 5, 10 and 15 years, respectively. Contemporary infection rates following recent device modifications are 1–2% (low risk) to 2–3% (high risk). Patient satisfaction ranges from 75–100% and varies by prosthetic device. Outcomes are further reviewed among specialized populations (revision surgery, Peyronie’s disease, priapism, corporal fibrosis and neurologic impairments). Penile prostheses remain a viable surgical treatment option with excellent mechanical reliability, low infection rates and significant patient/partner satisfaction.

Perioperative Complications following Artificial Urinary Sphincter Placement.

PURPOSE We evaluated perioperative complications in patients undergoing primary artificial urinary sphincter placement and the potential impact of these complications on device outcomes. MATERIALS AND METHODS During the 2-year period from 2012 to 2014 we retrospectively evaluated the outcomes of 197 consecutive artificial urinary sphincter implantation procedures performed at our institution for post-prostatectomy incontinence. Of these cases 100 that were primary implantations comprise the study cohort. Perioperative complications, defined as those occurring within 6 weeks postoperatively, were classified by the Clavien-Dindo classification. After office evaluation at 6 weeks patients were followed for symptoms. Patient followup was obtained through office examination and telephone correspondence. RESULTS Patients undergoing primary artificial urinary sphincter implantation had a median age of 71.5 years (IQR 66, 76). The overall rate of any complication (Clavien I-V) within 6 weeks of surgery was 35%, including urinary retention in 31% of cases, cellulitis in 1%, device infection in 2% and urethral erosion in 2%. No significant differences in pertinent clinical comorbidities such as age (p = 0.69), hypertension (p = 0.95), coronary artery disease (p = 0.57), diabetes mellitus (p = 0.17), body mass index (p = 0.47), prior pelvic radiation therapy (p = 0.45), prior urethral sling placement (p = 0.91) or transcorporeal urethral cuff placement (p = 0.22) were found between patients with and without complications. Median followup was similar between those with and without postoperative urinary retention (p = 0.14). Postoperative urinary retention was associated with adverse 6-month device survival (76% vs 89%, p = 0.04). CONCLUSIONS The most common complication of artificial urinary sphincter placement is urinary retention. Serious adverse events following artificial urinary sphincter placement are rare. Postoperative urinary retention is associated with adverse short-term device survival rates.

Cystectomy for Refractory Hemorrhagic Cystitis: Contemporary Etiology, Presentation and Outcomes

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 ASA® (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.

The impact of perioperative blood transfusion on survival after nephrectomy for non-metastatic renal cell carcinoma (RCC)

To evaluate the association of perioperative blood transfusion (PBT) with survival after nephrectomy.

The Impact of Histological Reclassification during Pathology Re-Review—Evidence of a Will Rogers Effect in Bladder Cancer?

PURPOSE We investigated the association of histological reclassification during pathology re-review of radical cystectomy specimens with clinicopathological outcomes in patients initially classified with urothelial carcinoma. MATERIALS AND METHODS We identified 1,211 patients initially diagnosed with urothelial carcinoma at radical cystectomy between 1980 and 2005. All pathological specimens were re-reviewed by a urological pathologist. Survival was estimated using the Kaplan-Meier method and compared with the log rank test. RESULTS Of 1,211 cases previously recorded as pure urothelial carcinoma 406 (33%) were reclassified as variant histology. The most common variant histologies identified were squamous in 151 patients (37%) and micropapillary in 62 (15%). Variant histology on re-review was associated with a higher rate of extravesical disease (71%) than urothelial carcinoma at initial diagnosis (52%) or pure urothelial carcinoma on re-review (42%, p<0.0001). Median postoperative followup was 11.1 years, during which 976 patients died, including 564 of bladder cancer. Notably, reclassification resulted in significant stratification of 10-year cancer specific survival, which was 50% in patients with pure urothelial carcinoma after re-review, 47% in those with urothelial carcinoma on initial interpretation and 42% in those with variant histology on re-review (p=0.03). Ten-year overall survival in patients with urothelial carcinoma on re-review, urothelial carcinoma at initial interpretation and variant histology on re-review was 29%, 27% and 24%, respectively (p=0.04). CONCLUSIONS Pathological re-review of radical cystectomy specimens identified variant histology in a third of patients. These variants are associated with a high rate of locally advanced disease, which may impact the noted rates of cancer specific and overall survival. Thus, it is critical to be aware of re-review status when interpreting outcomes from historical data sets and stratifying risk.