Lance A. Mynderse

Hexaminolevulinate Guided Fluorescence Cystoscopy Reduces Recurrence in Patients With Nonmuscle Invasive Bladder Cancer

PURPOSE We assessed the impact that improved detection of nonmuscle invasive bladder cancer with hexaminolevulinate fluorescence cystoscopy may have on early recurrence rates. MATERIALS AND METHODS This prospective, randomized study enrolled 814 patients suspected of having bladder cancer at increased risk for recurrence. All patients underwent white light cystoscopy and mapping of lesions, followed by transurethral resection of the bladder when indicated. Patients in the fluorescence group also received intravesical hexaminolevulinate solution at least 1 hour before cystoscopy to induce fluorescence of cancerous lesions, and underwent additional inspection with blue light before and after transurethral resection of the bladder. Adjuvant intravesical therapy was based on risk. Followup cystoscopy at 3, 6 and 9 months was conducted with white light. RESULTS Detection was performed as a within patient comparison in the fluorescence group. In this group 286 patients had at least 1 Ta or T1 tumor (intent to treat). In 47 patients (16%) at least 1 of the tumors was seen only with fluorescence (p = 0.001). During the 9-month followup (intent to treat) there was tumor recurrence in 128 of 271 patients (47%) in the fluorescence group and 157 of 280 (56%) in the white light group (p = 0.026). The relative reduction in recurrence rate was 16%. CONCLUSIONS Hexaminolevulinate fluorescence cystoscopy significantly improves the detection of Ta and T1 lesions and significantly reduces the rate of tumor recurrence at 9 months.

Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy.

PURPOSE We assessed the impact of hexaminolevulinate fluorescence cystoscopic detection of papillary, nonmuscle invasive bladder cancer on the long-term recurrence rate. MATERIALS AND METHODS Long-term followup was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after initial resection or until recurrence. A study extension protocol was done for long-term followup of these patients. RESULTS Followup information was obtained for 261 of the 280 patients (93%) in the white light group and 255 of the 271 (94%) in the fluorescence group. Median followup in the white light and fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months in the white light group and 16.4 months in the fluorescence group (p = 0.04). The intravesical therapy rate was similar in the 2 groups (46% and 45%, respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16). CONCLUSIONS Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer time to recurrence with a trend toward improved bladder preservation.

Transdermal clonidine for ameliorating post-orchiectomy hot flashes

To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.

Juxtaglomerular cell tumor: A clinicopathologic study of four cases and review of the literature

We studied 4 new cases of juxtaglomerular cell tumor and compared their morphologic and immunohistochemicalfeatures with 2 renal hemangiopericytomas and 5 cutaneous glomus tumors. The juxtaglomerular tumors were resectedfrom 2 males and 2 females (mean age at diagnosis, 23 years). Three patients manifested with severe hypertension. Tumors ranged from 2.2 to 8.0 cm and were well circumscribed. The tumors consisted of solid sheets and nodules of variably sized tumor cells with round, oval, and spindled nuclei alternating with edematous microcystic foci. Nuclear atypia, present in all tumors, was a prominent feature in 2. Mitotic activity was not identified. All cases showed hemorrhage, numerous mast cells, and thick-walled blood vessels. Unusual features included coagulative tumor necrosis, a hemangiopericytoma-like vascular pattern, and hyalinized stroma. All tumors were immunoreactive for CD34 and actin. Ultrastructural analysis revealed the presence of rhomboid-shaped renin protogranules. Patients were treated by partial or radical nephrectomy and followed up for 14 to 48 months. There were no recurrences or metastases. The characteristic clinical and morphologic features of juxtaglomerular cell tumor permit distinction from renal hemangiopericytoma and other renal tumors.

Salvage Lymph Node Dissection for Prostate Cancer Nodal Recurrence Detected by 11C-Choline Positron Emission Tomography/Computerized Tomography

PURPOSE We report salvage lymph node dissections for prostate cancer nodal recurrence detected by (11)C-choline positron emission tomography/computerized tomography in the setting of increasing prostate specific antigen after radical prostatectomy. MATERIALS AND METHODS Retrospective chart review was performed for all patients who underwent salvage lymph node dissection for prostate cancer nodal recurrence. Only patients previously treated with radical prostatectomy were included in the study and those with evidence of local recurrence were excluded from analysis. Primary end points included biochemical recurrence, systemic progression and cancer specific mortality. RESULTS From 2009 to 2013, 52 men underwent salvage lymph node dissection. Before salvage lymph node dissection 78.8% (41 of 52) had some form of therapy after radical prostatectomy. Median age at salvage lymph node dissection was 60 years and median prostate specific antigen was 2.2 ng/ml (IQR 1.4-3.7). The median number of lymph nodes dissected was 21.5 (IQR 16-30) and the median number of positive nodes was 3.5 (IQR 1.2-6.5). Since salvage lymph node dissection 46.2% of the men (24 of 52) have had no further treatment, 34.6% (18 of 52) are on hormonal therapy and 19.2% (10 of 52) have received multiple different treatments. At the last followup at a median of 20 months (IQR 8-33), 57.7% (30 of 52) had prostate specific antigen remain less than 0.2 ng/ml, 75% (39 of 52) remained free of systemic progression and 96.2% of the men (50 of 52) were alive. Two patients died of prostate cancer. Three-year biochemical recurrence-free, systemic progression-free and cancer specific survival was 45.5%, 46.9% and 92.5%, respectively. CONCLUSIONS This represents the largest U.S. series of salvage lymph node dissection in the setting of lymph node metastatic prostate cancer after radical prostatectomy. Although followup was short and the study lacked a randomized control group, salvage lymph node dissection may represent a valid treatment option.

Effects of 100 and 300 Units of Onabotulinum Toxin A on Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A Phase II Randomized Clinical Trial

PURPOSE We conducted a 2-stage, multicenter, double-blind, randomized phase II clinical trial of 100 and 300 unit doses of onabotulinum toxin A to treat the lower urinary tract symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS Men 50 years old or older with clinically diagnosed benign prostatic hyperplasia, American Urological Association symptom index 8 or greater, maximum urinary flow rate less than 15 ml per second, voided volume 125 ml or greater, and post-void residual 350 ml or less were randomized to prostatic transrectal injection of 100 or 300 units of onabotulinum toxin A. The primary outcome was at least 30% improvement from baseline to 3 months in American Urological Association symptom index and/or maximum urinary flow rate and safety. The men were followed for 12 months. RESULTS A total of 134 men were randomized and treated (68 with 100 units, 66 with 300 units), with 131 assessed at 3 months and 108 assessed at 12 months. Each dose met the 3-month primary outcome criteria. In the 100 unit arm the mean baseline American Urological Association symptom index of 18.8 decreased by 7.1 and 6.9 at 3 and 12 months, respectively. In the 300 unit arm the baseline of 19.5 decreased by 8.9 and 7.1, respectively. In the 100 unit arm the mean baseline maximum urinary flow rate of 10.0 ml per second increased by 2.5 and 2.2, respectively, and in the 300 unit arm the baseline of 9.6 increased by 2.6 and 2.3, respectively. CONCLUSIONS The intraprostatic injection of 100 or 300 units of onabotulinum toxin A passed predetermined criteria for treatment efficacy and safety, and a randomized trial with either dose is warranted. The 100 unit dose may be preferable due to similar efficacy with reduced costs and adverse effects.

Prostate Cancer Ki-67 (MIB-1) Expression, Perineural Invasion, and Gleason Score as Biopsy-Based Predictors of Prostate Cancer Mortality: The Mayo Model

OBJECTIVE To determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality. PATIENTS AND METHODS Between 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index. RESULTS With a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms. CONCLUSION This study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PURPOSE Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. MATERIALS AND METHODS Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. RESULTS Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). CONCLUSIONS In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.

Prostate Cryotherapy Monitoring Using Vibroacoustography: Preliminary Results of an Ex Vivo Study and Technical Feasibility

The objective of this research is to prospectively evaluate the feasibility of vibroacoustography (VA) imaging in monitoring prostate cryotherapy in an ex vivo model. Baseline scanning of an excised human prostate is accomplished by a VA system apparatus in a tank of degassed water. Alcohol and dry ice mixture are used to freeze two prostate tissue samples. The frozen prostates are subsequently placed within the water tank at 27degC and rescanned. VA images were acquired at prescribed time intervals to characterize the acoustic properties of the partially frozen tissue. The frozen prostate tissue appears in the images as hypoemitting signal. Once the tissue thaws, previously frozen regions show coarser texture than prior to freezing. The margin of the frozen tissue is delineated with a well-defined rim. The thawed cryolesions show a different contrast compared with normal unfrozen prostate. In conclusion, this pilot study shows that VA produces clear images of a frozen prostate at different temperature stages. The frozen tissue appears as a uniform region with well-defined borders that are readily identified. These characteristic images should allow safer and more efficient application of prostatic cryosurgery. These results provide substantial motivation to further investigate VA as a potential modality to monitor prostate cryotherapy intraoperatively.

3.0T MR-guided laser ablation of a prostate cancer recurrence in the postsurgical prostate bed.

Biochemical recurrence of prostate cancer after definitive therapy with radical prostatectomy occurs in 25%-30% of cases. The first known case of magnetic resonance (MR) imaging-guided ablation using laser interstitial thermal therapy (LITT) for locally recurrent prostate cancer after radical prostatectomy is presented. Using 3.0T MR guidance, two laser applicators were placed via a transperineal approach. Laser ablation was performed using MR thermometry to determine the ablation endpoint and lesion coverage. Dynamic contrast-enhanced MR imaging after the procedure showed no definitive abnormal enhancement. The patient had no change in continence or potency after the procedure.