Two recent studies have shown that modern bariatric surgery leads to significant hyperoxaluria and risk of nephrolithiasis. However, neither report evaluates the use or effects of stone risk modifying agents in these patients. We sought to determine the impact of medical management on stone risk profile in patients who have undergone Roux-en-y gastric bypass. Twenty-four-hour urine collections of all patients referred to a tertiary clinic for nephrolithiasis in the past 4 years were reviewed. Those patients with severe (>75 mg/day) hyperoxaluria were identified. Retrospective chart review was performed to identify those patients with a history of bariatric surgery. Student’s t-test was used to compare mean urinary parameters between bariatric and non-bariatric patients. Out of all stone formers within our 24-h urine collection database, 39 patients had severe hyperoxaluria (oxalate >75 mg/day). Twenty-six patients had complete information for review. Five patients had a history of bariatric surgery. Compared with non-bariatric patients, those with a history of bariatric surgery had increased use of oral calcium (80 vs. 28%) and citrate supplementation (100 vs. 47%), higher urinary oxalate (129 vs. 91 mg/day) and volume (2.9 vs. 2.4 L/day), lower urinary citrate (390 vs. 800 mg/day) and calcium (155 vs. 235 mg/day), and a decreased supersaturation of calcium oxalate (6.7 vs. 11). Appropriate medical management, in particular oral calcium and citrate supplementation, and perhaps most importantly aggressive fluid intake can mitigate some of the effects of enteric hyperoxaluria caused by fat malabsorption after modern bariatric surgery.

Introduction

Two recent studies have shown that modern bariatric surgery leads to significant hyperoxaluria and risk of nephrolithiasis. However, neither report evaluates the use or effects of stone risk modifying agents in these patients. We sought to determine the impact of medical management on stone risk profile in patients who have undergone Roux-en-y gastric bypass.

Materials and methods

Twenty-four-hour urine collections of all patients referred to a tertiary clinic for nephrolithiasis in the past 4 years were reviewed. Those patients with severe (>75 mg/day) hyperoxaluria were identified. Retrospective chart review was performed to identify those patients with a history of bariatric surgery. Student's t-test was used to compare mean urinary parameters between bariatric and non-bariatric patients.

Results

Out of all stone formers within our 24-h urine collection database, 39 patients had severe hyperoxaluria (oxalate >75 mg/day). Twenty-six patients had complete information for review. Five patients had a history of bariatric surgery. Compared with non-bariatric patients, those with a history of bariatric surgery had increased use of oral calcium (80 vs. 28%) and citrate supplementation (100 vs. 47%), higher urinary oxalate (129 vs. 91 mg/day) and volume (2.9 vs. 2.4 L/day), lower urinary citrate (390 vs. 800 mg/day) and calcium (155 vs. 235 mg/day), and a decreased supersaturation of calcium oxalate (6.7 vs. 11).

Conclusions

Appropriate medical management, in particular oral calcium and citrate supplementation, and perhaps most importantly aggressive fluid intake can mitigate some of the effects of enteric hyperoxaluria caused by fat malabsorption after modern bariatric surgery.

Objectives

Urinary excretion of citrate is dependent on glomerular filtration, tubular reabsorption, and excretion. Acid base status is thought to play a significant role in urinary citrate excretion. It has been assumed that increased urinary citrate will increase urinary pH. The aim of this study was to confirm the association of increased urinary citrate levels with increased urinary pH.

Methods

The 24-hour urine collections of all patients with stones referred to our clinic in the past 4 years were reviewed. The samples were collected and analyzed for routine stone risk profiles by a commercial laboratory (Litholink, Chicago, Ill). The Student t test and analysis of variance were used to compare the mean values as applicable. Pearson's correlations were also calculated for each variable.

Results

A total of 572 patients had at least one 24-hour urine sample from the past 4 years. The mean urinary citrate was 305 mg/day. The mean urinary pH of all patients was 6.14. Statistical evaluation of all patients showed no correlation between urinary citrate and pH (r = -0.04, P = 0.36). In a subset of patients with urinary potassium greater than 100 mEq/day (n = 100), urinary citrate and urinary pH were both increased; however, there was still no correlation between the two (r = 0.011, P = 0.806).

Conclusions

Despite the current dogma that increasing urinary citrate increases urinary pH, in a cohort of patients with urinary stone formation who provided 24-hour urine specimens, no correlation was found between urinary citrate and urinary pH levels.

Purpose

NCCN Guidelines® recommend annual prostate biopsies for men with low risk prostate cancer on active surveillance. We determined whether erectile function decreases with the number of biopsies experienced.

Materials and methods

During a median 3.2-year followup after prostate cancer diagnosis in 2003 to 2010 at our institution 427 men on active surveillance underwent a total of 1,197 biopsies and provided 1,398 erectile function evaluations via the Sexual Health Inventory for Men questionnaire. For analysis we decomposed the 25-point questionnaire responses into a 5-point erectile function score and a 3-level sexual activity status. We used separate models adjusted for patient characteristics to determine whether either outcome varied with biopsy exposure.

Results

At diagnosis the median age was 61 years and median prostate specific antigen was 5.3 ng/ml. Of the cases 70% were clinical stage cT1 and 93% were Gleason score less than 7. Of biopsies followed by evaluations 40% were the first undergone by the patient and 9% were the fifth to ninth. At the first erectile function evaluation 15% of men were inactive, 8% engage in stimulation and 77% engaged in intercourse. Sexual activity level changed in greater than 20% of respondents between evaluations. Adjusted erectile function scores were not associated with biopsy exposure cross-sectionally or longitudinally but they corresponded with the 50th, 63rd and 80th percentiles of erectile function by increasing sexual activity level. Similarly, sexual activity was not associated with biopsy exposure. Separated outcomes were more accurate and informative than Sexual Health Inventory for Men scores.

Conclusions

Our study had high power to detect erectile function-biopsy associations but it estimated that the effects were negligible. We recommend erectile function scores over Sexual Health Inventory for Men scores to avoid biased assessment of erectile function.

Objectives

Currently, there are few options other than cystectomy for the management of BCG refractory non-muscle invasive bladder cancer. We report our experience with intravesical combination chemotherapy using gemcitabine and MMC in such patients.

Materials and methods

We identified all patients with non-muscle invasive bladder cancer who were BCG refractory or intolerant and had been treated with intravesical gemcitabine and MMC at our institution. Patients were treated with a combination of intravesical gemcitabine (1000 mg in 50 ml sterile water) followed sequentially by intravesical MMC (40 mg in 20 ml sterile water) every week for 6 weeks (induction). Induction therapy was followed by a maintenance regimen using the same dose of gemcitabine and MMC once a month for 12 months. Data regarding patient demographics and disease information such as previous intravesical therapy, previous cystoscopy, cytology results, time to recurrence, and side effect profile were collected.

Results

A total of 10 patients (6 male and 4 female) aged 48 to 85 years (median 67 years) underwent treatment with a median follow-up of 26.5 months (4-34 months). Six patients were recurrence free and have maintained their response at a median of 14 months (4-34 months). Four patients had biopsy proven recurrence. Median time to recurrence was 6 months (range 4-13 months). The therapy was well tolerated in all patients. There were no major complications. Two patients experienced irritative lower urinary tract symptoms, which did not require cessation of therapy and one experienced a maculopapillary rash that improved with benadryl.

Conclusions

In patients with recurrent BCG refractory bladder cancer, intravesical combination chemotherapy with gemcitabine and MMC appears to be well tolerated and yields a response in a good proportion number of patients.

Objective

To determine the factors associated with downgrading between biopsy and prostatectomy in the contemporary era using extended-template biopsy techniques.

Materials and methods

The UCSF Urologic Oncology Database was used to identify subjects diagnosed with high grade prostate cancer (primary pattern 4 or 5) in at least one core on extended-pattern biopsy. Multivariable logistic regression analysis was performed to identify independent factors associated with downgrading at radical prostatectomy, defined as a change from primary pattern 4 or 5 to primary pattern 3.

Results

Downgrading occurred in 68 (34%) of 202 subjects who met the study criteria. Fourteen (47%) of 30 subjects with ≤25% of cores that were high grade and 9 (43%) of 21 subjects with <10% of total tissue containing cancer were downgraded. In a multivariable model, patients with mixed grade cores had much higher odds of downgrading than those with all high grade cores (OR 3.0 95% 1.3-7.1), P < 0.01). The proportion (per 10% increment) of positive cores containing high grade cancer (OR 0.8 95% CI 0.7-0.9 P < 0.01) and the percent (per 10% increment) of total tissue containing cancer (OR 0.7 95% CI 0.6-0.9 P = 0.01) were significantly associated with lower odds of downgrading.

Conclusions

Downgrading following radical prostatectomy is a common event. Biopsy over-grading may preclude men from active surveillance or lead to unnecessary lymphadenectomy, excess radiation, or prolonged hormone therapy. The proportion of positive biopsy cores that are high grade and the percent of total tissue containing cancer should be incorporated into decision making.

Objective

To investigate variation in the International Prostate Symptom Score (IPSS) in men following prostate brachytherapy.

Methods

From January 2004 to November 2009, 524 consecutive patients underwent prostate brachytherapy either alone or in combination with external beam radiation therapy for T1c-T3b prostate cancer. The IPSS was assessed preimplant and at 1, 6, 12, 24, 36, and 48 months after treatment. Clinical and treatment-related factors were assessed for correlations with the IPSS increase.

Results

The mean preimplant IPSS was 7.4, with the greatest mean score of 16.0 at 1 month. At 6 months, the mean total IPSS had decreased to 11.5, but it was still statistically significantly greater than that at baseline (<0.001). At 12 months, the IPSS was decreased to 8.6, slightly greater than baseline (p = 0.001). The IPSS of 45.4 % (69/152) patients gradually returned to preimplant levels and that of 71.1 % (108/152) patients returned to within 3 points of the baseline at 24 months. At 24, 36, and 48 months after seed implantation, the IPSS was 8.6, 7.7, and 8.2, respectively, and none of these values differed statistically significantly from baseline (p > 0.05). Sixteen patients (3.1 %) showed AUR, and 11 patients required catheterization. On univariate and multivariate analyses, the IPSS increase was best predicted by lower preimplant IPSS.

Conclusion

In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 24 months. The IPSS increase was best predicted by lower preimplant IPSS.

Purpose

Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time.

Patients and methods

Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates.

Results

Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy.

Conclusion

A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.

Purpose

We assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance.

Materials and methods

A cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis.

Results

A total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46).

Conclusions

There is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance.