Konrad M. Szymanski

Fish consumption and prostate cancer risk: a review and meta-analysis

BACKGROUND Prostate cancer incidence varies 60-fold globally, which suggests the roles of lifestyle and dietary factors in its cause. To our knowledge, a comprehensive assessment of the association between fish consumption and prostate cancer incidence and mortality has not been reported. OBJECTIVE We conducted a meta-analysis of fish intake and prostate cancer by focusing on the incidence of prostate cancer and prostate cancer-specific mortality and included subgroup analyses based on race, fish type, method of fish preparation, and high-grade and high-stage cancer. DESIGN We searched MEDLINE and EMBASE databases (May 2009) for case-control and cohort studies that assessed fish intake and prostate cancer risk. Two authors independently assessed eligibility and extracted data. RESULTS There was no association between fish consumption and a significant reduction in prostate cancer incidence [12 case-control studies (n = 5777 cases and 9805 control subjects), odds ratio (OR): 0.85; 95% CI: 0.72, 1.00; and 12 cohort studies (n = 445,820), relative risk (RR): 1.01; 95% CI: 0.90, 1.14]. It was not possible to perform a meta-analysis for high-grade disease (one case-control study, OR: 1.44; 95% CI: 0.58, 3.03), locally advanced disease (one cohort study, RR: 0.80; 95% CI: 0.61, 1.13), or metastatic disease (one cohort study, RR: 0.56; 95% CI: 0.37, 0.86). There was an association between fish consumption and a significant 63% reduction in prostate cancer-specific mortality [4 cohort studies (n = 49,661), RR: 0.37; 95% CI: 0.18, 0.74]. CONCLUSION Our analyses provide no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer-specific mortality.

Solitary solid renal mass: can we predict malignancy?

Study Type – Therapy (retrospective cohort)

Mortality after Bladder Augmentation in Children with Spina Bifida

PURPOSE Renal failure has been a leading cause of death for children with spina bifida. Although improvements in management have increased survival, current data on mortality are sparse. Bladder augmentation, a modern intervention to preserve renal function, carries risks of morbidity and mortality. We determined long-term mortality and causes of death in patients with spina bifida treated with bladder augmentation. MATERIALS AND METHODS We retrospectively reviewed the records of patients with spina bifida who underwent bladder augmentation between 1979 and 2013. Those born before 1972 or older than 21 years at augmentation were excluded. Demographic and surgical data were collected. Outcomes were obtained from medical records, death records and the Social Security Death Index. Fisher exact and Wilcoxon rank-sum tests and Kaplan-Meier plots were used for analysis. RESULTS Of 888 patients in our bladder reconstruction database 369 with spina bifida met inclusion criteria. Median followup was 10.8 years. A total of 28 deaths (7.6%) occurred. The leading causes of mortality were nonurological infections (ventriculoperitoneal shunt related, decubitus ulcer fasciitis, etc) and pulmonary disease. Two patients (0.5%) died of renal failure. No patient died of malignancy or bladder perforation. Patients with a ventriculoperitoneal shunt had a higher mortality rate than those without a shunt (8.9% vs 1.5%, p = 0.04). CONCLUSIONS Previously reported mortality rates of 50% to 60% in patients with spina bifida do not appear to apply in children who have undergone bladder augmentation. On long-term followup leading causes of death in patients with spina bifida after bladder augmentation were nonurological infections rather than complications associated with augmentation or renal failure.

Long-term outcomes of catheterizable continent urinary channels: What do you use, where you put it, and does it matter?

INTRODUCTION Appendicovesicostomy (APV) and Monti ileovesicostomy (Monti) are commonly used catheterizable channels with similar outcomes on short-term follow-up. Their relative long-term results have not been previously published. OBJECTIVE Our goal was to assess long-term durability of APV and Monti channels in a large patient cohort. STUDY DESIGN In this retrospective cohort study, we retrospectively reviewed consecutive patients ≤21 years old undergoing APV and Monti surgery at our institution (1990-2013). We collected data on demographics, channel type, location, continence and stomal and subfascial revisions. Kaplan-Meier survival and Cox proportional hazards analysis were used. RESULTS Of 510 patients meeting inclusion criteria, 214 patients had an APV and 296 had a Monti (50.5% spiral Monti). Median age at surgery was 7.4 years for APV (median follow-up: 5.7 years) and 8.7 years for Monti (follow-up: 7.7 years). Stomal stenosis, overall stomal revisions and channel continence were similar for APV and Monti (p ≥ 0.26). Fourteen APVs (6.5%) had subfascial revisions compared to 49 Montis (16.6%, p = 0.001). On survival analysis, subfascial revision risk at 10 years for APV was 8.6%, Monti channels excluding spiral umbilical Monti: 15.5% and spiral umbilical Monti: 32.3% (p < 0.0001, Figure). On multivariate regression, Monti was 2.09 times more likely than APV to undergo revision (p = 0.03). The spiral Monti to the umbilicus, in particular, was 4.23 times more likely than APV to undergo revision (p < 0.001). Concomitant surgery, gender, age and surgery date were not significant predictors of subfascial revision (p ≥ 0.17). Stomal location was significant only for spiral Montis. DISCUSSION Our study has several limitations. Although controlling for surgery date was a limited way of adjusting for changing surgical techniques, residual confounding by surgical technique is unlikely, as channel implantation technique was typically unrelated to channel type. We did not include complications managed conservatively or endoscopically. In addition, while we did not capture patients who were lost to follow-up, we attempted to control for this through survival analysis. CONCLUSIONS We demonstrate, durable long-term results with the APV and Monti techniques. The risk of channel complications continues over the channels lifetime, with no difference in stomal complications between channels. At 10 years after initial surgery, Monti channels were twice as likely to undergo a subfascial revision (1 in 6) than APV (1 in 12). The risk is even higher in for the spiral umbilical Monti (1 in 3).

Cutting for Stone in Augmented Bladders—What is the Risk of Recurrence and is it Impacted by Treatment Modality?

PURPOSE Bladder stones are common after bladder augmentation, often resulting in numerous procedures for recurrence. We sought to determine whether surgical technique and stone fragmentation are significant predictors of bladder stone recurrence after bladder augmentation. MATERIALS AND METHODS We retrospectively reviewed 107 patients treated for first bladder stones at our institution. Patient demographics, details of surgeries, stone therapy and recurrence were reviewed. Kaplan-Meier survival and Cox proportional hazards analysis were used to determine predictors of time to first stone recurrence. RESULTS Of 107 patients 55.1% were female and 79.4% had neuropathic bladder. Patients underwent augmentation at a median age of 8.0 years (range 2.4 to 22.8) and were followed for a median of 12.4 years (1.8 to 34). Segments used for augmentation included ileum (72.9% of cases), sigmoid (16.8%), cecum/ileocecum (9.4%) and other (ureter, stomach/ileum, 1.8%). Bladder neck procedures were performed in 63.6% of patients and catheterizable channels in 75.7%. First stone surgery occurred at a median of 3.1 years after augmentation (range 5 months to 21.8 years). Endoscopy was used in 66.4% of cases and open cystolithotomy in 33.6%. Overall 47.7% of stones were fragmented. Bladder stones recurred in 47.7% of patients (median recurrence time 9.5 years, range 3 months to 14.7 years). Recurrence risk was greatest in the first 2 years postoperatively (12.1% per patient per year, p = 0.03). Recurrence risk did not change with technique (endoscopic vs open) or fragmentation, even after controlling for surgical and clinical variables. CONCLUSIONS Bladder stones recurred in almost half of the patients at 9 years postoperatively independent of treatment technique and patient characteristics. As a high risk group, yearly x-ray of the kidneys, ureters and bladder, and ultrasound of the kidneys and bladder are recommended in these patients.

Factors Determining Fluoroscopy Time During Ureteroscopy

PURPOSE The aim of this study was to prospectively identify predictors of radiation exposure during ureteroscopy. PATIENTS AND METHODS Eighty-five consecutive patients who presented for ureteroscopies and laser lithotripsy were considered. Fluoroscopy time (FT) was obtained from radiology reports for each patient, and clinical data were obtained from chart review. Nine patients were excluded (three unconfirmed FTs, four staghorn calculi, one ectopic kidney, and one multiple ureteral strictures). Seventy-six patients were included in the study. Univariate and multivariate linear regression were used to identify factors that determined FT. RESULTS The patient cohort was 65.8% male with a mean age of 52.7 years. Mean FT was 183 s, and mean surgical time was 68.4±29 minutes. Mean stone size was 10±5 mm in the greatest dimension. A large proportion of patients (50%) had renal stones, multiple stones were present in 31.6% of cases, and 22.3% of stones were radiolucent. Cases were equally distributed between surgeons A and B, and 46% of patients had preoperative stents. On multivariate analysis, increased FT was independently associated with surgeon A (104 additional seconds per case, P<0.001), longer duration of surgery (14 s per 10 minutes, P<0.001), and male patients (54 s per procedure, P=0.02). Age, stone characteristics, presence of ureteral stent, and stone-free status did not correlate with FT. CONCLUSIONS Surgeon behavior, longer duration of surgery, and male gender were significant predictors of FT and, hence, radiation exposure during ureteroscopy. In the present study, stone characteristics were not found to be predictors of FT.

A Novel Mechanism of PPAR Gamma Induction via EGFR Signalling Constitutes Rational for Combination Therapy in Bladder Cancer

Background Two signalling molecules that are attractive for targeted therapy are the epidermal growth factor receptor (EGFR) and the peroxisome proliferator-activated receptor gamma (PPARγ). We investigated possible crosstalk between these 2 pathways, particularly in light of the recent evidence implicating PPARγ for anticancer therapy. Principal Findings As evaluated by MTT assays, gefitinib (EGFR inhibitor) and DIM-C (PPARγ agonist) inhibited growth of 9 bladder cancer cell lines in a dose-dependent manner but with variable sensitivity. In addition, combination of gefitinib and DIM-C demonstrated maximal inhibition of cell proliferation compared to each drug alone. These findings were confirmed in vivo, where combination therapy maximally inhibited tumor growth in contrast to each treatment alone when compared to control (p<0.04). Induction of PPARγ expression along with nuclear accumulation was observed in response to increasing concentrations of gefitinib via activation of the transcription factor CCAT/enhancer-binding protein-β (CEBP-β). In these cell lines, DIM-C significantly sensitized bladder cancer cell lines that were resistant to EGFR inhibition in a schedule-specific manner. Conclusion These results suggest that PPARγ agonist DIM-C can be an excellent alternative to bladder tumors resistant to EGFR inhibition and combination efficacy might be achieved in a schedule-specific manner.

All Incontinence is Not Created Equal: Impact of Urinary and Fecal Incontinence on Quality of Life in Adults with Spina Bifida

Purpose: We previously reported that the self‐reported amount of urinary incontinence is the main predictor of lower health related quality of life in adults with spina bifida. In this study we sought to determine the impact of fecal incontinence on health related quality of life after correcting for urinary incontinence. Materials and Methods: An international sample of adults with spina bifida was surveyed online in 2013 to 2014. We evaluated fecal incontinence in the last 4 weeks using clean intervals (less than 1 day, 1 to 6 days, 1 week or longer, or no fecal incontinence), amount (a lot, medium, a little or none), number of protective undergarments worn daily and similar variables for urinary incontinence. Validated instruments were used, including QUALAS‐A (Quality of Life Assessment in Spina bifida for Adults) for spina bifida specific health related quality of life and the generic WHOQOL‐BREF (WHO Quality of Life, short form). Linear regression was used (all outcomes 0 to 100). Results: Mean age of the 518 participants was 32 years and 33.0% were male. Overall, 55.4% of participants had fecal incontinence, 76.3% had urinary incontinence and 46.9% had both types. On multivariate analysis fecal incontinence was associated with lower bowel and bladder health related quality of life across all amounts (−16.2 for a lot, −20.9 for medium and −18.5 for little vs none, p <0.0001) but clean intervals were not significant (−4.0 to −3.4, p ≥0.18). Conversely, health related quality of life was lower with increased amounts of urinary incontinence (−27.6 for a lot, −18.3 for medium and −13.4 for little vs none, p <0.0001). Dry intervals less than 4 hours were not associated with lower health related quality of life (−4.6, p = 0.053) but the use of undergarments was associated with it (−7.5 to −7.4, p ≤0.01). Fecal incontinence and urinary incontinence were associated with lower WHOQOL‐BREF scores. Conclusions: Fecal incontinence and urinary incontinence are independent predictors of lower health related quality of life in adults with spina bifida. Health related quality of life is lower with an increasing amount of urinary incontinence. Fecal incontinence has a more uniform impact on health related quality of life regardless of frequency or amount.

A comparison of the Monti and spiral Monti procedures: A long-term analysis

INTRODUCTION/BACKGROUND The Monti ileovesicostomy provides an excellent substitution for an appendicovesicostomy when the appendix is unavailable or suitable for use. The spiral Monti is a useful modification to the traditional Monti as it allows creation of a longer channel when needed. In 2007, the short-term outcomes were reported; they compared traditional and spiral Monti in 188 patients with an average follow-up of 43 months. In the present population, a total of 25 subfasical revisions were performed in 21 patients: nine (8.3%) subfascial revisions in the traditional Monti (TM) patients and 12 (15.2%) subfascial revisions in the spiral Monti (SM) patients. The study found an increased risk of subfascial revisions of either TM or SM when the stoma was located at the umbilicus versus right lower quadrant (16.8% vs 6.3%, P < 0.05). On subgroup analysis, this increased subfascial revision rate appeared to be driven by SM channels to the umbilicus rather than other stomal locations, but this trend was not statistically significant. OBJECTIVE It was hypothesized that with longer follow-up, the spiral Monti would require more subfascial revisions due to progressive lengthening of the channel. STUDY DESIGN A retrospective chart review was performed for all patients undergoing a traditional Monti (TM) or spiral Monti (SM) procedure at the present institution (1997-2013). Patient demographics, bowel segment used, stomal location, channel or stomal revisions, number of anesthetic endoscopic procedures performed, and indications for revision were reviewed. Kaplan-Meier analysis and Cox proportional hazards modeling was used for analysis. RESULTS Of the 296 patients identified, 146 had Monti procedures and 150 had spiral Monti procedures (median follow-up 7.7 years). Median age at surgery was 10.6 years. Myelomeningocele was the most common underlying cause of neuropathic bladder, totaling 169 (57.1%) patients. Stomas were located at the umbilicus (106, 35.8%), right lower quadrant (183, 61.8%) and left lower quadrant (seven, 2.4%). Median follow-up for the entire cohort was 7.7 years (range: 1 month-15.7 years). Stomal stenosis rate was 7.4%, and 96.6% of the channels were continent. A total of 87 revisions were performed in 74 patients (25.0%). Of these, 55 were subfascial revisions in 49 patients (16.6%). The umbilical spiral Monti on univariate and multivariate analysis was found to be over twice as likely to undergo subfascial revision. DISCUSSION The majority of patients with a Monti channel had durable results and did not require further channel surgery with long-term follow-up. Spiral Monti channels to the umbilicus were more than twice as likely to undergo subfascial revision compared to all other Monti channels. Overall, one in three umbilical SM channels required a subfascial revision at 10 years after the initial surgery, compared to one in six of all other Monti channels. The study was limited by being a retrospective, single-center series; however, it does represent the largest series of pure SM and TM patients. It focused only on surgical interventions, thus was likely to underestimate the overall risk of complications, as some complications were managed conservatively. As in all studies, some patients were lost to follow-up and inevitably some of these may have had complications. Correction for this was attempted through survival analysis. CONCLUSION The present study reported durable and reliable long-term results with Monti and spiral Monti procedures based on a large patient cohort. Spiral Monti to the umbilicus was more than twice as likely to require a subfascial revision.

Ultrasound diagnosis of multicystic dysplastic kidney: Is a confirmatory nuclear medicine scan necessary?

OBJECTIVE It is critical to differentiate between a multicystic dysplastic kidney (MCDK) and a kidney with severe hydronephrosis as the treatment varies significantly. We designed a study to compare renal ultrasound (RUS) to nuclear medicine (NM) scan in the diagnosis of MCDK, in order to determine if RUS can be used for the definitive diagnosis of MCKD without use of NM scan. MATERIALS AND METHODS We performed a retrospective review of children with MCDK, who underwent both a RUS and Tc-99m MAG3 or DMSA scan. We planned to calculate the positive predictive value of an RUS diagnosis of MCDK, using NM scan diagnosis of a nonfunctioning kidney as the gold standard. RESULTS The diagnosis of MCDK was made by RUS in 91 patients, 84 of whom had a normal bladder US. NM confirmed the diagnosis of MCDK in all 84 of these patients (100%). CONCLUSION We have demonstrated a high predictive value for RUS in the diagnosis of MCDK. Our data support that in healthy infants with RUS diagnosis of unilateral MCDK and normal bladder US, NM scan may be unnecessary to confirm the diagnosis.