Tumor infiltrating B-cells are increased in prostate cancer tissue.

BACKGROUND: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. METHODS: Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D'Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D'Amico risk groups and disease recurrence. RESULTS: For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D'Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. CONCLUSIONS: Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets.

PCSD1, a new patient-derived model of bone metastatic prostate cancer, is castrate-resistant in the bone-niche.

INTRODUCTION: Prostate cancer bone metastasis occurs in 50-90% of men with advanced disease for which there is no cure. Bone metastasis leads to debilitating fractures and severe bone pain. It is associated with therapy resistance and rapid decline. Androgen deprivation therapy (ADT) is standard of care for advanced prostate cancer, however, bone metastatic prostate cancer (PCa) often becomes resistant to ADT. There are few pre-clinical models to understand the interaction between the bone microenvironment and prostate cancer. Here we report the castrate resistant growth in the bone niche of PCSD1, a patient-derived intra-femoral xenograft model of prostate bone metastatic cancer treated with the anti-androgen, bicalutamide. METHODS: PCSD1 bone-niche model was derived from a human prostate cancer femoral metastasis resected during hemiarthroplasty and serially transplanted into Rag2(-/-); γ c(-/-) mice intra-femorally (IF) or sub-cutaneously (SC). At 5 weeks post-transplantation mice received bicalutamide or vehicle control for 18 days. Tumor growth of PCSD1 was measured with calipers. PSA expression in PCSD1 xenograft tumors was determined using quantitative RT-PCR and immunohistochemistry. Expression of AR and PSMA, were also determined with qPCR. RESULTS: PCSD1 xenograft tumor growth capacity was 24 fold greater in the bone (intra-femoral, IF) than in the soft tissue (sub-cutaneous, SC) microenvironment. Treatment with the anti-androgen, bicalutamide, inhibited tumor growth in the sub-cutaneous transplantation site. However, bicalutamide was ineffective in suppressing PCSD1 tumor growth in the bone-niche. Nevertheless, bicalutamide treatment of intra-femoral tumors significantly reduced PSA expression (p < = 0.008) and increased AR (p < = 0.032) relative to control. CONCLUSIONS: PCSD1 tumors were castrate resistant when growing in the bone-niche compared to soft tissue. Bicalutamide had little effect on reducing tumor burden in the bone yet still decreased tumor PSA expression and increased AR expression, thus, this model closely recapitulated castrate-resistant, human prostate cancer bone metastatic disease. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study bone metastatic disease and for pre-clinical drug development of novel therapies for inhibiting therapy resistant prostate cancer growth in the bone-niche.

Determinants of renal functional decline after open partial nephrectomy: a comparison of warm, cold, and non-ischemic modalities.

INTRODUCTION: Renal functional decline after partial nephrectomy (PN) may be related to a variety of nonmodifiable and modifiable factors, including ischemia time (IT) and modality. We sought to determine the impact of these factors on renal functional degeneration after PN. MATERIALS AND METHODS: Multicenter retrospective analysis (n = 347) was performed, identifying patients who underwent open PN using warm, cold, and non-ischemic techniques. Primary outcome was development of de novo chronic kidney disease (CKD), (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2), at 1 year follow up. Univariate and multivariable analysis (MVA) were performed examining factors associated with ischemia technique and the development of de novo CKD. RESULTS: Median follow up 34.7 months. Two hundred and forty-one patients underwent warm ischemic, 31 cold ischemic, and 75 clampless PN. Patient characteristics were similar between groups. Clampless group had lower mean RENAL scores (6.4) than cold (7.9, p = 0.005) and warm (7, p = 0.037) ischemia groups. Cold ischemia cohort had longer median IT than the warm cohort (50min versus 25 min, p = 0.001). There were no significant differences in proportion of patients developing de novo CKD (warm 14.9%, cold 15%, clampless 8.7%, p = 0.422). MVA demonstrated that neither ischemic modality nor IT ≥ 30 minutes was associated with development of de novo CKD, while RENAL scores of increasing complexity (RENAL score 7-9 OR 4.32, p = 0.003; RENAL score ≥ 10 OR 15.42, p < 0.001) were independently associated with de novo CKD. CONCLUSIONS: Increasing tumor complexity, as indicated by the RENAL score, was an overriding determinant of post PN renal functional outcome. Prospective investigation is requisite to elucidate risk and protective factors for renal functional degeneration after PN.

Urologic outcomes of pediatric pelvic neuroblastoma presenting in acute urinary retention.

PURPOSE: To evaluate long-term urologic outcomes of patients with pelvic neuroblastoma (NB) presenting with urinary retention. METHODS: Five cases of pelvic NB presenting with urinary retention were identified between 1971 and 2011. Clinical presentation, treatment, survival and long-term voiding outcomes were analyzed. RESULTS: All five patients presented with acute urinary retention and pelvic outlet dysfunction including bladder perforation (20%), constipation (40%), or fecal incontinence (20%). The presenting age ranged from 7 days to 4 years with female to male ratio of 3:2. Two patients presented with bilateral hydronephrosis and three patients were stage 4 at presentation. All required debulking surgery, four patients required combined anterior and posterior approaches for tumor resection, with two patients requiring concurrent laminectomy. Adjuvant or neoadjuvant chemoradiation was used in four of five cases. Follow-up ranged from 2 to 41 years. Although the long-term oncological outcome is favorable, urologic outcomes of these patients ranged from normal bladder function to the need significant reconstructive procedures. CONCLUSION: Urologic outcomes are related to pelvic nerve and organ preservation during resection more than the severity of urinary symptoms at presentation.

Surgical Management of Nephrolithiasis in the Bottlenose Dolphin: Collaborations Between the Urologist and Veterinarian.

Background: Cohorts of bottlenose (Tursiops truncatus) dolphins are at significant risk for nephrolithiasis development. However, effective surgical treatment has been limited due to absence of literature and also familiarity by both veterinarians and urologists. Recently a joint veterinarian and urology team were called to treat local bottlenose dolphins in San Diego, CA, and they performed several cases. The fund of knowledge from these cases is presented for future providers who may be asked to surgically treat these animals. Case Presentation: Two surgical kidney stone cases were performed by a joint veterinarian and physician team. An effective ureteroscopic stone removal was performed on a 39-year-old female bottlenose dolphin with 9.7 mm distal ureteral calculus. The second case involved laparoscopic ureterolithotomy on a 31-year-old male bottlenose dolphin with a 6-mm right distal ureteral calculus that previously failed retrograde ureteroscopic removal. The stone was not effectively removed laparoscopically as well due to failure to progress associated with operative machinery malfunction. The dolphin was ultimately euthanized. Conclusion: Despite suboptimal outcome in one case, extremely valuable lessons were learned during both cases. We present our surgical experiences, as well as pertinent anatomical differences, in these animals with the hope that this discussion will facilitate future surgical kidney stone treatment of dolphins.

Dyslipidemia is associated with an increased risk of nephrolithiasis.

The pathophysiology of nephrolithiasis is multifactorial. Obesity, diabetes mellitus and hypertension are implicated in its formation. Dyslipidemia (DLD) recently has received attention as well. Congruent with a vascular etiology in stone formation, DLD theoretically would predispose patients to nephrolithiasis. We investigated a possible association of DLD with nephrolithiasis. A random cohort of 60,000 patients was established by collecting the first 5,000 patient charts per month in the year 2000. After excluding pediatric patients, a retrospective study was performed by reviewing age, sex, comorbidities, and last patient follow-up. Median lipid laboratory levels also were reviewed. Descriptive statistics were performed as well as Cox proportional-hazards regression analysis, and univariate and multivariate analyses. 52,184 (22,717 women/29,467 men) patient charts were reviewed. The average age was 31.0 ± 15.2 years. On univariate analysis, DLD was associated with nephrolithiasis with a hazard ratio (HR) of 2.2 [Confidence Interval (CI), 1.9-2.5; p < 0.001] and on multivariate analysis HR = 1.2 (1.0-1.5; p = 0.033). Low-density lipoprotein and triglycerides had no association with stone disease. Patients with high-density lipoprotein (HDL) values <45 for men and <60 for women had an HR of 1.4 (1.1-1.7, 95% CI, p = 0.003) on univariate analysis and on multivariate analysis; HR = 1.27 (1.03-1.56; p = 0.024) for nephrolithiasis. DLD was associated with an increased risk of stone disease though the only specific lipid panel associated with lower nephrolithiasis was HDL. Clinicians should consider obtaining lipid levels with the intent that treatment could potentially not only mitigate atherosclerotic disease but also decrease nephrolithiasis risk.

Minimal incision laparoscopy assisted open pediatric pyeloplasty.

Minimal incision laparoscopy-assisted open pyeloplasty (MILAP) incorporates elements of open pyeloplasty (OP) and single incision laparoscopy to improve technical ease and cosmetic outcomes. Six MILAP procedures were performed using a single transumbilical incision through which the ureteropelvic junction (UPJ) is mobilized with standard laparoscopic instrumentation. The UPJ is brought extracorporeally through a 1-cm flank incision, and a traditional Anderson-Hynes open pyeloplasty is performed. Compared with OP, perioperative outcomes were similar. Follow-up renal scans all showed improvement of obstruction. A 1-cm flank incision is the only obvious scar.

Laparoscopic removal of spermatic cord to reduce incision size of open retroperitoneal lymph node dissection.

OBJECTIVE: To describe a laparoscopic-assisted modification to the traditional open retroperitoneal lymph node dissection (RPLND) to significantly shorten incision length and decrease morbidity of the laparotomy. METHODS: We describe 3 patients who underwent primary RPLND using the laparoscopic-assisted cord excision for stage I nonseminomatous germ cell testicular tumors. Spermatic cord excision is performed laparoscopically, and a standard nerve-sparing bilateral template RPLND is then performed through a supraumbilical incision. Operative time, intraoperative estimated blood loss, number of lymph nodes resected, complications, length of hospital stay, and follow-up were determined. RESULTS: All patients were clinical stage 1 (T1-2, Nx, M0 S0). The primary testicular tumor size was 2.2-5.5 cm with embryonal components, and all had negative results on abdominal and chest computed tomography imaging. Mean estimated blood loss was 267 mL (range, 100-500), operating room time was 293 minutes (range, 254-306), and all patients were discharged on postoperative day 5. There were no complications noted. Node counts were 22-33. The median length of follow-up was 20 months with no recurrence. CONCLUSION: Laparoscopic removal of the spermatic cord during open RPLND is a simple modification to the standard technique that reduces incision size without compromising the quality of open RPLND.

Impact of posterior rhabdosphincter reconstruction during robot-assisted radical prostatectomy: retrospective analysis of time to continence.

BACKGROUND AND PURPOSE: Posterior rhabdosphincter (PR) reconstruction during robot-assisted radical prostatectomy (RARP) was introduced in an attempt to improve postoperative continence. In the present study, we evaluate time to achieve continence in patients who are undergoing RARP with and without PR reconstruction. METHODS: A prospective RARP database was searched for most recent cases that were accomplished with PR reconstruction (group 1, n = 69) or with standard technique (group 2, n = 63). We performed the analysis applying two definitions of continence: 0 pads per day or 0-1 security pad per day. Patients were evaluated by telephone interview. Statistical analysis was carried out using the Kaplan-Meier method and log-rank test. RESULTS: With PR reconstruction, continence was improved when defined as 0-1 security pad per day (median time of 90 vs 150 days; P = 0.01). This difference did not achieve statistical significance when continence was defined as 0 pads per day (P = 0.12). CONCLUSIONS: A statistically significant improvement in continence rate and time to achieve continence is seen in patients who are undergoing PR reconstruction during RARP, with continence defined as 0-1 security/safety pad per day. A larger, prospective and randomized study is needed to better understand the impact of this technique on postoperative continence.