Comparison of retroperitoneal and transperitoneal robotic partial nephrectomy for Pentafecta perioperative and renal functional outcomes.

BACKGROUND: We compared quality outcomes between transperitoneal (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN). METHODS: Two-center retrospective analysis of TRPN and RRPN from 10/2009 to 10/2015. Perioperative/renal function outcomes were analyzed. Primary endpoint was Pentafecta, a composite measure of quality [negative margin, no 30-day complication, ischemia time ≤25 min, return of glomerular filtration rate (eGFR) to >90% from baseline at last follow-up, and no chronic kidney disease upstaging]. Multivariable analysis (MVA) for factors associated with lack of optimal outcome was performed. RESULTS: 404 patients (TRPN 263, RRPN 141) were analyzed. Comparing TRPN vs. RRPN, mean tumor size (3.1 vs. 2.9 cm, p = 0.122) and RENAL score (7.4 vs. 7.2, p = 0.503) were similar. Most TRPN were anterior (65.0%) and most RRPN posterior (65.3%, p < 0.001). Operative time (p = 0.001) was less for RRPN. No significant differences between TRPN vs. RRPN were noted for ischemia time (23.1 vs. 22.8 min, p = 0.313), blood loss (p = 0.772), positive margins (p = 0.590), complications (p = 0.537), length of stay (p = 0.296), ΔeGFR (p = 0.246), eGFR recovery to >90% (55.9 vs. 57.4%, p = 0.833), and lack of CKD upstaging (84.0 vs. 87.2%, p = 0.464). Pentafecta rates were not significantly different (TRPN 33.9 vs. RRPN 43.3%, p = 0.526). MVA revealed increasing RENAL score (OR 1.5, p < 0.001) and decreasing baseline eGFR (OR 2.4, p = 0.017) as predictive for lack of Pentafecta. CONCLUSIONS: TRPN and RRPN have similar quality outcomes, though RRPN may offer modest benefit for operative time and have utility in posterior tumors. Association of increasing RENAL score and decreased baseline eGFR with lack of Pentafecta suggests dominant role of non-modifiable factors.

The Case for Tailored Prostate Cancer Screening: An NCCN Perspective.

A preponderance of clinical evidence supports a significant public health benefit for screening and early detection of prostate cancer in selected men. The challenge lies in maximizing early diagnosis of potentially aggressive but curable disease while minimizing diagnosis and treatment of indolent disease. A tailored approach to population screening in appropriately counseled men, using an evidence-based strategy with judicious prostate-specific antigen (PSA) testing, will reduce prostate-cancer mortality yet limit overdetection of clinically insignificant disease. Use of newer biomarkers that increase specificity for prostate cancer detection, including percentage of free PSA, 4Kscore, prostate health index, prostate cancer antigen 3, and multiparametric MRI may be considered under certain circumstances.

Neoadjuvant therapy for localized and locally advanced renal cell carcinoma.

Neoadjuvant Targeted Molecular Therapy in the setting of localized and locally advanced renal cell carcinoma has emerged as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. Presurgical tumor reduction has been demonstrated in a number of studies including a recently published randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Nonetheless, most reports are small phase II clinical trials or retrospective reports. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for neoadjuvant strategies. This article reviews the current status and future prospects of neoadjuvant therapy in nonmetastatic renal cell carcinoma.

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database.

OBJECTIVE: To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. MATERIALS AND METHODS: We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. RESULTS: Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. CONCLUSIONS: pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions.

Can multiphase CT scan distinguish between papillary renal cell carcinoma type 1 and type 2?

OBJECTIVE: To investigate the utility of multiphase computed tomography (CT) and percutaneous renal mass biopsy (PRMB) in differentiating between papillary renal cell carcinoma (pRCC)-Type 1 and -Type 2, as emerging data have suggested differential enhancement patterns in different renal tumor histologies. MATERIAL AND METHODS: Retrospective analysis of 51 patients (23 pRCC-Type 1/28 pRCC-Type 2) who underwent multiphase CT followed by surgery from July 2011 to April 2016 was performed. Data were analyzed between subgroups based on histology. Multiphase CT was analyzed for tumor size, and attenuation [Hounsfield Units (HU)]. Change in HU (ΔHU) was calculated between noncontrast (NC), corticomedullary (CM), nephrographic (N), and delayed (D) phases. Subset analysis was carried out on patients who underwent PRMB prior to surgery. RESULTS: There was no difference in median tumor size (pRCC-Type 1 2.8 vs. pRCC-Type 2 2.6 cm, p=0.832). In addition to tumor size being similar between groups, distribution of tumor stages between groups was also similar (p=0.651). Greater proportion of high-grade tumors (III/IV) was noted in pRCC-Type 2 (42.9% vs. 8.7%) (p=0.011). There was no difference in HU values for NC (p=0.961), CM (p=0.118), N (p=0.277), and D (p=0.256) phases, and in ΔHU between CM-NC (p=0.278), N-NC (p=0.316), and D-NC (p=0.103). Thirteen patients underwent percutaneous biopsy, 11 of whom had diagnostic samples. Examination of 10/11 (90.9%) samples accurately predicted correct histology, and of 6/11 (54.5%) samples correctly identified high-vs. low-grade histology. CONCLUSION: Our findings suggest substantial overlap of CT findings, despite pRCC-Type 2 having greater proportion of high-grade tumors. Utility of CT is limited in the differentiation between pRCC subtypes. Patients with suggested pRCC on CT imaging being considered for a non-extirpative strategy should undergo PRMB for risk stratification.

Renal Functional Outcome of Partial Nephrectomy for Complex R.E.N.A.L. Score Tumors With or Without Neoadjuvant Sunitinib: A Multicenter Analysis.

BACKGROUND: Sunitinib might optimize the feasibility of partial nephrectomy (PN) for complex renal tumors with imperative indications. We compared the renal functional outcomes of patients with complex renal masses who had undergone sunitinib before PN with those of patients who had not required neoadjuvant sunitinib before PN. PATIENTS AND METHODS: We performed a multicenter retrospective analysis of patients with renal cell carcinoma who had undergone PN for a complex renal mass (R.E.N.A.L. nephrometry score, 10-12) and imperative indications from January 2012 to July 2014. Neoadjuvant sunitinib was used in cases for which PN was not considered feasible. The cohort was divided into those patients who had undergone PN without neoadjuvant sunitinib and those who had undergone PN after sunitinib (no-neoadjuvant vs. neoadjuvant). The change in tumor size and R.E.N.A.L. score were assessed. The primary outcome was the change in the estimated glomerular filtration rate (ΔeGFR) from preoperatively to the last postoperative follow-up visit. RESULTS: The data from 125 consecutive patients were analyzed (47 neoadjuvant and 78 no-neoadjuvant; median follow-up, 21 months). The neoadjuvant plus PN patients had had a greater median tumor size preoperatively (7.2 vs. 6 cm; P = .045). Sunitinib caused a significant decrease in the median tumor size (from 7.2 to 5.8 cm [19.4%]; P = .012) and R.E.N.A.L. score (from 11 to 9; P = .001). No significant differences were found between the neoadjuvant and no-neoadjuvant groups in the ischemia time (P = .413) or incidence of complications (P = .728). The median ΔeGFR was similar (neoadjuvant, 6.4; no-neoadjuvant, 6.1; P = .534). Linear regression analysis for factors associated with an increasing ΔeGFR demonstrated increasing age (estimate, -0.074; P = .009) increasing body mass index (estimate, -0.087; P = .043), and decreasing baseline eGFR (estimate, -0.104; P = .02) as significant factors. CONCLUSION: The use of neoadjuvant sunitinib might facilitate complex PN and result in renal functional outcomes similar to those of patients with a complex renal mass who had not required neoadjuvant sunitinib.

Weight Loss Following Radical Cystectomy for Bladder Cancer: Characterization and Effect on Survival.

INTRODUCTION: The purpose of this study was to evaluate the prevalence of postoperative weight loss (WL) following radical cystectomy (RC) and its association with mortality. Nutritional status is recognized as a potential modifiable risk factor for postoperative complications following RC for bladder cancer. The American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics recognize WL as a diagnostic measure for malnutrition. METHODS: Seventy-one patients underwent RC for bladder cancer between July 2008 and July 2013, in whom peri-operative weights were documented regularly. The primary predictor variable was substantial WL defined as ≥ 10% WL by postoperative month 1. Survival was estimated using Kaplan-Meier analysis; logistic regression was used for multivariate analyses. RESULTS: Mean postoperative WL at 2 weeks was 9.5 lbs (-5.2%), 14.3 lbs (-7.8%) at 1 month, 16.9 lbs (-9.0%) at 2 months, 12.6 lbs (-6.9%) at 3 months, and 8.9 lbs (-4.6%) at 4 months. Forty-two percent of patients met criteria for substantial WL. At 19 months median follow-up, the overall mortality rate was 31% (22 of 71), which rose to 64% (14 of 22) in patients who experienced substantial WL (P < .05). Substantial WL trended towards significance on multivariate analysis (P = .07). There was a significant decrease in 5-year survival in patients with ≥ 10% WL (log rank P < .05). CONCLUSIONS: Patients experience WL following RC, which may be indicative of malnutrition. Substantial WL may predict for poor overall survival. Prospective studies are needed to determine whether nutritional optimization can prevent significant WL and improve outcomes.

4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening.

A preponderance of clinical evidence supports a significant public health benefit for prostate-specific antigen (PSA)-based screening and early detection of prostate cancer in appropriately counseled and selected men. Population-based screening with PSA decreases prostate cancer mortality; however, because of relatively poor specificity, PSA-based screening may also increase the detection of clinically insignificant cancers that would otherwise never require treatment. Use of newer biomarkers that increase the specificity for prostate cancer detection may aid in risk stratification and the appropriate identification of men for prostate biopsy. The authors review the 4-kallikrein panel and 4K probability score.

Antimicrobial Practice Patterns for Urethroplasty: Opportunity for Improved Stewardship.

OBJECTIVE: To evaluate the current antimicrobial administration practice patterns for urethroplasty among genitourinary reconstruction experts. Improper use of antimicrobials is a global concern. The American Urological Association suggests that for perioperative antimicrobial prophylaxis, a single dose of intravenous cephalosporin be administered for open surgery involving the urinary system. No specific guidelines exist for urethral reconstruction. SUBJECTS AND METHODS: A 27-question survey was designed to assess antimicrobial practice patterns and was administered to 40 international members of the Society of Genitourinary Reconstructive Surgeons who commonly perform urethroplasty. RESULTS: The response rate was 85% (n = 34). Preoperative: Seventy-one percent order a urine culture preoperatively despite urine analysis result, and 32% do so 1 week prior. Regardless of catheter status, 41.8% use a urine bacteria threshold of 10K colony-forming units/mL to initiate treatment and ideal duration was 7 days in 35%. Meanwhile, 58.8% would not postpone surgery if preferred duration was not met, and 35% would empirically treat with antimicrobials if a urine culture was not performed. Perioperative: The majority administer 2 antimicrobials intraoperatively with 42% preferring aminoglycoside + penicillin regardless of. Postoperative: Eighteen percent to 24% of respondents continue intravenous antimicrobials for longer than 24 hours. Sixty-one percent administer oral antimicrobials until postoperative catheter removal (2-4 weeks), and the majority give additional antimicrobials at catheter removal. CONCLUSION: There is substantial variability and likely overuse of preoperative, perioperative, and postoperative antimicrobial administration for urethroplasty. Extended prophylactic duration is common postoperatively. Antimicrobial stewardship is our responsibility, and opportunity exists for improvement in antibiotic administration in urethral reconstruction. Prospective trials are requisite to establish guidelines for judicious yet effective regimens.

Association of Obesity, BMI, and Hispanic Ethnicity on Ambulatory Status in Children with Spinal Dysraphism followed near the California-Mexico Border.

PURPOSE: Evaluate the relationship between body mass index (BMI), overweight status (OW), or obesity (OB) and ambulatory status in a predominantly Hispanic population of children with spinal dysraphism (SD). METHODS: Retrospective data were extracted from records of 272 children and youth aged 0-24 years with a diagnosis of SD. Body mass index (BMI) and OW / OB rates were calculated for children 0-3 years, 4-11 years, and adolescents older than 11. RESULTS: Ethnicity was predominantly Hispanic (65.4%). No difference in mean BMI or OW / OB rate was found between ambulation groups (p = .20; p = .72). Mean BMI and OW / OB rate increased with increasing age in all groups (p < .001; p = .02). Forty-four percent of patients were OW / OB, which was greater among Hispanics (48.2%) compared with non-Hispanics [(35.2%), p = .03]. Female gender was a risk factor for increased BMI among Hispanics (p = .00). CONCLUSION: Despite no difference in ambulatory status, increasing BMI and OW / OB are associated with Hispanic ethnicity and increasing age.

Cytopathology and exocrine dysfunction induced in ex vivo rabbit lacrimal gland acinar cell models by chronic exposure to histamine or serotonin.

PURPOSE: Lacrimal immunohistopathology has diverse clinical presentations, suggesting that inflammatory mediators exert diverse influences. Chronic exposure to agonistic acetylcholine receptor autoantibodies has been studied previously; the present work addressed mediators that signal through other G protein-coupled receptors. METHODS: Acinus-like structures and reconstituted acinar epithelial monolayers from rabbit lacrimal glands were exposed to varying concentrations of histamine or 5-hydroxytryptamine (5-HT) for 20 hours. Net and vectorial beta-hexosaminidase secretion, cytosolic Ca(2+) (Ca(i)) elevation, apical recruitment of p150(Glued), actin microfilament meshwork organization, and ultrastructure were assessed. RESULTS: Histamine and 5-HT acutely stimulated beta-hexosaminidase secretion at lower, but not higher, concentrations. Neither of them acutely elevated Ca(i) levels. Both recruited p150(Glued) at concentrations that failed to induce secretion. Chronic exposure to 10 mM histamine inhibited carbachol (CCh)-induced beta-hexosaminidase secretion and prevented the formation of continuous monolayers; 1 mM 5-HT partially inhibited secretion at the apical medium. Neither altered secretion to the basal medium. Chronic exposure to histamine or 5-HT partially decreased CCh induced Ca(i) elevations and p150(Glued) recruitment, even at concentrations that did not inhibit secretion. Both expanded acinar lumina and thickened microfilament meshworks, and both caused homotypic fusion of secretory vesicles and formation of aqueous vacuoles in the apical and basal cytoplasm. Chronic exposure to forskolin, which activates adenylyl cyclase, induced similar cytopathologic changes but impaired secretion modestly and only at the highest concentration tested. CONCLUSIONS: Inflammatory mediators that signal through G protein-coupled receptors cause acinar cell cytopathology and dose-dependent reductions of CCh-induced beta-hexosaminidase secretion. Although agonistic acetylcholine receptor autoantibodies may cause pervasive functional quiescence, inflammatory mediators may cause varying degrees of exocrine dysfunction.