G. Joel DeCastro

Laparoscopic Lymphatic Sparing Varicocelectomy in Adolescents

PURPOSE Laparoscopic varicocelectomy is similar to an open Palomo repair. Both procedures involve en masse ligation of the internal spermatic cord, and both are associated with a 1% to 3% incidence of recurrence and up to a 30% incidence of hydroceles. We sought to determine the impact of lymphatic preservation on hydrocele formation and the success of varicocelectomy. MATERIALS AND METHODS We retrospectively evaluated 191 patients with a mean age of 15.2 years who underwent laparoscopic varicocelectomy and at least 6 months of followup. Patients were divided into 2 groups-those who had undergone a lymphatic sparing procedure and those who had undergone a nonlymphatic sparing technique. The incidence of recurrence/persistence, postoperative hydrocele formation and postoperative hydrocele requiring surgery or aspiration was analyzed. RESULTS A total of 174 laparoscopic lymphatic sparing procedures (132 patients, 42 bilateral) and 88 nonlymphatic sparing repairs (59 patients, 29 bilateral) were performed, with a mean followup of 26.1 months. Lymphatic sparing surgery was associated with a decreased incidence of postoperative hydrocele (3.4% vs 11.4%, p = 0.025). There was no significant difference in incidence of persistent or recurrent varicocele requiring reoperation following lymphatic sparing (5 sides, 2.9%) vs nonlymphatic sparing (4 sides, 4.5%) varicocelectomy (p = 0.736). CONCLUSIONS Laparoscopic lymphatic sparing varicocelectomy is preferable to an open or laparoscopic Palomo repair that does not preserve the lymphatics. It has a significantly lower incidence of postoperative hydroceles, especially those requiring surgical intervention, and still maintains a low incidence of persistence/recurrence. The procedure is especially advantageous for bilateral varicocelectomy.

Urothelial carcinoma of the bladder: definition, treatment and future efforts

The identification of patients with high-risk bladder cancer is important for the timely and appropriate treatment of this lethal disease. The understanding of the natural history of bladder cancer has improved; however, the criteria used to define high-risk disease and the relevant treatment strategies have remained the same for the past several decades, despite multiple large, randomized, prospective clinical trials that have evaluated the use of intravesical, surgical and systemic therapies. The genetic signature of high-risk bladder cancer has been a focus of investigation and has led to the discovery of potential molecular targets for disease identification, risk stratification and therapy. These advances, combined with a comprehensive risk assessment profile that incorporates available pathological and clinical characteristics, might improve the diagnosis and treatment of patients with bladder cancer.

The Impact of Mechanical Bowel Preparation on Postoperative Complications for Patients Undergoing Cystectomy and Urinary Diversion

PURPOSE The benefit of routine mechanical bowel preparation for patients undergoing radical cystectomy is not well established. We compared postoperative complications in patients who did or did not undergo mechanical bowel preparation before radical cystectomy. MATERIALS AND METHODS In 2008 a single surgeon (GDS) performed open radical cystectomy with an ileal conduit or orthotopic neobladder in 105 consecutive patients with preoperative mechanical bowel preparation consisting of 4 l GoLYTELY®. In 2009 radical cystectomy with an ileal conduit or orthotopic neobladder was performed in 75 consecutive patients without mechanical bowel preparation. A comprehensive database provided clinical, pathological and outcome data. RESULTS All patients had complete perioperative data available. The 2 groups were similar in age, Charlson comorbidity score, diversion type, receipt of neoadjuvant radiation or chemotherapy, blood loss, hospital stay, time to diet and pathological stage. Postoperative urinary tract infection, wound dehiscence and perioperative death rates were similar in the 2 groups. Clostridium difficile infection developed within 30 days of surgery in 11 of 105 vs 2 of 75 patients with vs without mechanical bowel preparation (p = 0.08). When adjusted for the annual hospital-wide C. difficile rate, the difference remained insignificant (p = 0.21). Clavien grade 3 or greater abdominal and gastrointestinal complications, including fascial dehiscence, abdominal abscess, small bowel obstruction, bowel leak and entero-diversion fistula, developed in 7 of 105 patients with (6.7%) vs 11 of 75 without (14.7%) mechanical bowel preparation (p = 0.08). CONCLUSIONS The use of mechanical bowel preparation for patients undergoing radical cystectomy with an ileal conduit or orthotopic neobladder does not seem to impact the rates of perioperative infectious, wound and bowel complications. Larger series with multiple surgeons are necessary to confirm these findings.

Peak Retrograde Flow: A Novel Predictor of Persistent, Progressive and New Onset Asymmetry in Adolescent Varicocele

PURPOSE The major indication for adolescent left varicocelectomy is testicular asymmetry. However, a period of observation is often recommended preoperatively to determine if the asymmetry resolves, persists or progresses. We investigated whether varicocele grade or the duplex Doppler ultrasound measurements of peak retrograde flow and mean vein diameter could be used as predictors of persistent, progressive or new onset asymmetry. MATERIALS AND METHODS Only patients with left varicoceles who had undergone at least 2 duplex Doppler ultrasounds without intervening surgery were included in the study. Grade of varicocele, peak retrograde flow and mean vein diameter were analyzed as possible determinants of catch-up growth, or persistent or new onset asymmetry. RESULTS A total of 77 patients (mean age 14.3 years, range 9 to 20) were identified with a mean observation period of 13.2 months. Of the patients 50 (65%) had 10% or greater asymmetry at the first measurement. Of patients with initial 20% or greater asymmetry 71% had persistent or worsening asymmetry on followup evaluation. All 14 patients with the combination of an initial peak retrograde flow 38 cm per second or greater and 20% or greater asymmetry had progressive asymmetry on followup examination. Peak retrograde flow was the only significant parameter of predictive value for persistent or worsening asymmetry (p = 0.032). CONCLUSIONS Peak retrograde flow can serve as a valuable tool in predicting persistent, progressive and new onset asymmetry. Varicoceles associated with a peak retrograde flow of 38 cm per second or greater and 20% or greater asymmetry should be considered for varicocelectomy at initial presentation. Patients with peak retrograde flow greater than 30 cm per second need to be monitored carefully. Those with peak retrograde flow less than 30 cm per second are less likely to require surgery.

An optimized procedure for exosome isolation and analysis using serum samples: Application to cancer biomarker discovery.

Exosomes are RNA and protein-containing nanovesicles secreted by all cell types and found in abundance in body fluids, including blood, urine and cerebrospinal fluid. These vesicles seem to be a perfect source of biomarkers, as their cargo largely reflects the content of parental cells, and exosomes originating from all organs can be obtained from circulation through minimally invasive or non-invasive means. Here we describe an optimized procedure for exosome isolation and analysis using clinical samples, starting from quick and robust extraction of exosomes with Total exosome isolation reagent, then isolation of RNA followed by qRT-PCR. Effectiveness of this workflow is exemplified by analysis of the miRNA content of exosomes derived from serum samples - obtained from the patients with metastatic prostate cancer, treated prostate cancer patients who have undergone prostatectomy, and control patients without prostate cancer. Three promising exosomal microRNA biomarkers were identified, discriminating these groups: hsa-miR375, hsa-miR21, hsa-miR574.

Adolescent varicocelectomy--is the potential for catch-up growth related to age and/or Tanner stage?

PURPOSE Adolescent varicocelectomy is associated with a 70% incidence of postoperative catch-up growth in boys with ipsilateral testicular hypotrophy. We determined whether preoperative patient age and Tanner stage were related to subsequent catch-up growth. In other words if patients are followed with a period of observation, will a window of opportunity be lost for achieving catch-up growth? MATERIALS AND METHODS We studied a total of 163 boys (mean age 15.1 years, range 10 to 24) with left or bilateral varicoceles who demonstrated 10% asymmetry or greater preoperatively, and had preoperative and postoperative testicular volume measurements available (using either ring orchidometer or ultrasound). Of these patients 59 also had preoperative Tanner stage recorded. RESULTS Of the patients with preoperative left hypotrophy 69% had achieved catch-up growth at last followup (mean followup 28 months). When treated as a continuous variable, or when divided into general prepubertal vs postpubertal groupings, age at surgery was not significantly associated with catch-up growth. Similarly, there was no significant difference in catch-up growth associated with grade of varicocele, duration of postoperative followup or presence of unilateral left vs bilateral varicocele. No association with Tanner stage was found, although the patient numbers were too small to draw any statistically significant conclusions. CONCLUSIONS The prevalence of testicular catch-up growth after varicocelectomy is high, even for patients in their early 20s. Among males 10 to 24 years old there is no specific age or Tanner stage that offers the best opportunity for catch-up growth.

Validation of a frailty index in patients undergoing curative surgery for urologic malignancy and comparison with other risk stratification tools.

OBJECTIVE To retrospectively validate and compare a modified frailty index predicting adverse outcomes and other risk stratification tools among patients undergoing urologic oncological surgeries. MATERIALS AND METHODS The American College of Surgeons National Surgical Quality Improvement Program was queried from 2005 to 2013 to identify patients undergoing cystectomy, prostatectomy, nephrectomy, and nephroureterectomy. Using the Canadian Study of Health and Aging Frailty Index, 11 variables were matched to the database; 4 were also added because of their relevance in oncology patients. The incidence of mortality, Clavien-Dindo IV complications, and adverse events were assessed with patients grouped according to their modified frailty index score. RESULTS We identified 41,681 patients who were undergoing surgery for presumed urologic malignancy. Patients with a high frailty index score of >0.20 had a 3.70 odds of a Clavien-Dindo IV event (CI: 2.865-4.788, P<0.0005) and a 5.95 odds of 30-day mortality (CI: 3.72-9.51, P<0.0005) in comparison with nonfrail patients after adjusting for race, sex, age, smoking history, and procedure. Using C-statistics to compare the sensitivity and specificity of the predictive ability of different models per risk stratification tool and the Akaike information criteria to assess for the fit of the models with the data, the modified frailty index was comparable or superior to the Charlson comorbidity index but inferior to the American Society of Anesthesiologists Risk Class in predicting 30-day mortality or Clavien-Dindo IV events. When the modified frailty index was augmented with the American Society of Anesthesiologists Risk Class, the new index was superior in all aspects in comparison to other risk stratification tools. CONCLUSION Existing risk stratification tools may be improved by incorporating variables in our 15-point modified frailty index as well as other factors such as walking speed, exhaustion, and sarcopenia to fully assess frailty. This is relevant in diseases such as kidney and prostate cancer, where surveillance and other nonsurgical interventions exist as alternatives to a potentially complicated surgery. In these scenarios, our modified frailty index augmented by the American Society of Anesthesiologists Risk Class may help inform which patients have increased surgical complications that may outweigh the benefit of surgery although this index needs prospective validation.

Who Really Benefits From Nephron-sparing Surgery?

OBJECTIVE To analyze the influence of preoperative renal function on postoperative renal outcomes after radical nephrectomy (RN) and nephron-sparing surgery (NSS) for malignancy in patients stratified according to preoperative chronic kidney disease (CKD) stage and surgical extent (NSS vs RN). PATIENTS AND METHODS Retrospective review of patients undergoing renal surgery for localized renal masses stratified by surgical extent and preoperative CKD stage based on glomerular filtration rate (GFR) level: stage I (>90 mL/min/1.73 m(2)), stage II (60-89 mL/min/1.73 m(2)), and stage III (30-59 mL/min/1.73 m(2)). Survival analysis for significant renal impairment was based on freedom from the development of new-onset GFR <30 or <45 mL/min/1.73 m(2). RESULTS A total of 1306 patients were included in the analysis with preoperative CKD stage I (27.9%), II (52.1%), and III (20.1%); 41.3% and 58.7% underwent NSS and RN, respectively. NSS was associated with a lower annual rate of GFR decline in preoperative CKD stage-I (P = .028) and stage-II patients (P = .018), but not in CKD stage-III patients (P = .753). Overall, 5.0% and 15.0% developed new-onset GFR <30 mL/min/1.73 m(2) and <45 mL/min/1.73 m(2), respectively. There was no difference in the probability of developing significant renal impairment between NSS and RN in CKD stage-I or -III patients, whereas only in CKD stage-II patients was the surgical extent independently associated with development of significant renal impairment (RN: odds ratio, 9.0; P = .042 for GFR <30 mL/min/1.73 m(2) and odds ratio, 2.3; P = .003 for GFR <45 mL/min/1.73 m(2)). CONCLUSION Compared with RN, NSS is associated with a lower rate of GFR decline for preoperative CKD stage-I and -II patients, but only CKD stage-II patients demonstrated a decreased risk of developing significant renal impairment.

Adolescent varicocelectomy: Postoperative catch-up growth is not secondary to lymphatic ligation

PURPOSE The major indication for adolescent varicocelectomy is testicular asymmetry with the left testicle smaller than the right. Catch-up growth following surgery is one of the parameters used to assess efficacy of surgery. However, it is not clear whether this represents true tissue growth or increased interstitial fluid secondary to lymphatic obstruction. The purpose of this study was to compare catch-up growth in patients who underwent varicocelectomy with and without lymphatic preservation. MATERIALS AND METHODS We retrospectively analyzed the outcomes of 136 boys (mean age 15.1years) who had 10% or greater preoperative testicular asymmetry and underwent varicocelectomy between 1997 and 2006. Surgery was either a laparoscopic nonlymphatic sparing or laparoscopic lymphatic sparing varicocelectomy. All patients had pre- and postoperative ultrasound volume measurements at least 6months following surgery. The groups were compared for incidence of postoperative catch-up growth, achieving less than 10% testicular asymmetry. RESULTS After a mean follow up of 24.7months, catch-up growth was achieved in 62.8% of patients. There was no significant difference between the groups in regard to catch-up growth (51.7% vs 66.3%, P=0.193). CONCLUSIONS Since no significant difference was found between the laparoscopic nonlymphatic sparing and laparoscopic lymphatic sparing varicocelectomies, we conclude that lymphatic obstruction is not the cause of catch-up growth.

Cost-effectiveness of neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer

OBJECTIVES To determine the costs of treatment and the duration of survival, adjusted for quality of life, for patients with muscle-invasive bladder cancer treated with immediate radical cystectomy (RC) or with neoadjuvant chemotherapy (NAC) with intent for subsequent RC. METHODS AND MATERIALS A retrospective review of our institutional review board-approved database identified patients with muscle-invasive bladder cancer treated at our institution from 2004 to 2011. Patients were divided into those receiving RC alone and those receiving NAC before planned RC. Patients who refused RC following NAC were included in an intention-to-treat analysis. Survival duration was converted to quality-adjusted life years (QALYs), and costs of treatment per QALY were determined. RESULTS A total of 119 patients (65.4%) received RC alone and 63 (34.6%) received NAC, 38 of whom proceeded to cystectomy as planned. Mean total costs were