A data-driven concept schema for defining clinical research data needs.

OBJECTIVES: The Patient, Intervention, Control/Comparison, and Outcome (PICO) framework is an effective technique for framing a clinical question. We aim to develop the counterpart of PICO to structure clinical research data needs. METHODS: We use a data-driven approach to abstracting key concepts representing clinical research data needs by adapting and extending an expert-derived framework originally developed for defining cancer research data needs. We annotated clinical trial eligibility criteria, EHR data request logs, and data queries to electronic health records (EHR), to extract and harmonize concept classes representing clinical research data needs. We evaluated the class coverage, class preservation from the original framework, schema generalizability, schema understandability, and schema structural correctness through a semi-structured interview with eight multidisciplinary domain experts. We iteratively refined the schema based on the evaluations. RESULTS: Our data-driven schema preserved 68% of the 63 classes from the original framework and covered 88% (73/82) of the classes proposed by evaluators. Class coverage for participants of different backgrounds ranged from 60% to 100% with a median value of 95% agreement among the individual evaluators. The schema was found understandable and structurally sound. CONCLUSIONS: Our proposed schema may serve as the counterpart to PICO for improving the research data needs communication between researchers and informaticians.

Pathological confirmation of nerve-sparing types performed during robot-assisted radical prostatectomy (RARP).

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Incremental nerve-sparing techniques (NSTs) improve postoperative erectile function after robot-assisted radical prostatectomy (RARP). However, there are no studies to date that histologically confirm the surgeon intended NST. Thus, in the present study, we histologically confirmed that the surgeon performed the nerve preservation as his intended NSTs during RARP. Also, we found that there was more variability in fascia width outcome on the left side compared with the right. Therefore, when performing nerve preservation on the surgeon's non-dominant side, we need to pay more close attention. OBJECTIVES: To confirm that the surgeon achieved true intended histological nerve sparing during robot-assisted radical prostatectomy (RARP) by studying RP specimens. To aid the novice robotic surgeon to develop the skills of RARP. PATIENTS AND METHODS: Between June 2008 and May 2009, 122 consecutive patients underwent RARP by a single surgeon (K.K.B.). The degree of nerve sparing (wide resection [WR], interfascial nerve sparing [ITE-NS], intrafascial nerve sparing [ITR-NS]) on both sides was recorded. The posterior sectors of RP specimens from distal, mid, and proximal parts were evaluated. Fascia width (FW) of each position in RP specimens were compared across nerve-sparing types (NSTs). FW was recorded at 15 ° intervals (3-9 o'clock position), measured as the distance between the outermost prostate gland and surgical margin. The slides were reviewed by an experienced uropathologist who was 'blinded' to the NST. RESULTS: In all, 93 men were included. The overall mean (sd) FW was the greatest in the order of WR, ITE-NS, and ITR-NS, at 2.42 (1.62), 1.71 (1.40) and 1.16 (1.08) mm, respectively (P < 0.001). FW was statistically significantly correlated with the surgical technique used. When the surgeon intended to perform various levels of nerve sparing, these were reflected in the FW. Interestingly, the left-side FW showed more variability than the right side. We suspect that this was a result of the surgeon's right-hand dominance. Erectile function (EF) recovery rate according to NST was 88.9%, 77.3%, 65.6%, 56.3%, and 0% in bilateral ITR-NS, ITR-NS/ITE-NS, bilateral ITE-NS, ITE-NS/WR, and bilateral WR, respectively. To further validate and confirm these preliminary findings, additional studies involving multicentre cohorts would be required. CONCLUSIONS: The surgeon intended dissection and FW correlate, with ITR-NS providing the narrowest FW and the EF recovery rate was the highest in bilateral ITR-NS. There was more variability in FW outcome on the left side than the right. The novice robotic surgeon should consider this variability when performing RARP. It may have implications for technique improvement on nerve preservation for EF.

Partial nephrectomy online: a preliminary evaluation of the quality of health information on the Internet.

UNLABELLED: What's known on the subject? and What does the study add? Patients are highly likely to access the Internet for health information, and studies have reported that inaccurate or low-quality information may alter patients' expectations and negatively impact informed decision-making. In a unique collaboration with the Health On the Internet (HON) Foundation, we evaluated the top 20 search results for the urology search term 'partial nephrectomy,' and identified the highest and lowest scoring criteria to increase awareness of areas of concern and improvement. OBJECTIVE: To further evaluate the quality of information available on the Internet with regard to the management of localized renal cancer, we evaluated websites providing information on 'partial nephrectomy' in conjunction with the Health On the Internet (HON) Foundation. Many patients now utilize the Internet as a resource to provide further information on disease, treatments and outcomes, and health information on the Internet is largely unregulated. Inaccurate information may contribute to unrealistic expectations and dissatisfied patients. PATIENTS AND METHODS: A google.com search identified the top 30 websites for the search term 'partial nephrectomy'. The HON Foundation evaluated each website according to the eight principles for Health on the Internet code of conduct (HONcode) certification and reported the overall frequency of certification, as well as individual website compliance with each of the principles. RESULTS: Overall, seven (23.3%) of 30 websites met the requirements of HONcode certification and an additional two (6.7%) websites were under review to maintain their certification based on updating their resources. The remaining 21 (70%) websites did not meet the standards for certification. The lowest performing criteria included proper citation of medical information and a clear distinction of advertising from editorial content. CONCLUSIONS: The low rate of HONcode compliance for these websites illustrates the poor quality of information that patients may encounter when researching options for nephron-sparing surgery, which may have a significant impact on patient decision-making and treatment choices. Physicians should be aware of the quality of Internet resources and how to best use these tools to help guide patients to websites with valid information.

Socioeconomic and clinical factors influence the interval between positive prostate biopsy and radical prostatectomy.

OBJECTIVE: To examine socioeconomic and clinical factors that may predict a longer interval between prostate biopsy and radical prostatectomy (RP). METHODS: The Columbia University Urologic Oncology Database was queried for patients who underwent RP from 1990-2010. Time to surgery (TTS) was defined as the period between the most recent positive prostate biopsy and date of surgery. Clinical factors examined included: age, D'Amico risk group, year of surgery, body mass index, and comorbidities. Socioeconomic factors included race/ethnicity, relationship status, income, and distance to treatment center. The relationship between clinical/socioeconomic factors and TTS was evaluated using univariate and multivariate regression models. RESULTS: Two-thousand five-hundred seventy-three patients were included in the analysis. Median TTS was 48 days (IQR 35-70, range 43-1103), and 71% of patients underwent RP within 60 days after the most recent positive biopsy. On multivariate analysis, living further from the medical center was associated with shorter TTS (P = .01), whereas more recent year of surgery (P = .01), comorbid cardiovascular disease (P = .007), African-American (P = .005) or Hispanic race (P = .005), divorced relationship status (P = .01), and lower income (P = .003) were all associated with longer TTS. CONCLUSION: Patients often experience widely variable intervals between the diagnosis and treatment of localized prostate cancer. Longer intervals before surgery may point to disparities in access to prostate cancer care, and not increased decision-making time by the patient.

Comparison of biochemical failure definitions for predicting local cancer recurrence following cryoablation of the prostate.

BACKGROUND: Various definitions of biochemical failure (BF) have been used to predict cancer recurrence following prostate cryoablation. However to date, none of these definitions have been validated for this use. We have reviewed several definitions of BF to determine their accuracy in predicting biopsy-proven local recurrence following prostate cryoablation. METHODS: The Columbia University Urologic Oncology Database was queried for patients who underwent prostate cryoablation between 1994 and 2010, and who subsequently underwent surveillance biopsy due to clinical suspicion of prostate cancer recurrence. Serial postoperative prostate-specific antigen (PSA) results were used to determine BF according to various definitions of BF. Biopsy results were used to determine local recurrence. Sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curve area were calculated for each of the BF definitions. RESULTS: A total of 110 patients met inclusion criteria for the study. These patients were treated with primary full-gland (n = 38), primary focal (n = 24), or salvage cryoablation (n = 48). On surveillance biopsy, 66 patients (60%) were found to have locally recurrent prostate cancer. The most accurate BF definition overall was PSA nadir plus 2 ng/ml (Phoenix definition), with sensitivity, specificity, and ROC curve area of 68%, 59%, and 0.64, respectively. CONCLUSIONS: Overall, the Phoenix definition best predicted local cancer recurrence following prostate cryoablation. These preliminary data may be useful for researchers evaluating the short-term efficacy of cryoablation, and for urologists assessing their patients for potential cancer recurrence.

Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer.

BACKGROUND: It is becoming increasingly evident that microRNAs (miRNAs) are associated with the development and progression of prostate cancer (PCa). METHODS: We examined the hypothesis that plasma miRNA levels can differentiate patients by aggressiveness in 82 PCa patients. Taqman based quantitative RT-PCR assays were performed to measure copy number of target miRNAs. RESULTS: miR-20a was significantly overexpressed in plasma from patients with stage 3 tumors compared to stage 2 or below (P = 0.03). The expression levels for miR-20a and miR-21 were significantly increased in patients with high risk CAPRA scores (16,623 and 1,595 copies, respectively). Significantly increased miR-21 and miR-145 expression were observed for patients with intermediate or high risk D'Amico scores compared to patients with low risk scores (P = 0.047 and 0.011, respectively). The relapse rates for CAPRA scores ranged from 1.9% for low risk to 9.5% for intermediate risk and to 22.2% for high risk patients (P = 0.023). For D'Amico scores, the relapse rates ranged from 0.0% for low risk to 7.4% for intermediate risk and 17.6% for high risk patients (P = 0.039). Expression of miR-21 and miR-221 significantly differentiated patients with intermediate risk from those with low risk CAPRA scores (AUC = 0.801, P = 0.002). Four miRNAs (miR-20a, miR-21, miR-145, and miR-221) could also distinguish high versus low risk in PCa patients by D'Amico score with an AUC of 0.824. CONCLUSIONS: These preliminary data suggest that altered plasma miRNAs may be useful predictors to distinguish PCa patients with varied aggressiveness. Further larger studies to validate this promising finding are warranted.

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion.

UNLABELLED: What's known on the subject? and What does the study add? In an array of urological and non-urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20-year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI-positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI-positive disease have overall survival outcomes similar to those of patients with muscle-invasive LVI-negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC. OBJECTIVE: To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified. These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log-rank tests and Cox proportional hazards regression models. Actuarial survival curves were calculated using the Kaplan-Meier method. RESULTS: LVI was observed in 68 patients (32.2%). The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5- and 10-year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively. In multivariate analysis, age, race and LVI were independent predictors of overall survival. CONCLUSIONS: The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC. LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options. With confirmation from large international studies, inclusion of LVI in the tumour-node-metastasis staging system for UTUC should be considered.

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer.

BACKGROUND: Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2-T4aN0-N2M0 bladder cancer. METHODS: In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum-based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin-based chemotherapy compared with carboplatin-based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin-based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01-112.2). CONCLUSION: In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum-based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin- or carboplatin-based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy.

DNA methylation changes correlate with Gleason score and tumor stage in prostate cancer.

DNA methylation, a widely used epigenetic mark, has been associated with many tumors. However, few studies have addressed the role of cell-free plasma DNA methylation in discriminating aggressive prostate cancer (PCa) from indolent cases. We conducted a case series and a case-control study among histologically confirmed stage II/III cases and matched controls recruited at Columbia University Medical Center. The aim of this study was to investigate whether plasma DNA methylation levels are appropriate surrogate biomarker of PCa tumor tissue levels and whether these markers are associated with worse clinicopathological tumor characteristics, which correlate with poorer prognosis. Quantitative pyrosequencing was used to detect methylation levels of p16 (CDKN4A), APC, GSTP1, and LINE-1 in 24 pairs of prostate tumor and adjacent tissues, as well as 27 plasma samples of PCa patients and 24 of controls. DNA methylation levels were significantly higher in tumor tissue than in adjacent nontumor tissue for p16 (CDKN4A), GSTP1, and APC; GSTP1 had a higher average percentage methylation in tumor tissue (38.9%) compared with p16 (CDKN4A) (5.9%) and APC (14.5%). GSTP1, p16 (CDKN4A), and APC methylation in tumor tissue was statistically significantly higher for cases with Gleason score ≥7 compared with those with Gleason score <7 [49.0% vs. 21.9% (p=0.01), 6.6% vs. 4.5% (p=0.04), and 19.1% vs. 7.4% (p=0.02), respectively]. Plasma LINE-1 methylation levels were higher in those with higher Gleason (67.6%) than in those with Gleason's below 7 (64.6%, p=0.03). Significant plasma-tissue correlations were observed for GSTP1 and LINE-1 methylation. These data, although preliminary, suggest that aberrant methylation may be a useful marker to identify PCa patients with clinically aggressive disease.

Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis.

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high-risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes. OBJECTIVE: • To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: • We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution. • Clinical and pathological features were compared between men undergoing RP ≤ 60, 61-90 and >90 days from the time of prostate biopsy. • A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)-free rates were assessed using the Kaplan-Meier method. RESULTS: • Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of ≤ 60, 61-90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery. • The 5-year survival rate was similar among the three groups (78-85%, P= 0.11). • In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African-American race were all at higher risk for developing BCR. • A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model. CONCLUSIONS: • A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR-free survival. • Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes.

Tumour diameter and decreased preoperative estimated glomerular filtration rate are independently correlated in patients with renal cell carcinoma.

OBJECTIVE: To examine the relationship between tumour diameter and estimated GFR (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC were identified in the Columbia Urologic Database. eGFR was calculated using the modification of diet in renal disease equation using demographic data and preoperative serum creatinine values. Data on patient demographics, tumour characteristics, and comorbidities were analyzed using univariate and multivariate regression analysis. RESULTS: Mean (sd, range) tumour diameter was 5.29 (3.8, 0.3-29) cm. Mean (sd, range) eGFR was 75 (23.4, 3-173) mL/min per 1.73 m(2) . In multivariate regression analysis, tumour diameter independently predicted decreased preoperative eGFR (coefficient, -0.513; P= 0.008) when controlling for hypertension and race. Consistent with this, decreased preoperative eGFR independently predicted increased tumour diameter (coefficient, -0.013; P= 0.007) when controlling for race, histology and smoking status. CONCLUSION: Tumour diameter and decreased preoperative eGFR are independently correlated in patients with RCC.

Vitamin D deficiency in the urological population: a single center analysis.

PURPOSE: Vitamin D has a well-known role in calcium metabolism and bone health. It may also help prevent a number of chronic diseases, including cardiovascular disease, diabetes and malignancies such as breast, colorectal and prostate cancer. To our knowledge the prevalence of vitamin D deficiency has never been reported in the general urological population. We evaluated the vitamin D status of this population at a large academic center. MATERIALS AND METHODS: We retrospectively reviewed the records of 3,763 male and female patients from a urology database at a single academic institution. Patients were identified whose levels of serum 25-hydroxyvitamin D were measured for the first time between 1997 and 2010. We determined the prevalence of normal--greater than 30, insufficient--20 to 29 and deficient--less than 20 ng/ml 25-hydroxyvitamin D. Logistic regression analysis was performed to identify risk factors for vitamin D deficiency. RESULTS: Overall 2,559 patients (68%) had suboptimal 25-hydroxyvitamin D (less than 30 ng/ml), of whom 1,331 (52%) were frankly deficient (less than 20 ng/ml) in the vitamin. Vitamin D deficiency was more common in patients younger than age 50 years (44.5%), black (53.2%) and Hispanic (41.6%) patients (p <0.001), and patients without an existing urological malignancy (35.4%, p <0.001). On multivariate analysis race, age, season and cancer diagnosis were independent predictors of vitamin D status. CONCLUSIONS: Vitamin D deficiency is extremely common in urological patients at a major urban medical center. Urologists should consider recommending appropriate supplementation during the initial assessment of all patients.

Impact of HMG-CoA reductase inhibitor (statin) use on blood loss during robot-assisted and open radical prostatectomy.

BACKGROUND AND PURPOSE: In addition to their lipid lowering effects, HMG-CoA reductase inhibitors (statins) have been shown to exert antithrombotic effects through downregulation of the coagulation cascade. Because statin use is widespread, it is important to understand the impact of these drugs on blood loss (BL) during surgery. We studied the impact of statin use on BL during robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP). PATIENTS AND METHODS: A retrospective review was conducted of a database approved by the Institutional Review Board for patients who underwent RARP or ORP at a single academic institution. Patients were categorized as statin-users or statin-naïve at the time of surgery. Patient demographic information was recorded as was perioperative data, including preoperative and postoperative hematocrit (Hct) value. BL was defined as % Hct change presurgery vs postsurgery. In addition, the outcome of ≥10% drop in Hct was studied. The t test and chi-square analysis were used to compare variables across statin use groups. Univariate and multivariable logistic regression analyses were used to identify factors that impacted BL. RESULTS: From 1987 to 2010, 3578 patients underwent prostatectomy for prostate cancer (RARP=945 and ORP=2633). Of these, 676 men were identified as statin-users and 2902 as statin-naïve. Mean patient age was 60.2±7.0 years. Statin-users were found to be older (P<0.001), have lower mean preoperative prostate-specific antigen (PSA) levels (P=0.002), and have higher pathologic Gleason sum scores (P<0.001). For ORP, statin use was associated with increased BL with Hct % change of 20.7% for users vs18.6% for nonusers, (P<0.001). For RARP, no significant change in Hct was seen with statin use with % changes of 12.6% and 12.5%, respectively (P=0.9). When controlling for age, Gleason sum, surgeon, date of surgery and PSA level, statin use was associated with increased BL (P=0.04). CONCLUSION: Even when controlling for age, Gleason sum, surgeon, date of surgery, and PSA, statin use is associated with increased BL during RP. This information may impact preoperative planning and patient counseling for men who are taking statins while preparing for RP.

Comparison of distal ureteral management strategies during laparoscopic nephroureterectomy.

BACKGROUND AND PURPOSE: The optimal approach for management of the distal ureter and bladder cuff (DUBC) during laparoscopic nephroureterectomy (LNU) for upper-tract transitional-cell carcinoma (TCC) is controversial. We describe our contemporary experience with LNU and compare several approaches to the DUBC. PATIENTS AND METHODS: A retrospective analysis was performed on 36 patients undergoing LNU. Three approaches to the DUBC were used: Open resection (OR), complete laparoscopic dissection and suture reconstruction (LR), and laparoscopic dissection with DUBC stapling (LS). Patient demographics and intraoperative, perioperative, and pathologic variables were compared. Estimated 2-year recurrence-free survival (RFS) was calculated. RESULTS: A total of 36 patients were analyzed: 10 OR, 12 LR, and 14 LS. The mean age was 69.6 years with a mean follow-up of 15 months. The LR and LS groups had significantly shorter operative times compared with the OR group (163 and 152 vs 276 minutes, respectively (P<0.05). The LR group had the shortest mean length of stay compared with the OR and LS groups (2.0 vs 3.5 and 2.7 days, respectively, P<0.05). No patient had a complete ureteral orifice, but a cystoscopically appreciable remnant of the resected ureteral orifice was noted in 50% of the LS group vs none with the LR and OR groups (P<0.05). The estimated 2-year RFS was 65% for the entire cohort with no significant differences among groups. CONCLUSIONS: Complete laparoscopic resection of the DUBC is feasible, particularly in low-stage, low-grade upper tract TCC and provides benefits such as shorter operative times and length of stay compared with an open bladder cuff excision.

Impacting factors for recovery of erectile function within 1 year following robotic-assisted laparoscopic radical prostatectomy.

INTRODUCTION: Neurovascular bundle preservation generally results in good postoperative sexual function after radical prostatectomy. However, erectile function (EF) after radical prostatectomy is still a significant concern. The same surgical technique often results in different EF outcomes. AIM: We evaluated factors that correlate with recovery of EF within 1 year after robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: From January 2008 to May 2009, 145 consecutive patients underwent RALP by one surgeon. Patients were followed postoperatively at 3-month intervals and assessed for EF recovery, defined as an erection sufficient for penetrative intercourse with satisfaction. Baseline demographics, medical comorbidities, degree of nerve sparing, and perioperative and postoperative variables were recorded. Univariate and multivariate analyses were used to determine factors associated with EF recovery. MAIN OUTCOME MEASURES: Postoperative sexual outcomes were attained prospectively via our erectile state questionnaire. RESULTS: Complete follow-up EF data were available on 89 men. Within 1-year follow-up, 56 men (62.9%) recovered EF and 33 men (37.1%) did not. In univariate logistic regression analysis, race (black), diabetes mellitus, hyperlipidemia, and clinical T2 carcinoma of the prostate were associated with diminished EF. Higher-preoperative Sexual Health Inventory for Men score and incremental nerve sparing (enhanced lateral prostatic fascia sparing) were associated with higher odds of recovering potency. In multivariate analysis, hyperlipidemia was primary comorbidity associated with diminished EF, and bilateral nerve sparing with a minimum unilateral-enhanced status was the impacting factor for EF recovery within 1 year after surgery. CONCLUSIONS: Bilateral nerve preservation with a minimum unilateral-enhanced status is associated with improved recovery of EF, and hyperlipidemia is a significant negative predictive factor of postoperative EF recovery within 1 year following RALP. Therefore, it is important to control hyperlipidemia as well as to use the proper surgical technique in maximizing EF recovery within 1 year after radical prostatectomy.

Gleason score concordance on biopsy-confirmed prostate cancer: is pathological re-evaluation necessary prior to radical prostatectomy?

OBJECTIVES: • Gleason sum from prostate biopsy (bGS) is an important tool in classifying severity of disease, ultimately influencing clinical management. • Commonly, pathology specimens are re-evaluated internally prior to surgery. • We evaluate agreement of bGS with prostatectomy Gleason sum (pGS) and the impact of re-grading on prediction of true underlying tumor architecture. MATERIALS AND METHODS: • Retrospective analysis of men who underwent robotic-assisted radical prostatectomy (RARP) by two surgeons from 2005-2009. Initial transrectal ultrasound (TRUS) biopsy demonstrated carcinoma at an outside lab. Specimens were re-evaluated by our GU pathologists prior to surgery. Biopsy data were correlated with pGS. • Kappa (κ) statistics for agreement and linear regression analyses were used for categorical variables. Coefficient of concordance was used for continuous variables. RESULTS: • 100 patients had 331 positive biopsies. Agreement (κ) for bGS between outside labs and our pathologists was 0.55 (p < 0.001). • Internal read was twice as likely to upgrade vs. downgrade outside bGS (23% vs. 11%). • When re-evaluation resulted in a change in bGS, agreement with pGS was κ= 0.29, vs. κ=-0.04 for agreement of initial (outside) bGS with pGS. • When no change was made to bGS, agreement with pGS was κ= 0.40 (p < 0.001). CONCLUSION: • Good reproducibility seen between outside labs and our institution on bGS. Internal pathology re-reads correlated better with pGS than original community bGS. When re-reads result in a change in bGS, there is a marked improvement in prediction of underlying tumor architecture confirming the value of re-evaluating all external biopsies prior to definitive surgery.

Comparison of two core biopsy techniques before and after laparoscopic cryoablation of small renal cortical neoplasms.

INTRODUCTION: Cryoablation is an acceptable treatment option for small renal cortical neoplasms (RCN). Unlike extirpative interventions, intraoperative needle biopsy is the only pathologic data for ablated tumors. It is imperative that sampled tissue accurately captures pathology. We studied the optimal intraoperative needle core biopsy protocol for small RCN during laparoscopic renal cryoablation (LCA). METHODS: Patients with RCN<4cm underwent intraoperative biopsy during LCA. Four biopsy cores were taken per tumor, 2 before and 2 after LCA by using both a standard and modified technique. Standard technique: needle biopsy device was deployed after insertion into the renal tissue at a depth of 5mm. Modified technique: needle biopsy device was deployed 1mm outside of the renal tissue. Biopsies were examined and compared with reference standard pathology. Percentage agreement was calculated across biopsy types (standard vs. modified) and time points (pre- vs. postcryoablation). Logistic regression was used to identify factors impacting biopsy accuracy. RESULTS: Thirty patients with 33 RCNs underwent LCA. The mean patient age was 69.1±8.0yrs, and mean tumor size was 2.3±0.7cm. No significant bleeding resulted from biopsies. A definitive diagnosis was made in 31/33 RCNs (94.0%). Ten tumors (30.3%) were benign, 21 (63.7%) were malignant, and 2 (6.0%) were nondiagnostic. Biopsy length was significantly longer using the standard vs. modified technique with mean lengths of 9.3mm vs. 7.0mm, respectively (P=.02). Highest agreement was seen in preablation biopsies (90.3%). A significant association with agreement was seen for younger age (P=.05) and larger tumor size (P=.02). CONCLUSIONS: Younger age and larger tumor size were associated with improved accuracy. Preoperative sampling resulted in superior accuracy and the standard technique resulted in significantly longer cores. Use of preablation standard biopsy technique may result in the most accurate pathologic diagnosis for patients undergoing cryoablation for small RCNs.

An evaluation of patient selection criteria on predicting progression-free survival after primary focal unilateral nerve-sparing cryoablation for prostate cancer: recommendations for follow up.

PURPOSE: Focal cryoablation targets unilateral disease, sparing healthy tissue and the ipsilateral neurovascular bundle. Given half the prostate is spared, proper patient selection is imperative to optimize outcomes. We report focal cryotherapy outcome data and evaluate the accuracy of the 2007 Task Force patient selection criteria at predicting disease recurrence. MATERIALS AND METHODS: This is a retrospective patient chart review from a single academic institution. Inclusion criterion is having unilateral prostate cancer treated with primary hemicryoablation. Patients were stratified using the Task Force selection criteria. Exclusion criterion is having had past radiation or hormone therapy. Progression-free survival was calculated using follow-up TRUS biopsy (biopsy done with transrectal ultrasound) and serial prostate-specific antigen (PSA) results (Phoenix criteria). Kaplan-Meier curves were constructed and Cox regression analyses performed, comparing outcomes across patient selection cohorts. RESULTS: From 2002 to 2009, 77 men underwent primary focal cryosurgery: mean age, 69.5 (SD, 6.7) years; median follow-up time, 24 months (range, 0-87 months); mean precryosurgical PSA, 6.5 (SD, 4.9) ng/mL; median Gleason score, 6 (range, 5-8). There were 44, 31, and 2 men who had D'Amico low-, intermediate-, and high-risk disease, respectively. Seventeen men met Focal Task Force Selection Criteria. After treatment, 22 patients underwent prostate biopsy for suspicion of recurrent disease. Of the 22 patients, 10 (45.5%) had confirmed prostate cancer. Of the 10 patients, 2 had ipsilateral disease, 7 had contralateral disease, and 1 had bilateral disease. Overall biochemical and pathological progression-free survival rates were 72.7% and 87%. The cumulative incidence of biochemical disease progression, using the Kaplan-Meier method, was greater than 75% at 3 years for men with more than 2 positive preoperative biopsy cores and greater than 50% at 5 years for men with 2 or less positive preoperative biopsy cores. No survival differences were seen across cohorts. Pretreatment PSA level, pretreatment Gleason score, number positive cores, and total tumor length were associated with disease progression. CONCLUSIONS: Focal cryotherapy is a promising option for carefully selected patients, although optimization of inclusion criteria is required. Current selection criteria are associated with cancer-free survival. Given no accurate definitions for biochemical failure after focal cryotherapy exist combined with our high biochemical failure rate, mandating 12-month follow-up TRUS biopsy may improve accurate detection of cancer progression. Further follow up will determine optimal patient selection criteria and follow-up protocols for patients undergoing primary focal unilateral nerve-sparing prostate cancer treatment.

The effect of argon gas pressure on ice ball size and rate of formation.

INTRODUCTION: Contemporary cryoablation technology utilizes the Joule-Thomson effect, defined as a change in temperature that results from expansion of a nonideal gas through an orifice or other restriction. We evaluated the effect of initial gas tank pressures on freezing dynamics in a single-probe model and in a multiprobe model using contemporary cryoablation technology. MATERIALS AND METHODS: Cryoablation trials were performed in a standardized system of transparent gelatin molds at 25°C. Two sets of trials were performed. The first trial evaluated temperature and ice ball size for a given tank pressure when a single needle was deployed. The second trial recorded ice ball temperatures for each probe when multiple probes were fired simultaneously. RESULTS: Trial 1: The rate of temperature change is directly related to the initial pressure of the gas being released, and the group with the highest starting pressures reached the lowest mean temperature and had the largest mean ice ball size (p < 0.01). Trail 2: Multiple-probe ablation did not affect the rate of temperature change or final temperature compared with firing a single probe (p > 0.7). CONCLUSIONS: In accordance with the Joule-Thomson effect, higher initial gas pressures used for cryoablation in a transparent gel model demonstrate statistically significant lower temperatures, faster decreases in temperature, and formation of larger ice balls than lower gas pressures do. With contemporary technology, multiple simultaneous cryoprobe deployment does not compromise individual probe efficacy. The use of higher initial tank pressures will theoretically help future cryoprobes be more effective, creating a greater volume of cell necrosis and a smaller indeterminate zone.

Long-term cancer-specific and overall survival for men followed more than 10 years after primary and salvage cryoablation of the prostate.

INTRODUCTION: Ten-year disease-specific survival for clinically localized prostate cancer after radiation is 93%, 88%, and 80% for low-, medium-, and high-risk groups, respectively. The objective of this study was to report long-term cancer survival outcomes for patients who had undergone prostate cryotherapy at our institution more than 10 years ago. To date, this is the longest reported follow-up after cryotherapy. MATERIALS AND METHODS: A retrospective patient chart review, conducted of an Institutional Review Board (IRB)- approved cryotherapy database, identified 76 men who had undergone prostate cryotherapy before January 1999. Pre-, intra-, and posttreatment data were collected. Primary study endpoints were overall mortality and prostate-cancer-specific death. Secondary endpoints were disease recurrence and clinical progression. RESULTS: Mean patient age was 69.2 (47.4-86.3) years; median preoperative prostate-specific antigen was 5.3 (0.2-208.0); mean Gleason score was 7. Forty of 76 (52.6%) were confirmed D'Amico high risk. Median follow-up was 10.1 (0.2-14.9) years; 25 patients underwent primary treatment; 51 postradiation. After 10 years of follow-up, 43 of 76 men (56.6%) were still alive; 33 men (43.4%) had died-10 (13.2%) from prostate cancer, 18 (22.4%) from noncancerous causes, and 5 (6.6%) unknown. CONCLUSIONS: The long-term results of prostate cryotherapy in our series indicate an 87% overall 10-year prostate-cancer-specific survival, despite early cryotherapy technology and the majority of patients being D'Amico high risk.