Gregory W. Hruby

Dysregulation of Circulating MicroRNAs and Prediction of Aggressive Prostate Cancer

It is becoming increasingly evident that microRNAs (miRNAs) are associated with the development and progression of prostate cancer (PCa).

Tissue Response to Surgical Energy Devices

OBJECTIVES There is little data available on the effects of energy-based surgical devices (ESD) on tissues other than arteries and veins. As such, we quantified the lateral thermal damage associated with contemporary ESD: the Harmonic ACE, a prototype bipolar device known as the Gyrus Trisector, the Harmonic LCS-C5, and the LigaSure V. METHODS We divided 24 domestic pigs into 4 groups, 1 group for each ESD tested. Segments of bladder, stomach, small bowel, colon, ureter, peritoneum, arteries, and veins were exposed to each ESD. The tissues were stained with hematoxylin and eosin and evaluated by an experienced pathologist to quantitate the lateral energy spread associated with each device. We measured blade temperatures of each device using the IR-Flex thermal camera. RESULTS The Trisector developed the lowest mean blade temperature (97.84 degrees F), whereas the LigaSures was the second lowest (103.14 degrees F). The ACE and LCS-C5 created the highest blade temperatures, measuring 220.5 degrees F and 205.6 degrees F, respectively. The Trisectors mean full thickness and superficial lateral energy damage were 6.3 mm and 7.0 mm, respectively, whereas the Ligasures was 4.5 mm and 5.9 mm, respectively. For the ACE, however, mean full thickness and superficial energy spread were 2.4 mm and 2.8 mm, respectively, whereas the LCS-C5s were 3.1 mm and 4.3 mm, respectively. CONCLUSIONS The Harmonic ACE and LCS-C5 produced the least thermal damage in the tissues tested. ESD-associated tissue energy damage is not directly related to blade temperature, but is likely the result of several factors including blade temperature, transection time, tissue properties, and the vascularity of each transected tissue.

First Prize (Tie): Laparoscopic Renal Cryoablation: Efficacy and Complications for Larger Renal Masses

BACKGROUND AND PURPOSE In expanding our indications for cryoablation of renal cortical neoplasms, there was an increased morbidity with laparoscopic cryoablation. As such, we evaluated our single institution experience with laparoscopic renal cryoablation for complications and oncologic effectiveness as a function of tumor size. MATERIALS AND METHODS We retrospectively evaluated our prospectively established urologic oncology database and identified 44 laparoscopic cryoablation procedures performed for the management of 51 renal masses. Measured parameters included patient age, tumor size and location, estimated blood loss, complications, and recurrences. Patients were stratified into two groups. In group 1, the patients presented with a maximum tumor diameter less than 3.0 cm. Group 2 patients had a maximum tumor diameter of 3.0 cm or larger. RESULTS Group 1 included 30 tumors in 23 patients, and group 2 had 21 tumors in 21 patients. The mean tumor size for groups 1 and 2 were 1.8 cm (range 0.7 to 2.8 cm) and 4.0 cm (range 3.0 to 7.5 cm), respectively (P < 0.0001). The average patient age for group 1 was 70.2 and group 2 was 77.6 years (P = 0.04). The mean American Society of Anesthesiologists score was 1.8 and 2.1 for groups 1 and 2, respectively (P = 0.06). There were no complications in group 1. Group 2 had 13 (62%) complications, including two mortalities. The most common complication was blood transfusions at 38%. With a mean follow-up of 9 months, there were no recurrences in group 1. With a mean follow-up of 11 months, there was a single (4.8%) recurrence in group 2. Biopsy histopathology revealed renal cell carcinoma variants in 46.7% in group 1 and 66.7% in group 2, respectively (P = 0.079). CONCLUSION Renal cryoablation of renal cortical neoplasms smaller than 3.0 cm is effective and safe. Our initial experience, however, demonstrates that cryoablation of larger renal masses may be associated with increased morbidity.

Relative efficacy of perioperative gemcitabine and cisplatin versus methotrexate, vinblastine, adriamycin, and cisplatin in the management of locally advanced urothelial carcinoma of the bladder.

OBJECTIVE To compare the outcomes of patients treated in the perioperative setting with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) versus gemcitabine and cisplatin (GC). Systemic cisplatin-based chemotherapy regimens are the mainstay of treatment for patients with advanced bladder cancer. GC has often been used interchangeably with MVAC in neoadjuvant or adjuvant settings for patients with locally advanced (cT2N0M0-cT4N2M0) bladder cancer without adequate evidence. METHODS A total of 114 patients treated with systemic chemotherapy for Stage T2-T4N0-N2M0 urothelial cell carcinoma of the bladder were included in the present study. The survival times were estimated and compared using the Kaplan-Meier method and log-rank test, respectively. Univariate and multivariate Cox proportional hazards models were used to determine the statistical significance. RESULTS Of the 114 patients included in the present study, 37 (32%) were treated with GC and 77 (68%) with MVAC. In the neoadjuvant group, no difference was found between the 2 chemotherapeutic regimens in terms of the pathologic complete response rate at either cystectomy or during cystoscopy (14 [31%] of 45 MVAC patients vs 4 [25%] of 16 GC patients; P=.645). On multivariate analysis, the choice of regimen was not an independent predictor of cancer-specific death (hazard ratio 1.3, 95% confidence interval 0.67-2.57; P=.421) or overall survival (hazard ratio 1.3, 95% confidence interval 0.76-2.24; P=.330). CONCLUSION Despite the lack of data on the relative efficacy of GC versus MVAC in the neoadjuvant and adjuvant settings, these regimens have been used interchangeably. The present investigation did not find the choice of cisplatin-based regimen to be an independent predictor of survival. A trend was seen toward improved survival and a greater complete response rate in the MVAC group.

Prospective Randomized Comparison of a Combined Ultrasonic and Pneumatic Lithotrite with a Standard Ultrasonic Lithotrite for Percutaneous Nephrolithotomy

PURPOSE To compare the efficiency and cost effectiveness of a combined pneumatic and ultrasonic lithotrite (Lithoclast Ultra) and a standard ultrasonic lithotrite, (LUS-1) during percutaneous nephrolithotomy. MATERIALS AND METHODS In a prospective randomized trial, 30 patients undergoing percutaneous nephrolithotomy (PCNL) were randomized to PCNL with either the combined pneumatic and ultrasonic lithotrite (PUL) or a standard ultrasonic lithotrite (SUL). Patient demographics, stone composition, location, pre- and post-operative stone burden, fragmentation rates, and device failures were compared. RESULTS There were 13 patients in the PUL group and 17 patients in the SUL group. Stone burden and location were equal. Overall, 64% of the PUL group had hard stones (defined as stones that were either pure or a mixture of cystine [3], calcium oxalate monohydrate [CaOxMono; 2], and calcium phosphate [CaPO4; 2]), and four had soft stones (3 struvite and 1 uric acid [UA]). In the SUL group, there were eight hard stones (5 CaOxMono and 3 CaPO4), and six soft stones (4 calcium oxalate dihydrate [CaOxDi] and 2 UA) (P = 0.51). Stone composition data were unavailable for five patients. Fragmentation time for the PAL was 37 minutes versus 31.5 minutes for the SUL (P = 0.22). Stone retrieval and mean operative times were similar for both groups. There were a total of three (23.1%) device-related problems in the PUL group, and eight (47%) in the SUL group. There was one (7.7%) device malfunction in the PUL group due to probe fracture. There were two (11.7%) device failures in the SUL group; one failure required the device to be reset every 30 minutes, and the second was an electrical failure. Suction tubing obstruction occurred twice (15.3%) in the PUL group and 35.3% in the SU group (P = 0.35). The stone-free rates for the PUL and SUL were 46% and 66.7%, respectively (P = 0.26). CONCLUSION Although the PUL was more costly, stone ablation and clearance rates were similar for both the combined pneumatic and ultrasonic device and the standard ultrasonic device. When stratified with respect to stone composition, the PUL was more efficient for harder stones, and the SUL was more efficient for softer stones.

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 Gleasons 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.

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

Study Type – Diagnosis (exploratory cohort)

Risk factors associated with renal parenchymal fracture during laparoscopic cryoablation

To assess the risk factors for haemorrhage and renal fracture associated with renal cryoablation.

Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference?

Study Type – Aetiology (individual cohort)

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

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.