Mohamad E. Allaf

Laparoendoscopic Single-site Surgery in Urology: Worldwide Multi-institutional Analysis of 1076 Cases

BACKGROUND Laparoendoscopic single-site surgery (LESS) has gained popularity in urology over the last few years. OBJECTIVE To report a large multi-institutional worldwide series of LESS in urology. DESIGN, SETTING, AND PARTICIPANTS Consecutive cases of LESS done between August 2007 and November 2010 at 18 participating institutions were included in this retrospective analysis. INTERVENTION Each group performed a variety of LESS procedures according to its own protocols, entry criteria, and techniques. MEASUREMENTS Demographic data, main perioperative outcome parameters, and information related to the surgical technique were gathered and analyzed. Conversions to reduced-port laparoscopy, conventional laparoscopy, or open surgery were evaluated, as were intraoperative and postoperative complications. RESULTS AND LIMITATIONS Overall, 1076 patients were included in the analysis. The most common procedures were extirpative or ablative operations in the upper urinary tract. The da Vinci robot was used to operate on 143 patients (13%). A single-port technique was most commonly used and the umbilicus represented the most common access site. Overall, operative time was 160±93 min and estimated blood loss was 148±234 ml. Skin incision length at closure was 3.5±1.5 cm. Mean hospital stay was 3.6±2.7 d with a visual analog pain score at discharge of 1.5±1.4. An additional port was used in 23% of cases. The overall conversion rate was 20.8%; 15.8% of patients were converted to reduced-port laparoscopy, 4% to conventional laparoscopy/robotic surgery, and 1% to open surgery. The intraoperative complication rate was 3.3%. Postoperative complications, mostly low grade, were encountered in 9.5% of cases. CONCLUSIONS This study provides a global view of the evolution of LESS in the field of minimally invasive urologic surgery. A broad range of procedures have been effectively performed, primarily in the academic setting, within diverse health care systems around the world. Since LESS is performed by experienced laparoscopic surgeons, the risk of complications remains low when stringent patient-selection criteria are applied.

Trends in Renal Surgery: Robotic Technology is Associated with Increased Use of Partial Nephrectomy

PURPOSE Underuse of partial vs radical nephrectomy for renal tumors was noted in recent population based analyses. An explanation is the learning curve associated with laparoscopic partial nephrectomy. We analyzed state trends in renal surgery and their relationship to the introduction of robotic technology. MATERIALS AND METHODS We used the Maryland HSCRC (Health Services Cost Review Commission) database to identify patients who underwent radical or partial nephrectomy, or renal ablation from 2000 to 2011. Utilization trends, and associated patient and hospital factors were analyzed using multivariate logistic regression. ICD-9 robotic modifier codes were established in October 2008. RESULTS Of the 14,260 patients included in analysis 11,271 (79.0%), 2,622 (18.4%) and 367 (2.6%) underwent radical and partial nephrectomy, and renal ablation, respectively. Partial nephrectomy increased from 8.6% in 2000 to 27% in 2011. Open radical nephrectomy decreased by 33%, while minimally invasive radical nephrectomy increased by 15%. Robot-assisted laparoscopic partial nephrectomy increased from 2008 to 2011, attaining a 14% rate at university and 10% at nonuniversity hospitals (p = 0.03). It was associated with increased partial nephrectomy (OR 9.67, p <0.001). Younger age, male gender and low patient complexity predicted partial nephrectomy on overall analysis, while higher hospital volume and university status were predictors only in earlier years. CONCLUSIONS Partial nephrectomy use increased in Maryland from 2001 to 2011, which was facilitated by robotic technology. Associations with hospital factors decreased with time. These data suggest that robotic technology may enable surgeons across practice settings to more frequently perform nephron sparing surgery.

Computerized Tomography Guided Percutaneous Renal Cryoablation With the Patient Under Conscious Sedation: Initial Clinical Experience

PURPOSE We report on our initial clinical experience with CT guided percutaneous renal cryoablation. MATERIALS AND METHODS CT guided percutaneous renal cryoablation was performed on 27 tumors using conscious sedation in 20 patients. Eligible patients had tumors of 5 cm or less and were poor surgical candidates or otherwise warranted nephron sparing treatment. Tumors were classified as central or noncentral depending on their relationship to the renal sinus fat. During cryoablation intraoperative active ice ball formation was monitored with real-time CT imaging to ensure adequate tumor coverage. Postoperative followup imaging was obtained at regular intervals. RESULTS Our method appears technically feasible as of the 27 cryoablations performed, only 1 complication occurred requiring blood transfusion in a patient with a large, centrally located tumor. To date we have 16 tumors in 12 patients with imaging followup of 1 month or more (mean followup 5.9 months). Mean baseline tumor size in this group was 2.5 cm with 11 small (3 cm or less) and 5 large (more than 3 cm) tumors. Of the tumors 5 were centrally located and 11 were noncentrally located. Preliminary data suggest that of the 16 cryoablated tumors 15 showed no signs of enhancement on followup. CONCLUSIONS CT guided percutaneous renal cryoablation appears to be a feasible treatment option for small, noncentrally located renal tumors. While early results appear promising, longer followup is needed to more clearly define the role of this treatment method.

Robotic-assisted Versus Traditional Laparoscopic Partial Nephrectomy: Comparison of Outcomes and Evaluation of Learning Curve

OBJECTIVES To examine the transition to robot-assisted laparoscopic partial nephrectomy (RALPN) from pure laparoscopic partial nephrectomy (LPN) and investigate the learning curve (LC). RALPN has emerged as a minimally invasive alternative to nephron-sparing surgery. METHODS A total of 150 consecutive patients were identified who underwent LPN or RALPN in the initial experience of a single surgeon since 2006. The perioperative data were evaluated using appropriate comparative tests. The LC was investigated by examining the operative times, warm ischemia times (WITs), and estimated blood loss (EBL) in groups of 25 consecutive patients. To account for laparoscopic LC, the outcomes of patients who underwent surgery in 2009 or later were also compared. RESULTS Of the 150 patients, 102 and 48 underwent LPN and RALPN, respectively. The patient and tumor characteristics were similar. The mean operative time (193 vs 152 minutes, P < .001), WIT (18.0 vs 14.0, P < .001), and EBL (245 vs 122 mL, P = .001) favored RALPN. Improvements in the operative time (P = .01), WIT (P = .006), and EBL (P = .01) were noted as experience increased in the LPN cohort and was most pronounced after the first 25 LPN patients. Since 2009, 55 and 44 patients underwent LPN and RALPN, respectively. Although the absolute differences were less, the operative time (182 vs 150, P < .001), WIT (15.3 vs 13.3, P < .001), and EBL (206 vs 118, P = .005) favored RALPN. CONCLUSIONS RALPN appears to have shorter operative and ischemia times and less blood loss compared with LPN. After a LC of approximately 25 cases, the transition from LPN to RALPN can be undertaken without an additional LC and can be associated with immediate benefits.

TERT Promoter Mutations Occur Early in Urothelial Neoplasia and Are Biomarkers of Early Disease and Disease Recurrence in Urine

Activating mutations occur in the promoter of the telomerase reverse transcriptase (TERT) gene in 66% of muscle-invasive urothelial carcinomas. To explore their role in bladder cancer development and to assess their utility as urine markers for early detection, we sequenced the TERT promoter in 76 well-characterized papillary and flat noninvasive urothelial carcinomas, including 28 pTa low-grade transitional cell carcinomas (TCC), 31 pTa high-grade TCCs, and 17 pTis carcinoma in situ lesions. We also evaluated the sequence of the TERT promoter in a separate series of 14 early bladder neoplasms and matched follow-up urine samples to determine whether urine TERT status was an indicator of disease recurrence. A high rate of TERT promoter mutation was observed in both papillary and flat lesions, as well as in low- and high-grade noninvasive urothelial neoplasms (mean: 74%). In addition, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of the six patients that did not recur (P < 0.001). TERT promoter mutations occur in both papillary and flat lesions, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and seem to be strongly associated with bladder cancer recurrence. These provocative results suggest that TERT promoter mutations may offer a useful urinary biomarker for both early detection and monitoring of bladder neoplasia.

Five-year Analysis of a Multi-institutional Prospective Clinical Trial of Delayed Intervention and Surveillance for Small Renal Masses: The DISSRM Registry ☆

BACKGROUND A growing body of retrospective literature is emerging regarding active surveillance (AS) for patients with small renal masses (SRMs). There are limited prospective data evaluating the effectiveness of AS compared to primary intervention (PI). OBJECTIVE To determine the characteristics and clinical outcomes of patients who chose AS for management of their SRM. DESIGN, SETTING, AND PARTICIPANTS From 2009 to 2014, the multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 497 patients with solid renal masses ≤4.0cm who chose PI or AS. INTERVENTION AS versus PI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The registry was designed and powered as a noninferiority study based on historic recurrence rates for PI. Analyses were performed in an intention-to-treat manner. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). RESULTS AND LIMITATIONS Of the 497 patients enrolled, 274 (55%) chose PI and 223 (45%) chose AS, of whom 21 (9%) crossed over to delayed intervention. AS patients were older, had worse Eastern Cooperative Oncology Group scores, total comorbidities, and cardiovascular comorbidities, had smaller tumors, and more often had multiple and bilateral lesions. OS for PI and AS was 98% and 96% at 2 yr, and 92% and 75% at 5 yr, respectively (log rank, p=0.06). At 5 yr, CSS was 99% and 100% for PI and AS, respectively (p=0.3). AS was not predictive of OS or CSS in regression modeling with relatively short follow-up. CONCLUSIONS In a well-selected cohort with up to 5 yr of prospective follow-up, AS was not inferior to PI. PATIENT SUMMARY The current report is among the first prospective analyses of patients electing for active surveillance of a small renal mass. Discussion of active surveillance should become part of the standard discussion for management of small renal masses.

Positive Surgical Margins in Robot-Assisted Partial Nephrectomy: A Multi-Institutional Analysis of Oncologic Outcomes (Leave No Tumor Behind)

PURPOSE Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. MATERIALS AND METHODS Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. RESULTS A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p<0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test<0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. CONCLUSIONS Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management.

Perioperative Complications of Robot-assisted Partial Nephrectomy: Analysis of 886 Patients at 5 United States Centers

OBJECTIVE To review complications of robot-assisted partial nephrectomy (RAPN) at 5 centers, as classified by the Clavien system. MATERIALS AND METHODS A multi-institutional analysis of prospectively maintained databases assessed RAPN complications. From June 2007 to November 2011, 886 patients at 5 United States centers underwent RAPN. Patient demographics, perioperative outcomes, and complications data were collected. Complication severity was classified by Clavien grade. RESULTS Mean (standard deviation) data were patient age, 59.4 (11.4) years; age-adjusted Charlson Comorbidity Index, 3.0 (1.9); radiographic tumor size, 3.0 (1.6) cm; nephrometry score, 6.9 (2.0); and warm ischemia time, 18.8 (9.0) minutes. Median blood loss was 100 mL (interquartile range, 100-250 mL). Of the 886 patients, intraoperative complications occurred in 23 patients (2.6%) and 139 postoperative complications occurred in 115 patients (13.0%) for a total complication rate of 15.6%. Among the 139 postoperative complications, 43 (30.9%) were classified as Clavien 1, 64 (46.0%) were Clavien 2, 21 (15.1%) were Clavien 3, and 11 (7.9%) were Clavien 4. No complication-related deaths occurred. Intraoperative hemorrhage occurred in 9 patients (1.0%) and postoperative hemorrhage in 51 (5.8%). Forty-one patients (4.6%) required a perioperative blood transfusion, 10 (1.1%) required angioembolization, and 2 (0.2%) required surgical reexploration for postoperative hemorrhage. Urine leaks developed in 10 patients (1.1%): 3 (0.3%) required ureteral stenting, and 2 (0.2%) required percutaneous drainage. Acute postoperative renal insufficiency or renal failure developed in 7 patients (0.8%), 2 of whom required hemodialysis. The RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior descriptor and the location relative to polar lines) nephrometry scoring system accurately predicted RAPN complication rates. CONCLUSION Complication rates in this large multicenter series of RAPN appear to be acceptable and comparable with other nephron-sparing modalities. Most complications (77.0%) are Clavien 1 and 2 and can be managed conservatively.

Utilization of a TFE3 break-apart FISH assay in a renal tumor consultation service.

Xp11 translocation renal cell carcinomas (RCCs) are characterized by chromosome translocations involving the Xp11.2 breakpoint, resulting in gene fusions involving the TFE3 transcription factor. In archival material, the diagnosis can often be confirmed by TFE3 immunohistochemistry (IHC), but variable fixation (especially prevalent in consultation material) can lead to equivocal results. A TFE3 break-apart fluorescence in situ hybridization (FISH) assay has been developed to detect TFE3 gene rearrangements; however, the utility of this assay in a renal tumor consultation practice has not been examined. We reviewed 95 consecutive renal tumor consultation cases submitted to rule in or rule out Xp11 translocation RCC. Thirty-one cases were positive for TFE3 rearrangements by FISH. Patients ranged from 6 to 67 years of age (mean=30 y; median=28 y). Novel or distinctive morphologic features of these cases included extensive cystic change simulating multilocular cystic RCC (3 cases), sarcomatoid transformation (3 cases), oncocytic areas mimicking oncocytoma (1 case), trabecular architecture mimicking a carcinoid tumor (1 case), colonization of renal pelvic urothelium mimicking urothelial carcinoma in situ (1), and focal desmin and diffuse racemase immunoreactivity (1 case each). Twenty-six of the 31 TFE3 FISH-positive RCCs were unequivocally positive for TFE3 by IHC, but 4 were equivocal, and 1 was negative. Of the 64 cases that were negative by TFE3 FISH, 50 were negative by TFE3 IHC, and 14 were equivocal. Thirty-two of the 64 TFE3 FISH-negative cases could be classified into other accepted RCC subtypes: 23 as clear cell RCC, 5 as papillary RCC, 3 as clear cell papillary RCC, and 1 as chromophobe RCC. The other 32 cases remained unclassified, including 3 cathepsin K-positive RCC that closely resembled Xp11 translocation RCC. In conclusion, TFE3 FISH is highly useful in renal tumor consultation material, often resolving cases with equivocal TFE3 IHC results. Given the difficulty of optimizing TFE3 IHC, TFE3 FISH is for most laboratories the optimal test for establishing the diagnosis of Xp11 translocation RCC.

Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: a multi-institutional study

To compare the perioperative outcomes of robotic partial nephrectomy (RPN) with laparoscopic PN (LPN) performed for small renal masses (SRMs), in a large multi‐institutional series and to define a new composite outcome measure, termed ‘optimal outcome’ for the RPN group.