Aditya Bagrodia

Single-Incision, Umbilical Laparoscopic versus Conventional Laparoscopic Nephrectomy: A Comparison of Perioperative Outcomes and Short-Term Measures of Convalescence

BACKGROUND Recent reports have suggested that single-port or single-incision laparoscopic surgery (SILS) is technically feasible. OBJECTIVE To present a comparison between SILS and conventional laparoscopic nephrectomy with respect to perioperative outcomes and short-term measures of convalescence. DESIGN, SETTING, AND PARTICIPANTS This was a case-control study comparing 11 SILS nephrectomies (cases) and 22 conventional laparoscopic nephrectomies (controls) performed from September 2004 to April 2008. The control group was matched in a 2:1 ratio to SILS cases with respect to patient age, surgical indication, and tumor size. INTERVENTION A single surgeon performed all SILS nephrectomy cases using three adjacent 5-mm trocars inserted through a single 2.5-cm periumbilical incision. MEASUREMENTS Demographics, operative time, blood loss, perioperative complications, transfusion requirement, decrease in serum hemoglobin, analgesic requirement, length of stay, and final pathology were compared. RESULTS AND LIMITATIONS Mean patient age was 53 yr for both groups, with more females in the SILS cohort (82% vs 41%). Nephrectomy was performed for benign disease in 45% of the cases. Median tumor size was 5.5 cm for both groups, and all but one suspected malignancy was renal cell carcinoma on final pathology. There was no difference between SILS and conventional laparoscopy cases in median operative time (122 min vs 125 min, p=0.78), percent decrease from preoperative hemoglobin (14.1% vs 15.8%, p=0.52), analgesic use (8 morphine equivalents vs 15 morphine equivalents, p=0.69), length of stay (49 h vs. 53 h, p=0.44), or complication rate (0% for both). The SILS group did have a lower recorded median estimated blood loss (20 ml vs 100ml, p=0.001). This study is retrospective and is susceptible to all limitations and biases inherent in such a design. CONCLUSIONS SILS nephrectomy is feasible with perioperative outcomes and short-term measures of convalescence comparable to conventional laparoscopic nephrectomy. Although SILS may offer a subjective cosmetic advantage, prospective comparison is needed to more clearly define its role.

Radiation Exposure in the Acute and Short-Term Management of Urolithiasis at 2 Academic Centers

PURPOSE Diagnostic imaging has a central role in the evaluation and management of urolithiasis. A variety of modalities are available, each with benefits and limitations. Without careful consideration of imaging modalities in quantity and type patients may receive excessive doses of radiation during initial diagnostic and followup evaluations. Therefore, we determined the effective radiation dose associated with an acute stone episode and short-term followup. MATERIALS AND METHODS A multicenter retrospective study of all patients who presented with an acute stone episode was performed. The analysis included all imaging studies related to stone disease performed within 1 year of the acute event. Using accepted effective radiation dose standards for each of these examinations, the total radiation dose administered was calculated and compared by patient characteristics including stone location, stone number and intervention strategy. The primary outcome assessed was a total radiation dose greater than 50 mSv, the recommended yearly dose limit for occupational exposure by the International Commission on Radiological Protection. RESULTS We identified 108 patients who presented to our respective institutions with a primary acute stone episode between 2000 and 2006. The mean age in our cohort was 48.6 years and 50% of the patients were men. Patients underwent an average of 4 radiographic examinations during the 1-year period. Studies performed included a mean of 1.2 plain abdominal films of the kidneys, ureters and bladder (range 0 to 7), 1.7 abdominopelvic computerized tomograms (range 0 to 6) and 1 excretory urogram (range 0 to 3) during the first year of followup. The median total effective radiation dose per patient was 29.7 mSv (IQR 24.2, 45.1). There were 22 (20%) patients who received greater than 50 mSv. Analysis of stone location, number of stones, stone composition, patient age, sex and surgical intervention indicated no statistically significant difference in the probability of receiving a total radiation dose greater than 50 mSv. CONCLUSIONS A fifth of patients receive potentially significant radiation doses in the short-term followup of an acute stone event. Radiographic imaging remains an integral part of the diagnosis and management of symptomatic urolithiasis. While debate exists regarding the threshold level for radiation induced fatal malignancies, urologists must be cognizant of the radiation exposure to patients, and seek alternative imaging strategies to minimize radiation dose during acute and long-term stone management.

NATURAL HISTORY OF RESIDUAL FRAGMENTS FOLLOWING PERCUTANEOUS NEPHROSTOLITHOTOMY

PURPOSE We reviewed the natural history of residual fragments after percutaneous nephrostolithotomy. MATERIALS AND METHODS From April 1999 to January 2007 a total of 728 patients underwent percutaneous nephrostolithotomy at our medical center including 527 with a minimum documented radiographic followup of 6 months. Of these patients 42 (8%) with residual fragments on postoperative computerized tomography were observed rather than subjected to second look flexible nephroscopy. Computerized tomography was reviewed to define location, size and number of residual fragments. The primary study end point was a stone related event defined as growth of a residual fragment, or need for emergency room visit, hospitalization or additional intervention attributable to the residual fragment. Univariate and multivariate analyses were performed to determine predictors of a stone related event. RESULTS The median residual fragment size was 2 mm (range, 1 to 12). There were 18 patients (43%) who experienced a stone related event at a median of 32 months after percutaneous nephrostolithotomy (range 4 to 95). On univariate analysis residual fragment location in the renal pelvis or ureter (p = 0.02), maximum residual fragment size larger than 2 mm (p = 0.03) and cumulative residual fragment size (p = 0.03) predicted a stone related event. On multivariate analysis only maximum residual fragment size larger than 2 mm (HR 3.9, p = 0.01) and location in the renal pelvis or ureter (HR 4.4, p = 0.01) independently predicted a stone event. CONCLUSIONS The size and location of post-percutaneous nephrostolithotomy residual fragments correlate with stone related events. Larger fragments are more likely to require secondary surgical intervention. Second look flexible nephroscopy may be of benefit in patients with residual fragments larger than 2 mm or in those with fragments located in the renal pelvis or ureter.

Perioperative Outcomes in Patients Undergoing Conventional Laparoscopic Versus Laparoendoscopic Single-site Pyeloplasty

OBJECTIVES To compare the outcomes of laparoendoscopic single-site (LESS) surgery with conventional laparoscopic pyeloplasty (CLP) before LESS can be widely accepted. LESS surgery is a novel technique for performing laparoscopic pyeloplasty through a single incision. METHODS Fourteen patients undergoing less pyeloplasty were matched 2:1 with regard to age and side of surgery to a previous cohort of 28 patients who underwent CLP. All patients underwent surgery for symptomatic ureteropelvic junction obstruction and/or delayed urinary excretion based on functional imaging. Intracorporeal suturing was aided through a 5-mm instrument placed in the eventual drain site. RESULTS No difference was observed between the LESS and CLP cohorts in regard to preoperative characteristics. Postoperatively, no difference was noted between LESS and CLP cases in regard to length of stay (77 vs 74 hours; P = .69), morphine equivalents required (34 vs 38; P = .93), minor postoperative complications (14.3% vs 14.3%; P = 1.0), or major postoperative complications (21.4% vs 10%; P = .18). Median operative times (207 vs 237.5 minutes; P <.001) and median estimated blood loss (30 vs 72.5 mL; P = .002) were lower in patients undergoing LESS. Detailed follow-up imaging revealed a success rate of 96% for CLP at 14.6 months (86% follow-up) and 100% for LESS at 6.8 months (71% follow-up). CONCLUSIONS Although LESS pyeloplasty is feasible, all measured perioperative outcomes are similar to CLP. Further studies are needed to better define the appropriate role of LESS surgery in urology.

Comparison of rates and risk factors for developing chronic renal insufficiency, proteinuria and metabolic acidosis after radical or partial nephrectomy

To investigate the incidence of and risk factors for developing chronic renal insufficiency (CRI), proteinuria and metabolic acidosis (MA) in patients treated with radical nephrectomy (RN) or nephron‐sparing surgery (NSS).

Does the presence of hydronephrosis on preoperative axial CT imaging predict worse outcomes for patients undergoing nephroureterectomy for upper-tract urothelial carcinoma?

OBJECTIVES Hydronephrosis at the time of diagnosis of bladder cancer is associated with advanced disease and is a predictor of poorer outcomes. There is, however, limited information addressing whether a similar relationship exists for upper-tract urothelial carcinoma (UTUC). We investigate the prognostic impact of hydronephrosis on preoperative axial imaging on clinical outcomes after radical nephroureterectomy. MATERIALS AND METHODS The records for 106 patients with UTUC who underwent radical nephroureterectomy at 2 medical centers were reviewed. Preoperative computed tomography (CT) images were evaluated for ipsilateral hydronephrosis by radiologists blinded to clinical outcomes. Association of hydronephrosis with pathologic features and oncologic outcomes after surgery was assessed. RESULTS Sixty-seven men and 39 women with a median age of 69 years (range, 36 to 90) were evaluated. One-third of these patients had muscle invasive disease or greater (≥T2), 44% had high grade tumors, and 3% had lymph node (LN) metastases. At a median follow-up of 47 months (range, 1 to 164), 43% of patients experienced disease recurrence, 18% developed metastasis, and 12% died of their cancer. Thirty-nine patients (37%) had hydronephrosis on preoperative axial imaging; 35% of these patients had ureteral tumors, and 27% had multifocal disease. The presence of hydronephrosis was associated with advanced pathologic stage (P = 0.03) and disease in the ureter (vs. renal pelvis) (P = 0.007). Hydronephrosis was a predictor of non-organ confined disease on final pathology (hazard ratio [HR] 3.7, P = 0.01). On preoperative multivariable analysis controlling for age, gender, tumor location, ureteroscopic biopsy grade, and urinary cytology, hydronephrosis was independently associated with cancer metastasis (HR 8.2, P = 0.02) and cancer-specific death (HR 12.1, P = 0.03). CONCLUSIONS Preoperative hydronephrosis on axial imaging is associated with features of aggressive disease and predicts advanced pathologic stage for UTUC. Hydronephrosis can be a valuable prognostic tool for preoperative planning and counseling regarding disease outcomes.

Complete transvaginal NOTES nephrectomy using magnetically anchored instrumentation.

BACKGROUND AND PURPOSE Evolution of minimally invasive techniques has prompted interest in natural orifice transluminal endoscopic surgery (NOTES). Challenges for NOTES include loss of instrument rigidity, reduction in working envelopes, and collision of instrumentation. Magnetic anchoring and guidance system (MAGS) is one surgical innovation developed at our institution whereby instruments that are deployed intra-abdominally are maneuvered by the use of an external magnet. We present our initial animal experience with complete transvaginal NOTES nephrectomy using MAGS technology. MATERIALS AND METHODS Transvaginal NOTES nephrectomy was performed in two female pigs through a vaginotomy, using a 40-cm dual-lumen rigid access port inserted into the peritoneal cavity. A MAGS camera and cauterizer were deployed through the port and manipulated across the peritoneal surface by way of magnetic coupling via an external magnet. A prototype 70-cm articulating laparoscopic grasper introduced through the vaginal access port facilitated dissection after deployment of the MAGS instruments. The renal artery and vein were stapled en-bloc using an extra-long articulating endovascular stapler. RESULTS NOTES nephrectomies were successfully completed in both pigs without complications using MAGS instrumentation. The MAGS camera provided a conventional umbilical perspective of the kidney; the cauterizer, transvaginal grasper, and stapler preserved triangulation while avoiding instrument collisions. Operative duration for the two cases was 155 and 125 minutes, and blood loss was minimal. CONCLUSIONS NOTES nephrectomy using MAGS instrumentation is feasible. We believe this approach improves shortcomings of previously reported NOTES nephrectomies in that triangulation, instrument fidelity, and visualization are preserved while hilar ligation is performed using a conventional stapler without need for additional transabdominal trocars.

Bladder Cancer Screening in a High Risk Asymptomatic Population Using a Point of Care Urine Based Protein Tumor Marker

PURPOSE We evaluated whether screening high risk asymptomatic individuals with a bladder tumor marker can lead to earlier detection and resultant down staging of bladder cancer. MATERIALS AND METHODS Subjects at high risk for bladder cancer based on age and smoking or occupational status were solicited from 2 well patient clinics from March 2006 to November 2007. NMP22 BladderChek testing was performed on voided urine samples. Those with positive test results underwent office cystoscopy and cytology testing. Participants were contacted for followup at 12 months after study enrollment to evaluate for unrecognized bladder cancer. RESULTS A total of 1,175 men and 327 women underwent BladderChek testing. Mean participant age was 62.5 years (range 46 to 92). Based on 10-year or greater smoking history 1,298 participants were enrolled while 513 were enrolled based on a greater than 15-year high risk occupation for bladder cancer. Positive BladderChek testing was observed in 85 (5.7%) participants and 69 agreed to undergo cystoscopy. Three types of lesions were diagnosed including multifocal, high grade Ta (1); Ta, low grade tumor (1) and marked atypia (1). Followup was available in 1,309 subjects. Mean followup was 12 months (range 0.9 to 25.5) and 2 of 1,309 participants had low grade noninvasive bladder cancer. Evaluation of patient records revealed that 73.4% of participants had urinalysis within 3 years before screening. CONCLUSIONS NMP22 BladderChek for screening an asymptomatic, high risk population can detect noninvasive cancers but the low prevalence of bladder cancer in this population did not permit assessment of intervention efficacy. Frequent use of urinalyses in high risk persons may attenuate future efforts to study the effects of bladder cancer screening tests.

Genomic Characterization of Upper Tract Urothelial Carcinoma

BACKGROUND Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences. OBJECTIVE To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity. DESIGN, SETTING, AND PARTICIPANTS Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102). RESULTS AND LIMITATIONS Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed. CONCLUSIONS High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma. PATIENT SUMMARY Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.

Prospective Evaluation of a Molecular Marker Panel for Prediction of Recurrence and Cancer-specific Survival After Radical Cystectomy

BACKGROUND Retrospective studies demonstrated that cell cycle-related and proliferation biomarkers add information to standard pathologic tumor features after radical cystectomy (RC). There are no prospective studies validating the clinical utility of markers in bladder cancer. OBJECTIVE To prospectively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder (UCB) who were likely to experience disease recurrence or mortality. DESIGN, SETTING, AND PARTICIPANTS Between January 2007 and January 2012, every patient with high-grade bladder cancer, including 216 patients treated with RC and lymphadenectomy, underwent immunohistochemical staining for tumor protein p53 (Tp53); cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A); cyclin-dependent kinase inhibitor 1B (p27, Kip1); antigen identified by monoclonal antibody Ki-67 (MKI67); and cyclin E1. INTERVENTION Every patient underwent RC and lymphadenectomy, and marker staining. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality (CSM). RESULTS AND LIMITATIONS Pathologic stage among the study population was pT0 (5%), pT1 (35%), pT2 (19%), pT3 (29%), and pT4 (13%); lymphovascular invasion (LVI) was seen in 34%. The median number of removed lymph nodes was 23, and 60 patients had lymph node involvement (LNI). Median follow-up was 20 mo. Expression of p53, p21, p27, cyclin E1, and Ki-67 were altered in 54%, 26%, 46%, 15%, and 75% patients, respectively. In univariable analyses, pT stage, LNI, LVI, perioperative chemotherapy (CTx), margin status, and number of altered biomarkers predicted disease recurrence. In a multivariable model adjusting for pathologic stage, margins, LNI, and adjuvant CTx, only LVI and number of altered biomarkers were independent predictors of recurrence and CSM. The concordance index of a baseline model predicting CSM (including pathologic stage, margins, LVI, LNI, and adjuvant CTx) was 80% and improved to 83% with addition of the number of altered markers. CONCLUSIONS Molecular markers improve the prediction of recurrence and CSM after RC. They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy.