Mohit Gupta

Clinical Practice Guidelines on Prostate Cancer: A Critical Appraisal

PURPOSE Clinical practice guidelines are increasingly being used by leading organizations to promote high quality evidence-based patient care. However, the methodological quality of clinical practice guidelines developed by different organizations varies considerably. We assessed published clinical practice guidelines on the treatment of localized prostate cancer to evaluate the rigor, applicability and transparency of their recommendations. MATERIALS AND METHODS We searched for English based clinical practice guidelines on treatment of localized prostate cancer from leading organizations in the 15-year period from 1999 to 2014. Clinical practice guidelines limited to early detection, screening, staging and/or diagnosis of prostate cancer were excluded from analysis. Four independent reviewers used the validated AGREE II instrument to assess the quality of clinical practice guidelines in 6 domains, including 1) scope and purpose, 2) stakeholder involvement, 3) rigor of development, 4) clarity of presentation, 5) applicability and 6) editorial independence. RESULTS A total of 13 clinical practice guidelines met inclusion criteria. Overall the highest median scores were in the AGREE II domains of clarity of presentation, editorial independence, and scope and purpose. The lowest median score was for applicability (28.1%). Although the median score of editorial independence was high (85.4%), variability was also substantial (IQR 12.5-100). NICE and AUA clinical practice guidelines consistently scored well in most domains. CONCLUSIONS Clinical practice guidelines from different organizations on treatment of localized prostate cancer are of variable quality and fall short of current standards in certain areas, especially in applicability and stakeholder involvement. Improvements in these key domains can enhance the impact and implementation of clinical practice guidelines.

Intraoperative optical imaging and tissue interrogation during urologic surgery.

Purpose of review To review optical imaging technologies in urologic surgery aimed to facilitate intraoperative imaging and tissue interrogation. Recent findings Emerging new optical imaging technologies can be integrated in the operating room environment during minimally invasive and open surgery. These technologies include macroscopic fluorescence imaging that provides contrast enhancement between normal and diseased tissue and microscopic imaging that provides tissue characterization. Summary Optical imaging technologies that have reached the clinical arena in urologic surgery were reviewed, including photodynamic diagnosis, near infrared fluorescence imaging, optical coherence tomography, and confocal laser endomicroscopy.

Current and Evolving Uses of Optical Coherence Tomography in the Genitourinary Tract

Optical coherence tomography is an emerging imaging modality that provides high-resolution, real-time, cross-sectional visualization of urologic tissue with promising results. Early studies have demonstrated detailed, accurate histologic information of tissues sampled. Optical coherence tomography (OCT) has also been applied in evaluating malignancy of the bladder, prostate, and kidney. In the bladder, it can assist in the identification, biopsy, and intraoperative resection of lesions suspicious for bladder cancer. Intraoperative use of OCT during radical prostatectomy can improve visualization of the neurovascular bundle and surgical margins. Several small, ex vivo studies have also shown promising results in the ability of OCT to demonstrate histopathologic alterations to renal morphology such as in renal ischemia and malignancy. In men with non-obstructive azoospermia, OCT has also been used in improving sperm retrieval rates by assisting in the identification of tubules with isolated foci of spermatogenesis. Common limitations of OCT include limited depth of penetration and limited number of current clinical studies.

Delayed Intervention of Small Renal Masses on Active Surveillance

Although surgical excision is the standard of therapy for small renal masses (SRMs), there is a growing recognition of active surveillance as an option in select patients who are poor surgical candidates or who have shorter life expectancy. A number of patients on expectant management, however, subsequently advance to definitive therapy. In this study, we systematically reviewed the literature and performed a pooled analysis of active surveillance series to evaluate the rate and indications for definitive treatment after initiating a period of active surveillance. Fourteen clinical series (1245 patients; 1364 lesions) met our selection criteria. Mean lesion size at presentation was 2.30 ± 0.40 cm with a mean follow-up of 33.6 ± 16.9 months. Collectively, 34.0% of patients underwent delayed intervention, which ranged in individual series from 3.6% to 70.3%. Of patients undergoing delayed intervention, the average time on active surveillance prior to definitive treatment was 27.8 ± 10.6 months. A pooled analysis revealed that 41.0% of patients underwent therapy secondary to tumor growth rate and 51.9% secondary to patient or physician preference in the absence of clinical progression. Overall, 1.1% of all patients progressed to metastatic disease during the average follow-up period. Thus, active surveillance may be an appropriate option for carefully selected patients with SRMs. However, delayed treatment is pursued in a significant percentage of patients within 3 years. Prospective registries and clinical trials with standardized indications for delayed intervention are needed to establish true rates of disease progressions and recommendations for delayed intervention.

Optical Coherence Tomography for Prostate Cancer and Beyond

Since it was first used to evaluate human genitourinary tissue in 1997, OCT has emerged as a promising modality to provide real-time, high-resolution imaging of urologic organs. In the bladder, it has demonstrated a high sensitivity in identifying regions of the bladder suspicious for CIS and between invasive and noninvasive malignancy; it has been studied as an “optical biopsy” both during the initial cystoscopic diagnosis and intraoperatively in bladder-preserving surgery. Several small, ex vivo studies have shown promising results in the ability of OCT to demonstrate histopathologic alterations to renal morphology such as in renal ischemia and malignancy. It may also in the future improve sperm retrieval rates by better identifying tubules with isolated foci of spermatogenesis in these men with nonobstructive azoospermia. Finally, multiple studies have begun to demonstrate OCT’s ability to differentiate between the periprostatic anatomy and aid in the visualization of the neurovascular bundle and surgical margins. Despite the promising results of these initial studies, several limitations remain. In almost all studies, depth of penetration was recognized as a common limiting factor. At a maximum of 2 mm depth, OCT cannot provide imaging of deep tissue. In bladder cancer, for example, OCT cannot always provide sufficient imaging to judge the invasion depth of a tumor if the diameter of the tumor is already greater than 2 mm. In addition, most OCT studies have taken place in ex vivo. Larger clinical, in vivo trials are required to determine its ability to provide information to guide clinical decisions and if its use positively affects outcomes. Theoretically, future improvements of OCT delivery could allow for such technology to be placed at the end of robotic and laparoscopic instruments, thus providing “smart instruments” that could provide immediate and real-time assessment of tissue structure and architecture.

Complications of Robot-Assisted Radical Prostatectomy

Robotic surgery represents a shift in the surgical paradigm and is consequently associated with a unique set of challenges and complications in comparison to open or conventional laparoscopic surgery. For the first time, the surgeon is not directly at the bedside but is rather directing an intermediary machine and a separate bedside team to perform the operation. This, in addition to the lack of tactile feedback, the greater reliance on visual anatomic clues when performing robotic surgery, and the inherent risk of malfunction or mechanical failure of robotic components may all contribute to complications noted during robot-assisted radical prostatectomy (RARP). In this chapter, we outline the risks and incidence of the more common complications associated with RARP and present methods to manage them.

Dominant Role of Entropy in Stabilizing Sugar Isomerization Transition States within Hydrophobic Zeolite Pores

Lewis acid sites in zeolites catalyze aqueous-phase sugar isomerization at higher turnover rates when confined within hydrophobic rather than within hydrophilic micropores; however, relative contributions of competitive water adsorption at active sites and preferential stabilization of isomerization transition states have remained unclear. Here, we employ a suite of experimental and theoretical techniques to elucidate the effects of coadsorbed water on glucose isomerization reaction coordinate free energy landscapes. Transmission IR spectra provide evidence that water forms extended hydrogen-bonding networks within hydrophilic but not hydrophobic micropores of Beta zeolites. Aqueous-phase glucose isomerization turnover rates measured on Ti-Beta zeolites transition from first-order to zero-order dependence on glucose thermodynamic activity, as Lewis acidic Ti sites transition from water-covered to glucose-covered, consistent with intermediates identified from modulation excitation spectroscopy during in situ attenuated total reflectance IR experiments. First-order and zero-order isomerization rate constants are systematically higher (by 3-12×, 368-383 K) when Ti sites are confined within hydrophobic micropores. Apparent activation enthalpies and entropies reveal that glucose and water competitive adsorption at Ti sites depend weakly on confining environment polarity, while Gibbs free energies of hydride-shift isomerization transition states are lower when confined within hydrophobic micropores. DFT calculations suggest that interactions between intraporous water and isomerization transition states increase effective transition state sizes through second-shell solvation spheres, reducing primary solvation sphere flexibility. These findings clarify the effects of hydrophobic pockets on the stability of coadsorbed water and isomerization transition states and suggest design strategies that modify micropore polarity to influence turnover rates in liquid water.

The Effect of Continued Low Dose Aspirin Therapy in Patients Undergoing Percutaneous Nephrolithotomy

Purpose Aspirin is often stopped prior to percutaneous nephrolithotomy due to concern about the surgical bleeding risk. There is evidence that discontinuing aspirin perioperatively increases thromboembolic events and continuing it may be safe. We assessed the effect of continuing low dose aspirin through percutaneous nephrolithotomy and its effect on surgical and safety outcomes. Materials and Methods We retrospectively reviewed the records of 285 consecutive percutaneous nephrolithotomies performed between 2012 and 2015 at our institution. We compared outcomes and complications in patients who continued 81 mg aspirin daily to those in patients not receiving aspirin. Results A total of 67 patients (24.5%) were maintained on low dose aspirin and 207 (75.5%) were not on aspirin. The aspirin group was older (66 vs 52 years), included more tobacco users (58.2% vs 31.4%) and had a higher ASA® (American Society of Anesthesiologists®) score (2.9 vs 2.5, all p <0.001). There was no difference in mean S.T.O.N.E. (size, topography [stone location], obstruction, number of stones and evaluation of HU) score (7.6 vs 7.7, p = 0.71) or blood loss (44 vs 54 ml, p = 0.151). There was no difference in residual stone fragment size, including 0 to 2 mm in 65.3% vs 61.4% of aspirin vs no aspirin cases, 3 to 4 mm in 19.4% vs 16.2% and greater than 4 mm in 15.3% vs 22.4% (p = 0.407). Length of stay and the change in hemoglobin, hematocrit and creatinine were similar. There was no difference in the readmission rate (14.9% vs 12.6%, p = 0.618) or the total complication rate (34.4% vs 26.6%, p = 0.221). There was also no difference in the number of major complications (10.4% vs 5.8%, p = 0.193), bleeding complications (3.0% vs 2.9%, p = 0.971) and the transfusion rate (1.5% vs 1.0%, p = 0.57). Conclusions Percutaneous nephrolithotomy appears effective and safe in patients who continue low dose aspirin perioperatively.

MP92-01 SAFETY AND EFFICACY OF POST-OPERATIVE EXTENDED-DURATION VENOUS THROMBOEMBOLISM PROPHYLAXIS IN HIGH-RISK UROLOGIC ONCOLOGY PATIENTS

INTRODUCTION AND OBJECTIVES: Patients undergoing major urologic oncology surgery are at risk for post-operative venous thromboembolic events (VTE). The development of VTE following surgery often presents clinically after discharge and is associated with potentially significant morbidity and mortality. At present there is little published data on the safety and efficacy of extended duration venous thromboembolism prophylaxis (EDVTP) beyond the time of hospital discharge in urologic oncology patients. In this study, we evaluate the use of EDVTP for post-operative high-risk urologic oncology patients. METHODS: All patients undergoing major urologic oncology surgery by a single surgeon at our institution from April 2015 to present were evaluated for their risk for VTE using the Caprini risk assessment model. Patients considered high-risk (Caprini score 5) were discharged on post-operative EDVTP according to 2012 ACCP guidelines. 28 days of postoperative subcutaneous enoxaparin was considered the standard of care in eligible patients. These patients were prospectively monitored for the development of clinically symptomatic VTE within 30 days postoperatively and for adverse effects of EDVTP. RESULTS: 150 patients who underwent major urologic oncology surgery were considered to be at high VTE risk based on Caprini score of 5. Average patient age was 63.3 years and 68% of the patients were male. Surgical procedures performed included 39% radical cystectomy, 29% nephrectomy, 16% partial nephrectomy and 16% other. Average Caprini score was 7. Of these, 75% were candidates to receive a 28 day course of enoxaparin EDVTP. The most common reasons for the 25% of patients not receiving standard enoxaparin EDVTP included renal insufficiency (31%), atrial fibrillation requiring oral anticoagulation (26%), and previously diagnosed VTE requiring therapeutic anticoagulation (16%). Adherence to guidelines was not associated with any VTE prophylaxis complications. There were also no noted complications from the use of enoxaparin. The rate of observed 30-day symptomatic VTE in this population was 0%, with an anticipated rate of >5% based upon Caprini score. CONCLUSIONS: Post-operative use of EDVTP appears to be a safe and effective way to decrease the risk of VTE in high-risk urologic oncology patients. Additional data from larger registries is needed to evaluate and confirm the benefit gained and need for use of EDVTP in this patient population.

PD21-11 PCNL IN GERIATRIC PATIENTS: AN EVALUATION OF OUTCOMES, COMPLICATIONS AND DISCHARGE NEEDS

INTRODUCTION AND OBJECTIVES: Growing numbers of geriatric patients present for definitive management of kidney stones. Geriatric patients with large stones may be candidates for percutaneous nephrostolithotomy (PCNL), however their care-related needs may differ from younger patients. We reviewed our PCNL experience in geriatric patients to better define surgical outcomes, complications, and discharge needs. METHODS: We retrospectively analyzed patients undergoing PCNL from 2012-2015 in our institution. Preoperative characteristics, surgical outcomes, complications, and discharge needs were compared between two groups: geriatric patients (aged 65 years) and nongeriatric patients (<65years). Statistical analysis was performed with students t-test and chi-squared test. RESULTS: We analyzed 287 consecutive patients: 89(31%) patients 65 years; 198(69%) patients <65 years (mean age 72 vs 48 years, p<0.001). The results can be seen in Table 1. Geriatric patients were more likely Caucasian (91% vs 73.7%, p1⁄40.001), had fewer positive preoperative urine cultures (27% vs 41.6%, p1⁄40.017), and had higher American Society of Anesthesiologist scores (mean 2.83 vs 2.55, p<0.001). OR time (mean 159 vs 185 minutes, p1⁄40.003) and estimated blood loss (41 vs 56 mL, p1⁄40.014) were less in the geriatric group. The residual stone fragment size was less after one procedure (0-2 mm: 72.9% vs 58.5%; 3-4 mm: 15.6% vs 17.5%; >4 mm: 11.5% vs 24%, p1⁄40.024) in the geriatric group. There were no differences in 30 day readmissions (12.4% vs 12.6%, p1⁄40.95), total complications (30.3% vs 27.3%, p1⁄40.594) or major complications (9.0% vs 5.6% Clavien III p1⁄40.279) between the geriatric and non-geriatric groups respectively. Length of stay (3.1 vs 3.2 days, p1⁄40.852) was similar between the groups, however the geriatric group was more often discharged with services to assist with nephrostomy tubes or wound dressings (21.3% vs 9.1%, p1⁄40.016). CONCLUSIONS: PCNL is an acceptable surgical option in appropriately selected geriatric patients. These patients require more home nursing care, but otherwise do well compared to younger patients. This information may be helpful for both patient counseling and discharge planning in the geriatric stone population. Source of Funding: None