3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

Partial nephrectomy margin imaging using structured illumination microscopy.

Partial nephrectomy (PN) is the recommended procedure over radical nephrectomy (RN) for patients with renal masses less than 4 cm in diameter (Stage T1a). Patients with less than 4 cm renal masses can also be treated with PN, but have a higher risk for positive surgical margins (PSM). PSM, when present, are indicative of poor clinical outcomes. The current gold-standard histopathology method is not well-suited for the identification of PSM intraoperatively due to processing time and destructive nature. Here, video-rate structured illumination microscopy (VR-SIM) was investigated as a potential tool for PSM detection during PN. A clinical image atlas assembled from ex vivo renal biopsies provided diagnostically useful images of benign and malignant kidney, similar to permanent histopathology. VR-SIM was then used to image entire parenchymal margins of tumor resection covering up to >1800× more margin surface area than standard histology. Aided by the image atlas, the study pathologist correctly classified all parenchymal margins as negative for PSM with VR-SIM, compared to standard postoperative pathology. The ability to evaluate large surgical margins in a short time frame with VR-SIM may allow it to be used intraoperatively as a "safety net" for PSM detection, allowing more patients to undergo PN over RN.

Racial Disparities in Histology and Short-Term Renal Functional Outcomes Following Robotic Nephron-Sparing Surgery.

PURPOSE: To identify variations in renal function and histology between Caucasian Americans (CA) and African Americans (AA) undergoing robotic nephron-sparing surgery (NSS). METHODS: A retrospective chart review was performed on patients who underwent NSS. Multivariate analysis identified factors affecting postoperative estimated glomerular filtration rate (eGFR). Histology was re-reviewed by pathology to confirm papillary type. RESULTS: A total of 331 patients underwent NSS: CA (n = 212), AA (n = 105), Hispanic (n = 10), and other (n = 4). AA average age (60.1 years) was lower than CA (62.3 years) (P < .001), with a higher proportion of AA women (46%) than CA (37%) (P = .021). AA had a higher incidence of diabetes (58.2%) and hypertension (93.9%). Preoperative average eGFR was similar: 70.35 mL/min for AA versus 69.06 mL/min for CA. Average postoperative eGFR was 50.59 mL/min for AA and 57.85 mL/min for CA. Postoperative creatinine increased more in AA (0.44 mg/dL) versus CA (0.33 mg/dL) (P < .001) even when stratified by pathological stage. Clear cell renal cell carcinoma (RCC) was the most common histology with AA (45%) and CA (60%). A greater than 2-fold higher incidence of papillary RCC was observed in AA (31%) versus CA (13%). AA exhibited a greater proportion of high-grade or type 2 papillary RCC (40% and 30%) versus CA (25% and 13%). CONCLUSIONS: AA patients were treated at a younger age, with a larger proportion of women. Postoperatively, AA experienced a greater increase in serum creatinine. Final histology demonstrated greater papillary RCC incidence in AA and increased likelihood for type 2 papillary RCC, a more aggressive histology.

Gigapixel surface imaging of radical prostatectomy specimens for comprehensive detection of cancer-positive surgical margins using structured illumination microscopy.

Achieving cancer-free surgical margins in oncologic surgery is critical to reduce the need for additional adjuvant treatments and minimize tumor recurrence; however, there is a delicate balance between completeness of tumor removal and preservation of adjacent tissues critical for normal post-operative function. We sought to establish the feasibility of video-rate structured illumination microscopy (VR-SIM) of the intact removed tumor surface as a practical and non-destructive alternative to intra-operative frozen section pathology, using prostate cancer as an initial target. We present the first images of the intact human prostate surface obtained with pathologically-relevant contrast and subcellular detail, obtained in 24 radical prostatectomy specimens immediately after excision. We demonstrate that it is feasible to routinely image the full prostate circumference, generating gigapixel panorama images of the surface that are readily interpreted by pathologists. VR-SIM confirmed detection of positive surgical margins in 3 out of 4 prostates with pathology-confirmed adenocarcinoma at the circumferential surgical margin, and furthermore detected extensive residual cancer at the circumferential margin in a case post-operatively classified by histopathology as having negative surgical margins. Our results suggest that the increased surface coverage of VR-SIM could also provide added value for detection and characterization of positive surgical margins over traditional histopathology.

Electroencephalographic Monitoring of Brain Wave Activity During Laparoscopic Surgical Simulation to Measure Surgeon Concentration and Stress: Can the Student Become the Master?

PURPOSE: To measure gamma and alpha brain wave activity as a measurement of concentration and stress levels during surgical simulator performance of laparoscopic tasks to determine if expert surgeons have different brain activity patterns compared with intermediate and novice surgeons. MATERIALS AND METHODS: After obtaining Institutional Review Board approval, 1st and 2nd year medical students, urology residents (PGY2-PGY5), and attending urologists from one institution were recruited. Participants were stratified by level of experience and performed laparoscopic tasks on the EDGE laparoscopic simulator. Subjects were evaluated for concentration and stress levels using the electroencephalography (EEG) data extracted from the MUSE(™) headband. The MUSE software developer kit (SDK) allowed quantification of gamma and alpha waves during each task. An analysis of variance was used to compare concentration and stress levels between groups. RESULTS: A total of 19 participants were recruited for the study and stratified by surgical experience into novice, intermediate, and expert laparoscopy groups: 6 medical students, 9 urology residents, and 4 attending urologists, respectively. Concentration and stress were quantified by calculating the area under the curve of the gamma and alpha EEG wave tracings. Stress was significantly lower in the attending urologists compared with the residents and medical students during the laparoscopic suturing and trended toward significance in the peg transfer task (P = 0.0003, P = 0.069). Concentration was significantly higher in the expert group compared with the less experienced groups during both the peg and suture tasks (P = 0.036, P = 0.0039). CONCLUSIONS: EEG brain activity in more experienced surgeons reveals a significant increase in concentration levels with a decrease in stress during simulated laparoscopic tasks compared with novices. This information may correlate with increased proficiency as well as provide objective feedback of progress along the learning curve with the MUSE SDK.

Individualized Physical 3-dimensional Kidney Tumor Models Constructed From 3-dimensional Printers Result in Improved Trainee Anatomic Understanding.

OBJECTIVE: To evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy. METHODS: Proprietary software was used to import standard computed tomography (CT) cross-sectional imaging into 3D printers to create physical models of renal units with enhancing renal lesions in situ. Six different models were printed from a transparent plastic resin; the normal parenchyma was printed in a clear, translucent plastic, with a red hue delineating the suspicious renal lesion. Medical students, who had completed their first year of training, were given an overview and tasked with completion of RENAL nephrometry scores, separately using CT imaging and 3D models. Trainees were also asked to complete a questionnaire about their experience. Variability between trainees was assessed by intraclass correlation coefficients (ICCs), and kappa statistics were used to compare the trainee to experts. RESULTS: Overall trainee nephrometry score accuracy was significantly improved with the 3D model vs CT scan (P <.01). Furthermore, 3 of the 4 components of the nephrometry score (radius, nearness to collecting system, and location) showed significant improvement (P <.001) using the models. There was also more consistent agreement among trainees when using the 3D models compared with CT scans to assess the nephrometry score (intraclass correlation coefficient, 0.28 for CT scan vs 0.72 for 3D models). Qualitative evaluation with questionnaires filled out by the trainees further confirmed that the 3D models improved their ability to understand and conceptualize the renal mass. CONCLUSION: Physical 3D models using readily available printing techniques improve trainees' understanding and characterization of individual patients' enhancing renal lesions.

Stratification of Expert vs Novice Laparoscopists Using the Basic Laparoscopic Urologic Surgery (BLUS) Curriculum at a Single Institution.

PURPOSE: To assess determinants of performance applying the tasks of the Basic Laparoscopic Urologic Surgery (BLUS) skills curriculum administered at a single institution. METHODS: After obtaining institutional review board approval, fourth-year medical students, urology residents (postgraduate year 1-5), and staff attending surgeons from an academic institution were recruited. Participants were grouped by level of experience and evaluated on 4 different BLUS modules testing fundamental laparoscopic techniques from September 2012 to September 2013. Task completion time (TCT) and missed objectives were compared with previous laparoscopic experience, amount of endourological training, and scores obtained through the EDGE simulator. RESULTS: TCTs among the participants were slower and accrued greater errors in the novice group (n = 10) than in the intermediate-level (n = 9) and expert-level (n = 9) groups. Completion times on the peg transfer were 213.4, 128.1, and 108.7 seconds (p < 0.05); on the circle cutting were 182.4, 128.3, and 97.2 seconds (p < 0.05); on the clip application were 44.4, 43.2, and 38.1 seconds (p = 0.08); and on the suturing were 286.1, 177.3, and 123.6 seconds (p < 0.05) for novice, intermediate, and expert groups, respectively. When past laparoscopic numbers of participants were compared with TCTs, a positive correlation of R(2) = 0.39 was seen, signifying a relationship between number of laparoscopic cases and TCT outcomes. CONCLUSION: Performance on the EDGE simulator device during the BLUS modules significantly correlated with the amount of laparoscopic experience. Increase in the years of experience and number of laparoscopic cases led to faster and more accurate TCTs.

Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 µM from 24 to 96 h, respectively. At maximum dosage and time (15 µM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 µM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy.

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals ). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Active surveillance of prostate cancer in African American men.

Active surveillance (AS) is a treatment strategy for prostate cancer (PCa) whereby patients diagnosed with PCa undergo ongoing characterization of their disease with the intent of avoiding radical treatment. Previously, AS has been demonstrated to be a reasonable option for men with low-risk PCa, but existing cohorts largely consist of Caucasian Americans. Because African Americans have a greater incidence, more aggressive, and potentially more lethal PCa than Caucasian Americans, it is unclear if AS is appropriate for African Americans. We performed a review of the available literature on AS with a focus on African Americans.

Physical models of renal malignancies using standard cross-sectional imaging and 3-dimensional printers: a pilot study.

OBJECTIVE: To construct high-fidelity, patient customized, physical, 3-dimensional (3D) models of renal units with enhancing renal lesions identified on cross-sectional imaging, which may aid patients, trainees, and clinicians in their comprehension, characterization, localization, and extirpation of suspicious renal masses. METHODS: Specialized software was used to import patient's diagnostic computerized tomography cross-sectional imaging into 3D printers and create physical 3D models of renal units with enhancing in situ lesions. Patients and trainees had the opportunity to manipulate the individualized model before surgical resection. Sterolithography additive manufacturing, a technique in which an ultraviolet laser is used to cure a photosensitive resin in sequential horizontally oriented layers, was used to build the models (Medical Modeling Inc., Golden, CO). Normal renal parenchyma was printed with a clear translucent resin, and red translucent resin delineated suspicious lesions. Renal vasculature and the proximal collecting system were printed in some models. RESULTS: We constructed 5 physical models of renal units with suspected malignancies before surgery. All patients successfully underwent partial nephrectomy (4 robotic and 1 open). Average ischemia time was 21 minutes, nephrometry score was 6.8, and all margins were negative. Anecdotally, patients, their families, and trainees consistently stated that the models enhanced their comprehension of the renal tumor in relation to surrounding normal renal parenchyma and hilar structures and improved understanding of the goals of the surgery. CONCLUSION: Preoperative physical 3D models using available printing techniques can be constructed and may potentially influence both patients' and trainees' understanding of renal malignancies.

Nomogram to predict prostate cancer diagnosis on primary transrectal ultrasound-guided prostate biopsy in a contemporary series.

OBJECTIVE: Transrectal ultrasound-guided biopsy (TRUSB) remains the mainstay for prostate cancer (CaP) diagnosis. Numerous variables have shown associations with development of CaP. We present a nomogram that predicts the probability of detecting CaP on TRUSB. METHODS: After obtaining institutional review board approval, all patients undergoing primary TRUSB for CaP detection at a single center at our institution between 2/2000 and 9/2007 were reviewed. Patients undergoing repeat biopsies were excluded, and only the first biopsy was included in the analysis. Variables included age at biopsy, race, clinical stage, prostate specific antigen (PSA), number of cores removed, TRUS prostate volume (TRUSPV), body mass index, family history of CaP, and pathology results. S-PLUS 2000 statistical software was utilized with p < 0.05 considered significant. Cox proportional hazards regression models with restricted cubic splines were utilized to construct the nomogram. Validation utilized bootstrapping, and the concordance index was calculated based on these predictions. RESULTS: A total of 1,542 consecutive patients underwent primary TRUSB with a median age of 64.2 years (range 34.9-89.2 years), PSA of 5.7 ng/ml (range 0.3-3,900 ng/ml), number of cores removed of 8.0 (range 1- 22) and TRUSPV of 36.4 cm(3) (range 9.6-212.0 cm(3)). CaP was diagnosed in 561 (36.4%) patients. A nomogram was constructed incorporating age at biopsy, race, PSA, body mass index, clinical stage, TRUSPV, number of cores removed, and family history of CaP. The concordance index when validated internally was 0.802. CONCLUSIONS: We have developed and internally validated a model predicting cancer detection in men undergoing TRUSB in a contemporary series. This model may assist clinicians in risk-stratifying potential candidates for TRUSB, potentially avoiding unnecessary or low-probability TRUSB.

Contemporary analysis of erectile, voiding, and oncologic outcomes following primary targeted cryoablation of the prostate for clinically localized prostate cancer.

PURPOSE: To evaluate erectile function (EF) and voiding function following primary targeted cryoablation of the prostate (TCAP) for clinically localized prostate cancer (CaP) in a contemporary cohort. MATERIALS AND METHODS: We retrospectively reviewed all patients treated between 2/2000-5/2006 with primary TCAP. Variables included age, Gleason sum, pre-TCAP prostate specific antigen (PSA), prostate volume, clinical stage, pre-TCAP hormonal ablation, pre-TCAP EF and American Urologic Association Symptom Score (AUASS). EF was recorded as follows: 1 = potent; 2 = sufficient for intercourse; 3 = partial/insufficient; 4 = minimal/insufficient; 5 = none. Voiding function was analyzed by comparing pre/post-TCAP AUASS. Statistical analysis utilized SAS software with p < 0.05 considered significant. RESULTS: After exclusions, 78 consecutive patients were analyzed with a mean age of 69.2 years and follow-up 39.8 months. Thirty-five (44.9%) men reported pre-TCAP EF level of 1-2. Post-TCAP, 9 of 35 (25.7%) regained EF of level 1-2 while 1 (2.9%) achieved level 3 EF. Median pre-TCAP AUASS was 8.75 versus 7.50 postoperatively (p = 0.39). Six patients (7.7%) experienced post-TCAP urinary incontinence. Lower pre-TCAP PSA (p = 0.008) and higher Gleason sum (p = 0.002) were associated with higher post-TCAP AUASS while prostate volume demonstrated a trend (p = 0.07). Post-TCAP EF and stable AUASS were not associated with increased disease-recurrence (p = 0.24 and p = 0.67, respectively). CONCLUSIONS: Stable voiding function was observed post-TCAP, with an overall incontinence rate of 7.7%. Further, though erectile dysfunction is common following TCAP, 25.7% of previously potent patients demonstrated erections suitable for intercourse. While long-term data is requisite, consideration should be made for prospective evaluation of penile rehabilitation following primary TCAP.

Contemporary analysis of erectile, voiding, and oncologic outcomes following primary targeted cryoablation of the prostate for clinically localized prostate cancer

PURPOSE: To evaluate erectile function (EF) and voiding function following primary targeted cryoablation of the prostate (TCAP) for clinically localized prostate cancer (CaP) in a contemporary cohort. MATERIALS AND METHODS: We retrospectively reviewed all patients treated between 2/2000-5/2006 with primary TCAP. Variables included age, Gleason sum, pre-TCAP prostate specific antigen (PSA), prostate volume, clinical stage, pre-TCAP hormonal ablation, pre-TCAP EF and American Urologic Association Symptom Score (AUASS). EF was recorded as follows: 1 = potent; 2 = sufficient for intercourse; 3 = partial/insufficient; 4 = minimal/insufficient; 5 = none. Voiding function was analyzed by comparing pre/post-TCAP AUASS. Statistical analysis utilized SAS software with p < 0.05 considered significant. RESULTS: After exclusions, 78 consecutive patients were analyzed with a mean age of 69.2 years and follow-up 39.8 months. Thirty-five (44.9 percent) men reported pre-TCAP EF level of 1-2. Post-TCAP, 9 of 35 (25.7 percent) regained EF of level 1-2 while 1 (2.9 percent) achieved level 3 EF. Median pre-TCAP AUASS was 8.75 versus 7.50 postoperatively (p = 0.39). Six patients (7.7 percent) experienced post-TCAP urinary incontinence. Lower pre-TCAP PSA (p = 0.008) and higher Gleason sum (p = 0.002) were associated with higher post-TCAP AUASS while prostate volume demonstrated a trend (p = 0.07). Post-TCAP EF and stable AUASS were not associated with increased disease-recurrence (p = 0.24 and p = 0.67, respectively). CONCLUSIONS: Stable voiding function was observed post-TCAP, with an overall incontinence rate of 7.7 percent. Further, though erectile dysfunction is common following TCAP, 25.7 percent of previously potent patients demonstrated erections suitable for intercourse. While long-term data is requisite, consideration should be made for prospective evaluation of penile rehabilitation following primary TCAP.