Michael M. Maddox

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

OBJECTIVEnTo 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.nnnMETHODSnSpecialized software was used to import patients 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.nnnRESULTSnWe 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 21xa0minutes, 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.nnnCONCLUSIONnPreoperative physical 3D models using available printing techniques can be constructed andxa0mayxa0potentially influence both patients and trainees understanding of renal malignancies.

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

OBJECTIVEnTo evaluate the effect of 3-dimensionally (3D) printed physical renal models with enhancing masses on medical trainee characterization, localization, and understanding of renal malignancy.nnnMETHODSnProprietary 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.nnnRESULTSnOverall 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.nnnCONCLUSIONnPhysical 3D models using readily available printing techniques improve trainees understanding and characterization of individual patients enhancing renal lesions.

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.

Crowdsourcing Assessment of Surgeon Dissection of Renal Artery and Vein During Robotic Partial Nephrectomy: A Novel Approach for Quantitative Assessment of Surgical Performance.

INTRODUCTIONnWe sought to describe a methodology of crowdsourcing for obtaining quantitative performance ratings of surgeons performing renal artery and vein dissection of robotic partial nephrectomy (RPN). We sought to compare assessment of technical performance obtained from the crowdsourcers with that of surgical content experts (CE). Our hypothesis is that the crowd can score performances of renal hilar dissection comparably to surgical CE using the Global Evaluative Assessment of Robotic Skills (GEARS).nnnMETHODSnA group of resident and attending robotic surgeons submitted a total of 14 video clips of RPN during hilar dissection. These videos were rated by both crowd and CE for technical skills performance using GEARS. A minimum of 3 CE and 30 Amazon Mechanical Turk crowdworkers evaluated each video with the GEARS scale.nnnRESULTSnWithin 13 days, we received ratings of all videos from all CE, and within 11.5 hours, we received 548 GEARS ratings from crowdworkers. Even though CE were exposed to a training module, internal consistency across videos of CE GEARS ratings remained low (ICCu2009=u20090.38). Despite this, we found that crowdworker GEARS ratings of videos were highly correlated with CE ratings at both the video level (Ru2009=u20090.82, pu2009<u20090.001) and surgeon level (Ru2009=u20090.84, pu2009<u20090.001). Similarly, crowdworker ratings of the renal artery dissection were highly correlated with expert assessments (Ru2009=u20090.83, pu2009<u20090.001) for the unique surgery-specific assessment question.nnnCONCLUSIONSnWe conclude that crowdsourced assessment of qualitative performance ratings may be an alternative and/or adjunct to surgical experts ratings and would provide a rapid scalable solution to triage technical skills.

Robotic Partial Nephrectomy for Clinical Stage T1b Tumors: Intermediate Oncologic and Functional Outcomes

OBJECTIVEnThe objective of this study was to examine our intermediate oncologic and functional outcomes of robotic partial nephrectomy for clinical T1b tumors. Partial nephrectomy has become the gold standard of treatment for small renal masses. Recently, indications for minimally invasive partial nephrectomy have extended to larger and more complicated renal masses in some centers.nnnMATERIALS AND METHODSnBetween July 2008 and September 2013, 241 robotic partial nephrectomies were performed at our institution, including 46 for clinical ≥ T1b tumors. We reviewed the intermediate-term functional and oncologic outcomes of this cohort of patients.nnnRESULTSnOf the 46 patients, the median age was 55.5 years (interquartile range [IQR], 51-68 years) with a median body mass index of 31.6 (IQR, 27.4-38.9), tumor diameter of 5.0 cm (IQR, 4.1-5.2 cm), and RENAL nephrometry score of 7.1 (range, 5-11). Renal cell carcinoma was confirmed in 35 patients, and 11 patients had benign pathology. There was 1 patient with an established positive margin and 2 patients had a focal positive margin. At a median follow-up of 24.3 months (range, 2.3-61.1 months), the overall, recurrence-free and cancer-specific survival was 97.1%, 97.1%, and 100%, respectively. No patient progressed to dialysis postoperatively and there was no significant difference between preoperative and postoperative serum creatinine or estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation.nnnCONCLUSIONnBecause of the many adverse medical effects of chronic renal insufficiency, the indications for partial nephrectomy are expanding at many institutions. We demonstrated that robotic partial nephrectomy is a safe and efficacious procedure for the treatment of T1b renal tumors with excellent intermediate oncologic and functional outcomes.

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.

The emergence of extracellular vesicles in urology: fertility, cancer, biomarkers and targeted pharmacotherapy

Extracellular vesicles (EV) are small membrane-bound vesicles enriched in a selective repertoire of mRNA, miRNA, proteins and cell surface receptors from parental cells and are actively involved in the transmission of inter and intracellular signals. Cancer cells produce EV that contain cargo including DNA, mRNA, miRNA and proteins that allow EV to create epigenetic changes in target cells both locally and systemically. Cancer-derived EV play critical roles in tumorigenesis, cancer cell migration, metastasis, evasion of host immune defense, chemoresistance, and they promote a premetastatic niche favourable to micrometastatic seeding. Their unique molecular profiles acquired from originator cells and their presence in numerous body fluids, including blood and urine, make them promising candidates as biomarkers for prostate, renal and bladder cancers. EV may ultimately serve as targets for therapy and as platforms for personalized medicine in urology. As urologic malignancy comprises 28% of new solid tumour diagnoses and 15% of cancer-related deaths, EV-related research is rapidly emerging and providing unique insights into disease progression. In this report, we review the current literature on EV in the setting of genitourinary fertility and malignancy.

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.

Histopathologic changes after bipolar resection of the prostate: depth of penetration of bipolar thermal injury.

BACKGROUND AND PURPOSEnWhile the power needed to initiate bipolar vaporization is higher than conventional monopolar resection, the energy needed to maintain bipolar vaporization is significantly lower and may result in less thermal tissue injury. This may have implications for hemostasis, scarring, and perioperative morbidity. The objective of this study is to assess histopathologic changes in prostatic tissue after bipolar transurethral vaporization of the prostate.nnnPATIENTS AND METHODSnMale patients older than 40 years with a diagnosis of benign prostatic hyperplasia (BPH) who elected to undergo bipolar transurethral vaporization of the prostate were included in this study. Patients were excluded if they had a previous transurethral resection of the prostate (TURP) or prostate radiation therapy. An Olympus button vaporization electrode was used to vaporize prostate tissue. A loop electrode was then used to obtain a deep resection specimen. The vaporized and loop resection surfaces were inked and sent for pathologic analysis to determine the presence of gross histologic changes and the depth of penetration of the bipolar vaporization current.nnnRESULTSnA total of 12 men underwent bipolar TURP at standard settings of 290u2009W cutting and 145u2009W coagulation current. Mean patient age was 70±10.2 years (range 56-88 years). Mean surgical time was 48.7±20.2 minutes (range 30-89u2009min). Mean depth of thermal injury was 2.4±0.84u2009mm (range 0.3-3.5u2009mm). Histopathologic evaluation demonstrated thermal injury in all specimens, but no gross char was encountered.nnnCONCLUSIONSnIn bipolar systems, resection takes place at much lower peak voltages and temperatures compared with monopolar systems. Theoretically, this leads to less collateral thermal damage and tissue char. Our tissue study illustrates that the button vaporization electrode achieves a much larger depth of penetration than previous studies of bipolar TURP. This may be because thermal injury represents a gradual continuum of histologic changes.

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 4.4xa0cm, warm ischemia time was 25xa0min, 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 (186xa0cc vs 236; pxa0=xa00.01). 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.