Single-stage Xi® robotic radical nephroureterectomy for upper tract urothelial carcinoma: surgical technique and outcomes.

BACKGROUND: Radical nephroureterectomy (RNU) represents the standard of care for high grade upper tract urothelial carcinoma (UTUC). Open and laparoscopic approaches are well-established treatments, but evidence regarding robotic RNU is growing. The introduction of the Xi® system facilitates the implementation of this multi-quadrant procedure. The aim of this video-article is to describe the surgical steps and the outcomes of Xi® robotic RNU. METHODS: Single stage Xi® robotic RNU without patients repositioning and robot re-docking were done between 2015 and 2019 and collected in a large worldwide multi-institutional study, the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST). Institutional review board approval and data share agreement were obtained at each center. Surgical technique is described in detail in the accompanying video. Descriptive statistics of baseline characteristics and surgical, pathological, and oncological outcomes were analyzed. RESULTS: Overall, 148 patients were included in the analysis; 14% had an ECOG >1 and 68.2% ASA ≥3. Median tumor dimension was 3.0 (IQR:2.0-4.2) cm and 34.5% showed hydronephrosis at diagnosis. Forty-eight% were cT1 tumors. Bladder cuff excision and lymph node dissection were performed in 96% and 38.1% of the procedures, respectively. Median operative time and estimated blood loss were 215.5 (IQR:160.5-290.0) minutes and 100.0 (IQR: 50.0-150.0) mL, respectively. Approximately 56% of patients took opioids during hospital stay for a total morphine equivalent dose of 22.9 (IQR:16.0-60.0) milligrams equivalent. Post-operative complications were 26 (17.7%), with 4 major (2.7%). Seven patients underwent adjuvant chemotherapy, with median number of cycles of 4.0 (IQR:3.0-6.0). CONCLUSIONS: Single stage Xi® RNU is a reproducible and safe minimally invasive procedure for treatment of UTUC. Additional potential advantages of the robot might be a wider implementation of LND with a minimally invasive approach.

A Preoperative Nomogram to Predict Renal Function Insufficiency for Cisplatin-based Adjuvant Chemotherapy Following Minimally Invasive Radical Nephroureterectomy (ROBUUST Collaborative Group).

BACKGROUND: Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU). OBJECTIVE: To create a model predicting renal function decline after minimally invasive RNU. DESIGN, SETTING, AND PARTICIPANTS: A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m2 at 3 mo after RNU. Patients with baseline eGFR >50 ml/min/1.73 m2 (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR <50 ml/min/1.73 m2 was built based on the coefficients of the least absolute shrinkage and selection operation (LASSO) logistic regression. The discrimination, calibration, and clinical use of the nomogram were investigated. RESULTS AND LIMITATIONS: The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p < 0.001) and cancer-specific death risk (HR: 5.19, p < 0.001) was statistically significant. The limitation mainly lies in its retrospective design. CONCLUSIONS: A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection. PATIENT SUMMARY: We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.

Folate-targeted intraoperative fluorescence, OTL38, in robotic-assisted laparoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and efficacy of OTL38, a folate-targeted, intraoperative fluorescence agent, in patients undergoing robotic-assisted laparoscopic partial nephrectomy. METHODS: Patients with proven or suspected localized renal cell carcinoma at a single academic institution were selected from 2016 to 2018. Patients received one dose of OTL38 at 0.025 mg/kg prior to robotic-assisted laparoscopic partial nephrectomy. The da Vinci Fluorescence Imaging Vision System was used to identify the tumor and inspect for residual disease after resection. Immunohistochemistry was performed to quantify folate receptor alpha in both the tumor and surrounding normal parenchyma. Patient follow-up was 1 month. Outcome data included descriptive statistics of the patient cohort and surgeon and pathologist surveys. RESULTS: Ten cases were performed. Mean patient age was 62.9 years (range = 50-70). Mean tumor size was 2.45 cm. Pathologic tumor stages ranged from T1a-T3a. Histologic tumor types included clear cell, chromophobe, type 1 papillary renal cell carcinoma and oncocytoma. The tumors did not fluoresce, while the surrounding normal parenchyma did show fluorescence. No adverse reactions were seen. Staining for folate receptor alpha was localized to the proximal renal tubules. Average staining in normal surrounding renal parenchyma was significantly greater than staining observed in tumor tissue (0.2086 vs 0.0467; p = 0.002). The mean difference in staining between tumor tissue and surrounding normal renal parenchyma was 0.1619 (95% CI = 0.0796-0.2442). CONCLUSIONS: Based on our initial experience, OTL38 shows potential as a safe, effective and easy to use tool to improve visualization and resection of renal tumors.

Clear cell papillary renal cell carcinoma: Characteristics and survival outcomes from a large single institutional series.

OBJECTIVES: To investigate the clinical characteristics and survival outcomes of a large clear cell papillary renal cell carcinoma cohort. METHODS AND MATERIALS: A retrospective review of patients with clear cell papillary renal cell carcinoma at a single academic center was performed after Institutional Review Board approval. Patients underwent either partial or radical nephrectomy from September 2009 to July 2019. Demographic and clinical characteristics, recurrence, and cancer specific and overall survival were reported. RESULTS: A total of 90 patients were included in the study. Median follow up was 26.5 months. Median age was 61 (range 27 to 87). 47.8% of patients were African American. 26.7% of patients had end stage renal disease. 37.8% had multifocal renal tumors. 48.9% underwent partial nephrectomy, while the remainder underwent radical nephrectomy. 43.3% underwent an open surgical approach, 40.0% a robotic approach, and 16.7% a laparoscopic approach. Pathologic stage included T1a (90.0%), T1b (1.1%), and T2b (8.9%). Fuhrman grades 1-3 were present in 18.9%, 77.8%, and 3.3% of patients, respectively. There were no cancer specific deaths. There was one local recurrence and no metastases. The overall survival at a median follow up of 26.5 months was 92.1% (95% confidence interval 83.1%-96.4%). CONCLUSIONS: Clear cell papillary renal cell carcinoma typically presents at a low stage and grade and has favorable survival outcomes. A nephron-sparing approach to treatment should be considered when feasible due to the tumor's indolent nature and propensity towards multifocality.

Machine Learning and Artificial Intelligence in Surgical Fields.

Artificial intelligence (AI) and machine learning (ML) have the potential to improve multiple facets of medical practice, including diagnosis of disease, surgical training, clinical outcomes, and access to healthcare. There have been various applications of this technology to surgical fields. AI and ML have been used to evaluate a surgeon's technical skill. These technologies can detect instrument motion, recognize patterns in video recordings, and track the physical motion, eye movements, and cognitive function of the surgeon. These modalities also aid in the advancement of robotic surgical training. The da Vinci Standard Surgical System developed a recording and playback system to help trainees receive tactical feedback to acquire more precision when operating. ML has shown promise in recognizing and classifying complex patterns on diagnostic images and within pathologic tissue analysis. This allows for more accurate and efficient diagnosis and treatment. Artificial neural networks are able to analyze sets of symptoms in conjunction with labs, imaging, and exam findings to determine the likelihood of a diagnosis or outcome. Telemedicine is another use of ML and AI that uses technology such as voice recognition to deliver health care remotely. Limitations include the need for large data sets to program computers to create the algorithms. There is also the potential for misclassification of data points that do not follow the typical patterns learned by the machine. As more applications of AI and ML are developed for the surgical field, further studies are needed to determine feasibility, efficacy, and cost.

Indwelling ureteric stents: Patterns of use and nomenclature.

Objectives: To evaluate ureteric stenting practice patterns amongst a range of academic and community urologists, and to examine the nomenclature used to identify an indwelling ureteric stent from both our questionnaire and from a review of the literature. Subjects and methods: A 16-question, peer-reviewed online survey was distributed to members of the Mid-Atlantic American Urological Association. Responses were collected over a 1-month period. Questions included demographics, ureteric stenting practice patterns, and utilization of stenting nomenclature. Inappropriate use of nomenclature was defined as a mismatch between the visually depicted stents and the written description amongst urologists. Trends in ureteric stenting and nomenclature usage were tabulated and analyzed. Results: Of 863 members, 105 (12.2%) responded to the survey. There was a wide variety of practice settings, with the single-specialty group (44.2%) and academic/university (27.9%) being the two most common. Most providers used both cystoscopy and fluoroscopy to place stents (87.5%) as compared to fluoroscopy alone (12.5%). Most urologists (63.5%) removed stents with cystoscopy as compared to using a stent string (36.5%). While about half (51.0%) of the respondents left stents in situ for ≤3 months, many respondents (43.3%) felt comfortable with maximum dwell times of up to 6 months. The most commonly placed stent was the double pigtail stent (80.8%). However, most respondents inappropriately described this stent design as a Double J stent (72.1%). In the recent literature, 80% of articles clearly defined as using double pigtail stents, incorrectly identified their stent as a 'Double J'. Conclusions: Variations in ureteric stenting practice patterns exist amongst community and academic urologists. Although most urologists utilize double pigtail ureteric stents, the majority inaccurately identified this stent design as a Double J. We propose use of the term 'indwelling ureteric stent' (IUS) unless describing any specific stent design.

Urologic Surgery and COVID-19: How the Pandemic Is Changing the Way We Operate.

The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on all aspects of health care, including surgical procedures. For urologists, it has affected and will continue to influence how we approach the care of patients preoperatively, intraoperatively, and postoperatively. A risk-benefit assessment of each patient undergoing surgery should be performed during the COVID-19 pandemic based on the urgency of the surgery and the risk of viral illness and transmission. Patients with advanced age and comorbidities have a higher incidence of mortality. Routine preoperative testing and symptom screening is recommended to identify those with COVID-19. Adequate personal protective equipment (PPE) for the surgical team is essential to protect health care workers and ensure an adequate workforce. For COVID-19 positive or suspected patients, the use of N95 respirators is recommended if available. The anesthesia method chosen should attempt to minimize aerosolization of the virus. Negative pressure rooms are strongly preferred for intubation/extubation and other aerosolizing procedures for COVID-19 positive patients or when COVID status is unknown. Although transmission has not yet been shown during laparoscopic and robotic procedures, efforts should be made to minimize the risk of aerosolization. Ultra-low particulate air filters are recommended for use during minimally invasive procedures to decrease the risk of viral transmission. Thorough cleaning and sterilization should be performed postoperatively with adequate time allowed for the operating room air to be cycled after procedures. COVID-19 patients should be separated from noninfected patients at all levels of care, including recovery, to decrease the risk of infection. Future directions will be guided by outcomes and infection rates as social distancing guidelines are relaxed and more surgical procedures are reintroduced. Recommendations should be adapted to the local environment and will continue to evolve as more data become available, the shortage of testing and PPE is resolved, and a vaccine and therapeutics for COVID-19 are developed.

Prostatic Stromal Tumors of Uncertain Malignant Potential.

We present a 53-year-old man with a multilocular solid and cystic mass measuring 19 cm on cross-sectional imaging. After undergoing pelvic mass excision, final histopathology confirmed the diagnosis of primary prostatic stromal tumor of uncertain malignant potential (STUMP). Prostatic STUMPs are rare mesenchymal tumors with diverse histologic patterns. They are distinct from prostatic stromal sarcomas as they do not behave aggressively, although some may occasionally demonstrate local recurrence after resection. Due to their unpredictable malignant potential, lack of correlation between histologic patterns, and sarcomatous differentiation, these patients warrant surgical excision and close follow-up.

Neurotrophin therapy improves recovery of the neuromuscular continence mechanism following simulated birth injury in rats.

AIMS: Stress urinary incontinence (SUI) affects women both acutely and chronically after vaginal delivery. Current SUI treatments assume the neuromuscular continence mechanism, comprised of the pudendal nerve (PN) and external urethral sphincter (EUS), is either intact or irreparable. This study investigated the ability of neurotrophin therapy to facilitate recovery of the neuromuscular continence mechanism. METHODS: Virgin, Sprague Dawley rats received simulated childbirth injury or sham injury and treatment with continuous infusion of brain-derived neurotrophic factor (BDNF) or saline placebo to the site of PN injury. Continence was assessed by leak point pressure (LPP) and EUS electromyography (EMG) 14 and 21 days after injury. Structural recovery was assessed histologically. Molecular assessment of the muscular and neuroregenerative response was determined via measurement of EUS BDNF and PN ß(II) -tubulin expression respectively, 4, 8, and 12 days after injury. RESULTS: Following injury, LPP was significantly reduced with saline compared to either BDNF treatment or sham injury. Similarly, compared to sham injury, resting EUS EMG amplitude and firing rate, as well as amplitude during LPP were significantly reduced with saline but not BDNF treatment. Histology confirmed improved EUS recovery with BDNF treatment. EUS BDNF and PN ß(II)-tubulin expression demonstrated that BDNF treatment improved the neurogenerative response and may facilitate sphincteric recovery. CONCLUSIONS: Continuous targeted neurotrophin therapy accelerates continence recovery after simulated childbirth injury likely through stimulating neuroregeneration and facilitating EUS recovery and re-innervation. Neurotrophins or other therapies targeting neuromuscular regeneration may be useful for treating SUI related to failure of the neuromuscular continence mechanism.

Pudendal nerve stretch reduces external urethral sphincter activity in rats.

PURPOSE: Most animal models of stress urinary incontinence simulate maternal injuries of childbirth since delivery is a major risk factor but they do not reproduce the nerve stretch known to occur during human childbirth. We hypothesized that pudendal nerve stretch produces reversible dysfunction of the external urethral sphincter. MATERIALS AND METHODS: Female virgin Sprague-Dawley® rats were anesthetized with urethane. Bilateral pudendal nerve stretch or sham injury was performed for 5 minutes. External urethral sphincter electromyography and leak point pressure were recorded immediately before and after, and 10, 30, 60 and 120 minutes after pudendal nerve stretch. Post-pudendal nerve stretch results were compared to prestretch values and to values in sham injured animals. The pudendal nerves underwent qualitative histological assessment. The nucleus of Onuf was evaluated by immunohistochemistry and polymerase chain reaction for ß-APP and c-Fos expression as markers of neuronal activity and injury. RESULTS: A total of 14 rats underwent bilateral pudendal nerve stretch (9) or sham injury (5). Each nerve was stretched a mean ± SEM of 74% ± 18% on the left side and 63% ± 13% on the right side. Electromyography amplitude decreased significantly immediately after stretch compared to before stretch and after sham injury (p = 0.003) but it recovered by 30 minutes after stretch. There was no significant change in leak point pressure at any time. Two hours after injury histology showed occasional neuronal degeneration. ß-APP and c-Fos expression was similar in the 2 groups. CONCLUSIONS: Acute pudendal nerve stretch produces reversible electrophysiological dysfunction but without leak point pressure impairment. Pudendal nerve stretch shows promise in modeling injury. It should be tested as part of a multi-injury, chronic, physiological model of human childbirth injury.

Quantitative evaluation of electrodes for external urethral sphincter electromyography during bladder-to-urethral guarding reflex.

PURPOSE: Accuracy in the recording of external urethral sphincter (EUS) electromyography (EMG) is an important goal in the quantitative evaluation of urethral function. The aim of this study was to quantitatively compare electrode recordings taken during tonic activity and leak point pressure (LPP) testing. METHODS: Several electrodes, including the surface electrode (SE), concentric electrode (CE), and wire electrode (WE), were placed on the EUS singly and simultaneously in six female Sprague-Dawley rats under urethane anesthesia. The bladder was filled via a retropubic catheter while LPP testing and EUS EMG recording were done. Quantitative baseline correction of the EUS EMG signal was performed to reduce baseline variation. Amplitude and frequency of 1-s samples of the EUS EMG signal were measured before LPP (tonic activity) and during peak LPP activity. RESULTS: The SE, CE, and WE signals demonstrated tonic activity before LPP and an increase in activity during LPP, suggesting that the electrodes accurately recorded EUS activity during tonic activity and during the bladder-to-EUS guarding reflex, regardless of the size or location of detection areas. SE recordings required significantly less baseline correction than both CE and WE recordings. The activity in CE-recorded EMG was significantly higher than that of the SE and WE both in single and simultaneous recordings. CONCLUSIONS: These electrodes may be suitable for testing EUS EMG activity. The SE signal had significantly less baseline variation and the CE detected local activity more sensitively than the other electrodes, which may provide insight into choosing an appropriate electrode for EUS EMG recording.

Dual simulated childbirth injury delays anatomic recovery.

A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.