Molecular determinants and signaling effects of PKA RIα phase separation.

Spatiotemporal regulation of intracellular signaling molecules, such as the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures proper cellular function. Liquid-liquid phase separation (LLPS) of the ubiquitous PKA regulatory subunit RIα promotes cAMP compartmentation and signaling specificity. However, the molecular determinants of RIα LLPS remain unclear. Here, we reveal that two separate dimerization interfaces, combined with the cAMP-induced unleashing of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence, drive RIα condensate formation in the cytosol of mammalian cells, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RIα pseudosubstrate region is critically involved in forming a non-canonical R:C complex, which recruits active PKA-C to RIα condensates to maintain low basal PKA activity in the cytosol. Our results suggest that RIα LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity.

Molecular Determinants and Signaling Effects of PKA RIα Phase Separation.

Spatiotemporal regulation of intracellular signaling molecules, such as the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures the specific execution of various cellular functions. Liquid-liquid phase separation (LLPS) of the ubiquitously expressed PKA regulatory subunit RIα was recently identified as a major driver of cAMP compartmentation and signaling specificity. However, the molecular determinants of RIα LLPS remain unclear. Here, we reveal that two separate dimerization interfaces combined with the cAMP-induced release of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence are required to drive RIα condensate formation in cytosol, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RIα pseudosubstrate region is critically involved in the formation of a non-canonical R:C complex, which serves to maintain low basal PKA activity in the cytosol by enabling the recruitment of active PKA-C to RIα condensates. Our results suggest that RIα LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity.

A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-ß1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial.

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

Multi-material three dimensional printed models for simulation of bronchoscopy.

BACKGROUND: Bronchoscopy involves exploration of a three-dimensional (3D) bronchial tree environment using just two-dimensional (2D) images, visual cues and haptic feedback. Sound knowledge and understanding of tracheobronchial anatomy as well as ample training experience is mandatory for technical mastery. Although simulated modalities facilitate safe training for inexperienced operators, current commercial training models are expensive or deficient in anatomical accuracy, clinical fidelity and patient representation. The advent of Three-dimensional (3D) printing technology may resolve the current limitations with commercial simulators. The purpose of this report is to develop and test the novel multi-material three-dimensional (3D) printed airway models for bronchoscopy simulation. METHODS: Using material jetting 3D printing and polymer amalgamation, human airway models were created from anonymized human thoracic computed tomography images from three patients: one normal, a second with a tumour obstructing the right main bronchus and third with a goitre causing external tracheal compression. We validated their efficacy as airway trainers by expert bronchoscopists. Recruited study participants performed bronchoscopy on the 3D printed airway models and then completed a standardized evaluation questionnaire. RESULTS: The models are flexible, life size, anatomically accurate and patient specific. Five expert respiratory physicians participated in validation of the airway models. All the participants agreed that the models were suitable for training bronchoscopic anatomy and access. Participants suggested further refinement of colour and texture of the internal surface of the airways. Most respondents felt that the models are suitable simulators for tracheal pathology, have a learning value and recommend it to others for use in training. CONCLUSION: Using material jetting 3D printing to create patient-specific anatomical models is a promising modality of simulation training. Our results support further evaluation of the printed airway model as a bronchoscopic trainer, and suggest that pathological airways may be simulated using this technique.

Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial.

Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.

Blood-borne biomarkers of osteosarcoma: A systematic review.

Osteosarcoma is the most common type of primary malignant bone tumor in children and young adults. Development of clinically useful biomarkers has the potential to improve treatments. The aim of this review was to investigate the recent literature assessing the utility of biomarkers for osteosarcoma. A detailed literature search was performed, with hand searches for related research publications. The search was limited to publications in English between January 2007 and February 2017. Of 286 studies identified, 24 met the inclusion criteria. There is a wide range of osteosarcoma biomarkers identified which act as clinical prognostic factors in patient outcome.

Robotic left lower sleeve lobectomy with bronchoplasty for the removal of a carcinoid tumour.

Lung carcinoid tumours constitute approximately 1-2% of all pulmonary tumours. They are derived from enterochromaffin cells, which are also known as 'Kulchitsky cells' and generally have indolent growth and development patterns. Carcinoid tumours are categorized as typical or atypical, depending on the number of mitoses per high power field and the presence of necrosis. In terms of management, surgical resection has been recognized to be the standard treatment for pulmonary carcinoid tumours. To our knowledge, the da Vinci system and robotic surgery have not been applied in sleeve lobectomies and bronchoplasty for the removal of carcinoid tumours in the United Kingdom. Therefore, we present a case of a sleeve lobectomy with bronchoplasty procedure for the removal of a carcinoid tumour located in the left lower lobe of the patient. The bronchus was repaired using a V-lock suture & Prolene sutures with the surgery performed using the da Vinci robotic surgical system.

Robotic pericardial patch repair of the bronchus intermedius after bronchogenic cyst removal.

Bronchogenic cysts are often asymptomatic mediastinal masses that are usually diagnosed as incidental findings. Surgical resection can be performed with robotic surgery, and if repair of the airway is needed, this can be achieved by direct closure or by applying a pericardial patch. We present a case of a 45-year-old woman diagnosed with a mass in the visceral mediastinum. She had undergone resection adopting a 4-armed, completely portal robotic technique. However, the removal of the cyst had led to a large tear in the bronchus intermedius. The bronchus was then repaired with a 2.4-cm-long pericardial patch sutured with the V-lock sutures. The entire procedure was performed in a total span of 189 min, and the patient was discharged on postoperative Day 2. The robotic platform, with articulated instruments, allowed complex suturing while conversion was not required. To our knowledge, the robotic surgery has not been applied in bronchial repairs by pericardial patches, and this case is the first of its kind.

FDG PET/CT in the liver: lesions mimicking malignancies.

PURPOSE: 18F-fluorodeoxyglucose (FDG) PET/CT is invaluable in managing liver lesions, in particular in the evaluation of suspected liver metastases. It is both sensitive and specific in detecting liver metastases from a wide range of primary cancers, and may change clinical management, most commonly by detecting additional lesions and decreasing the number of futile surgeries. However, some benign lesions may also show increased metabolic activity which can lead to false positive PET findings. We describe some of these lesions and their imaging characteristics that may help in differentiating them from malignant metastases. METHODS: e reviewed all whole body FDG PET/CT studies performed over a 5-year period in our institution, and identified those with focal liver lesions showing increased FDG uptake for which histological results were available. RESULTS: majority of lesions showing increased metabolic activity were due to malignant disease, such as metastases or primary liver tumours. However, we also found increased FDG uptake in non-neoplastic lesions such as Cryptococcosis, abscesses, and secondary inflammation from cholecystitis. Increased metabolic activity was also seen in some benign neoplasms such as hepatic adenomas and hemangioendotheliomas. CONCLUSION: DG PET/CT is currently the most sensitive non-invasive imaging modality for the detection of hepatic metastases, particularly from the gastrointestinal tract. False positive results are rare, and have been described mainly in abscesses. However, other lesions can also show increased metabolic activity, and failure to differentiate these from metastases may result in inappropriate treatment.

Developing technical expertise in robot-assisted laparoscopic prostatectomy in a moderate-volume center through a proctor-based team approach.

Our aim is to report our preliminary experience of a proctor-based team approach in robot-assisted laparoscopic prostatectomy (RALP) for the treatment of localized prostate cancer. Data was collected between December 2008 and February 2012. RALP was performed on 100 consecutive patients with prostate cancer by a team of five urologists proctored by two fellowship-trained surgeons from a single hospital. Clinical and pathological data of these patients were reviewed. The mean age of the patients was 66 years (range 48-76). Clinical stages were 82 % cT1c, 3 % cT1b, 13 % cT2a and 2 % cT3a disease. Preoperative mean prostate-specific antigen level was 11.33 ng/ml (SD 10.47). Mean operative time was 342 min and mean blood loss was 717 ml (SD 988). Mean hospital stay and duration of the indwelling catheter were 3.2 days (SD 1.8) and 12.6 days (SD 8.5), respectively. Pathological staging showed 65 patients with pT2a (65 %) disease and 33 patients with pT3a (33 %) disease. Thirty-five patients (35 %) had positive surgical margins. Eighteen patients underwent adjuvant radiotherapy. Overall postoperative complication rate was 14 %. There were six Clavien grade 1 complications, seven Clavien grade 2 complications and one Clavien grade 3 complication. At mean follow-up of 36 months, 100 % of patients remained free of biochemical recurrence with continence at 70 %. Our proctor-based team approach will continue to improve each surgeon's technical competency. He or she will continue to improve and gradually move on to achieving his or her outcomes learning curve.

A guide to requesting outpatient and emergency radiographs.

Radiology is an important adjunct to clinical practice, but for many clinicians, requesting X-rays was something that was learnt on the job. This article provides guidelines on when and how to request X-rays for acute conditions such as head and cervical spine trauma, suspected rib and extremity fractures, low back pain and acute abdominal pain. We also highlight what to write in the request form, in order to obtain maximum value from the examination and allow the radiologist to generate a useful, accurate report.

PILL series. The solitary pulmonary nodule.

The solitary pulmonary nodule on chest X-ray (CXR) is a common problem in pulmonary medicine. Its presence raises the question of lung cancer. As five-year survival after resection of a solitary bronchogenic carcinoma can be as high as 80%, prompt evaluation is crucial. This should begin with a cancer risk assessment based on clinical and radiographic factors. The risk and benefits of surgery should next be assessed, and together with the patient's preferences, a management plan can be decided upon. Surgery is recommended for patients at high risk of malignancy with a low surgical risk, while careful observation is adopted for patients at low risk of malignancy coupled with a high surgical risk. Further diagnostic tests may be warranted to aid in this decision process. Although CXR is not useful for lung cancer screening, low-dose computed tomography imaging is increasingly recommended for individuals at high risk for lung cancer.

Cystolithotomy during robotic radical prostatectomy: Single-stage procedure for concomitant bladder stones.

Asymptomatic concomitant vesical calculi are an occasional finding on routine radiologic staging and evaluation of patients with early prostate cancer. We report the first case of single-stage robotic cystolithotomy for multiple bladder stones in a 64-year-old man undergoing robotic-assisted radical prostatectomy, and discuss the approaches available for ensuring complete stone clearance in this unique setting. We show that concomitant bladder stone extraction during robotic-assisted radical prostatectomy is feasible and does not add significantly to operative time. This technique avoids the need to undergo additional general anesthetic procedures with potential complications such as bleeding, urethral stricture formation, and bladder perforation, prior to the prostatectomy.

Clinical and pathologic predictors of Gleason sum upgrading in patients after radical prostatectomy: results from a single institution series.

OBJECTIVES: Preoperative Gleason scores (GSs) are often upgraded after pathologic examination of the prostate following radical prostatectomy (RP). There have been disparate reports of the impact of different factors as predictors of GS upgrading after RP. We sought to study the robustness of frequently reported predictors in an unselected single institution cohort. PATIENTS AND METHODS: A total of 684 patients with biopsy-proven prostate cancer treated with RP between 2004 and 2007 were included in the study. The association between clinical and pathologic parameters and GS upgrading was retrospectively evaluated. Logistic regression analysis was used to identify predictors of pathologic grading changes. Likelihood of upgrading was compared between tertile groups for prostate volume and prostate-specific antigen (PSA) density using χ(2) analysis and multivariate logistic regression. Pathologic outcomes were compared between cases with and without GS upgrading. RESULTS: The overall mean age was 64.3 years, with median PSA level of 7.04 ng/ml. Overall, 203 cases (29.7%) were upgraded, whereas 481 patients (70.3%) were downgraded or had identical biopsy and pathologic GS after RP. Patients with prostate volume of <31 g were upgraded in 32.6% of the cases compared with 21.9% in patients with prostate volume of >45 g (P = 0.020). On multivariate analysis preoperative PSA (P < 0.0001), prostate volume (P < 0.0001), and PSA density (P < 0.0001) were predictive of Gleason sum upgrading. Upgraded patients were more likely to have extracapsular extension, seminal vesicle invasion, positive surgical margins, and lymphonodular invasion at RP (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: Smaller prostate volume and higher PSA level are associated with clinically significant upgrading of GS. PSA density as a function of both is a significant predictor of GS upgrading in low- and high-risk patients. This may be of relevance in the pretreatment risk assessment of prostate cancer patients.

Neuroanatomic basis for traction-free preservation of the neural hammock during athermal robotic radical prostatectomy.

PURPOSE OF REVIEW: Much of the progress achieved in the past two decades in improving potency outcomes after radical prostatectomy has resulted from an improved appreciation of the anatomic basis of the nerves responsible for erection. We review the current literature evaluating the neuroanatomy of prostate and operative strategies for better preservation of sexual function. RECENT FINDINGS: Recent studies suggest an alternative and more complex course of nerves than previously described. Periprostatic nerves can be divided into three broad surgically identifiable zones: the proximal neurovascular plate, the predominant neurovascular bundle, and the accessory neural pathways. Better appreciation of the variable and often invisible anatomical course of the cavernosal nerves continues to engender innovations in surgical technique to optimize their preservation. SUMMARY: Improved anatomic understanding has optimized surgical technique in order to improve potency outcomes following radical prostatectomy.

Optimizing vesicourethral anastomosis healing after robot-assisted laparoscopic radical prostatectomy: lessons learned from three techniques in 1900 patients.

BACKGROUND AND PURPOSE: Creation of an optimally apposed, tension-free, well-supported vesicourethral anastomosis remains the cornerstone for anastomotic healing after radical prostatectomy. We report the effect of three techniques of bladder neck reconstruction during robot-assisted radical prostatectomy on anastomotic leak, stricture formation, and continence recovery. PATIENTS AND METHODS: Between January 2005 to September 2009, 1900 consecutive patients underwent robotic-assisted laparoscopic prostatectomy (RALP) by a single surgeon. Of these, the first 214 underwent vesicourethral conventional anastomosis (CA); the next 303 men underwent anterior reconstruction (AR) only; and last 1383 men underwent total anatomic restoration (TR). Data elements included patient age, body mass index, preoperative biopsy Gleason score and prostate-specific antigen level, prostate volume, total operative time, console time, time for performing vesicourethral anastomosis, estimated blood loss, tumor stage, and margin status on final pathologic findings. Primary end points were rates of clinically significant anastomotic leaks, bladder neck contractures, and time to return of continence. Chi-square and Fisher exact tests were used for analysis of categoric variables. The Cox proportional hazard model was used for both univariate and multivariate analysis. RESULTS: Clinically significant anastomotic leakage and bladder neck strictures were significantly fewer in the reconstructed groups (2.3% vs 1.0% vs 0.3% and 3.7% vs 1.3% vs 0.5% in the CA, AR, and TR groups, P < 0.01). Continence rates at 1, 6, 12, 26, and 52 weeks after RALP were also significantly better at all time points with AR and TR compared with CA alone (P < 0.001). CONCLUSIONS: TR of the continence mechanism optimizes vesicourethral anastomosis healing and hastens early continence return after RALP.

Clinicopathological strategies to identify contralateral prostate cancer involvement in potential candidates for focal therapy.

OBJECTIVE: To identify the magnitude and possible predictors of contralateral lobe involvement and contralateral extraprostatic extension (EPE) in prostatic biopsy-defined localized unilateral cancers. PATIENTS AND METHODS: Between January 2005 and August 2009, 1861 patients underwent robotic-assisted radical prostatectomy at the authors' institution. A total of 1114 had unilateral disease on preoperative biopsy. Final histopathology reports of these patients were reviewed. RESULTS: Of the 1114 patients with unilateral disease on biopsy, 867 (77.9%) had contralateral or bilateral disease on final histopathology. EPE was found in 132 patients (11.9%). Twenty patients (1.8%) had contralateral EPE involvement. High-grade prostatic intraepithelial neoplasm (HGPIN) on biopsy was the significant predictor of contralateral lobe involvement on both univariate (P = .02; odds ratio [OR] = 1.791) and multivariate analysis (P = .004; OR = 2.677). Clinical stage T2 was the significant predictor of contralateral EPE on both univariate (P = .012; OR = 5.250) and multivariate analysis (P = .007; OR = 8.656). CONCLUSION: HGPIN on biopsy significantly predicts for contralateral lobe involvement and should be considered an exclusion criterion for focal therapy in prostate cancer patients. Patients with palpable tumor on digital rectal examination should be advised in favor of radical treatment as these patients may harbor more aggressive tumors involving the contralateral side despite the biopsy findings.

Anatomical retro-apical technique of synchronous (posterior and anterior) urethral transection: a novel approach for ameliorating apical margin positivity during robotic radical prostatectomy.

OBJECTIVE: To describe a novel synchronous approach to apical dissection during robotic-assisted radical prostatectomy (RARP) which augments circumferential visual appreciation of the prostatic apex and membranous urethra anatomy, and assess its effect on apical margin positivity. PATIENTS AND METHODS: Positive surgical margins (PSM) during RP predispose to earlier biochemical recurrence, and occur most frequently at the prostatic apex. Conventional apical transection after early ligation of the dorsal venous complex (DVC) remains suboptimal, as this approach obscures visualization of the intersection between prostatic apex and membranous urethra, leading to inadvertent apical capsulotomy and eventual margin positivity. A synchronous urethral transection commenced via a retro-apical approach was adopted in 209 consecutive patients undergoing RARP by one surgeon (A.T.) between April to September 2009. The apical margin rates for this group were compared with those of 1665 previous patients who received conventional urethral transection via an anterior approach after DVC ligation. Outcomes were adjusted for differences in clinicopathological variables. All RP specimens were processed according to institutional protocols, and examined by dedicated genitourinary pathologists. The location of PSMs was identified as apex, posterior, posterolateral, bladder neck, anterior, base, or multifocal. RESULTS: Patients receiving synchronous urethral transection had significantly lower apical PSM rates than the control group (1.4% vs 4.4%, P = 0.04). This marked improvement in the retro-apical group occurred despite a significantly higher incidence of aggressive cancer (≥ pT3a) documented on final specimen pathology (16% vs 10%, P = 0.027).Technical difficulty was encountered in three of 209 study patients, in whom urethral transection had to be completed using the classic anterior approach. CONCLUSION: Improved circumferential visualization of the prostatic apex, membranous urethra and their anatomical intersection facilitates precise dissection of the apex and its surrounding neural scaffold, and optimizes membranous urethral preservation. This has significantly ameliorated apical PSM rates in patients undergoing RARP, despite having to deal with more aggressive cancer on final specimen pathology.