Friedrich-Carl von Rundstedt

Utility of patient-specific silicone renal models for planning and rehearsal of complex tumour resections prior to robot-assisted laparoscopic partial nephrectomy

To describe our experience using patient‐specific tissue‐like kidney models created with advanced three‐dimensional (3D)‐printing technology for preoperative planning and surgical rehearsal prior to robot‐assisted laparoscopic partial nephrectomy (RALPN).

New imaging techniques for nonmuscle invasive bladder cancer

Purpose of review Recent advances in imaging techniques provide innovative tools for the detection of bladder cancer. In patients with nonmuscle invasive cancer, there is a need for enhanced visualization of flat growing lesions and multifocal tumors. The aim of new imaging modalities is the improved detection and staging of bladder lesions, as an adjunct to conventional white light endoscopy. Recent findings Fluorescence cystoscopy with 5-aminolevulinic acid and hexaminolevulinate has been shown to improve the detection of papillary and flat bladder lesions in comparison to conventional white light cystoscopy. Prospective phase III clinical trials have demonstrated advanced diagnostic ability, enhanced tumor resection, and reduced tumor recurrence. Molecular targets for photodynamic diagnosis are currently under investigation. Narrow band imaging has gained in popularity because of its availability in both flexible and rigid cystoscopy and ureteroscopy and its potential for detection of carcinoma in situ. Emerging endomicroscopic technologies such as optical coherence tomography, confocal laser endomicroscopy, and Raman spectroscopy introduce real-time histologic imaging during the procedure. Summary While scientific evidence supports macroscopic applications, such as photodynamic diagnosis or narrow band imaging, and their progressive implementation in the clinical workflow, further studies are needed to identify the adjunct endomicroscopic technology optimal for enhanced accuracy and utility.

Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder.

BACKGROUND The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified. OBJECTIVE To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75). RESULTS AND LIMITATIONS UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study. CONCLUSIONS To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression. PATIENT SUMMARY Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.

Percent of Tracer Clearance at 40 Minutes in MAG3 Renal Scans Is More Sensitive Than T1/2 for Symptomatic Ureteropelvic Junction Obstruction

OBJECTIVE To increase the diagnostic sensitivity of standard MAG3 diuretic renal scans for ureteropelvic junction obstruction (UPJO) by exploring the utility of an alternative measurement P40, the percentage of maximal tracer counts present at 40 minutes. MATERIALS AND METHODS Patients with strong clinical and anatomic evidence for UPJO may have a normal T1/2, making definitive diagnosis difficult. We reviewed the charts of 142 consecutive patients who underwent successful laparoscopic or robotic-assisted laparoscopic pyeloplasty for UPJO between 2005 and 2015. Both pre- and postoperative renal scan images were available for 37 symptomatic patients with primary unilateral UPJO and 2 kidneys. We defined P40 as the percentage of maximal tracer counts present at 40 minutes. We identified the upper limit of normal (97.5th percentile, +2SD) for P40 using the preoperative renal scans from the unaffected kidney. We compared the sensitivity of P40 to T1/2 to identify symptomatic UPJO. RESULTS In our cohort, 51% of symptomatic patients (n = 19) had a normal T1/2 (median 8.9 minutes; interquartile range: 7.5 minutes) and 49% (n = 18) had an abnormal T1/2 (median: 40 minutes; interquartile range: 0 minute). None of the patients had an abnormal P40 on their unaffected kidney. All patients with an abnormal T1/2 also had an abnormal P40. P40 increased the sensitivity of the renal scan from 49% (n = 18 of 37) to 73% (n = 27 of 37) when compared to T1/2. The majority of patients (95%) demonstrated an improvement in P40 after pyeloplasty. CONCLUSION P40 markedly increases the sensitivity of a renal scan for diagnosing symptomatic UPJO and may be another valuable marker in addition to T1/2 to document functional improvement in drainage after pyeloplasty.

Current markers and their value in the era of immuno-oncology

Immunotherapy in urothelial cancer is a quickly evolving field as new agents are being investigated in multiple clinical trials and various clinical settings. The purpose of this review is to provide an insight into the mechanism of these treatments, potential targets to evaluate treatment response and to give an update on the current status of clinical trials. Urothelial cancer is a polyclonal disease with a substantial tumor heterogeneity and a high mutational load which may be beneficial as this may trigger a stronger T-cell mediated immune response. PD-1 expression has been shown to correlate with stage, grade, progression and poorer survival but it appears challenging to be utilized as a predictor for treatment response in urothelial cancer. Another important concept is immune cell (IC) infiltration, which is a reflection of the activated immune response within the target tissue. Marker genes may represent signaling pathways involved in T-cell recognition and lysis of T-cells. The complexity of the tumor and host interaction requires multiple concepts to be integrated into a future model to assess treatment response. We have evaluated multiple biomarker approaches currently investigated in clinical trials in urothelial cancer.

Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study.

Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30–40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall death were 3.2 (95% CI: 1.2 to 8.6) and 2.2 (95% CI: 1.1 to 4.4), respectively. On post-RC final pathology, 23 (46.9%) low-risk patients were up-classified to high risk and 17 (25.0%) high-risk patients were down-classified. Complete pathologic responses (pT0) were achieved in 7 (6.0%) patients and partial responses (pT1, pTa, pTis) were achieved in 28 (23.9%) patients. Of the 49 patients who did receive NAC, 43 (87.8%) received cisplatin-based and six (12.2%) received carboplatin-based regimens. Applying the MDACC model, we categorized 41 (83.7%) patients as high risk prior to NAC treatment. On final pathology, 3 (37.5%) low-risk patients were up-classified and 17 (41.5%) high-risk patients were down-classified. Complete pathologic responses (pT0) were seen in 13 (26.5%) patients and partial responses were seen in 10 (20.4%) patients. Although the utilization of NAC was not statistically significantly associated with CSS or OS (log-rank test p > 0.05 for both comparisons), it was associated with a 1.2 times increased odds (95% CI: 0.4 to 2.1) of post-RC reclassification from high to low risk on age-adjusted logistic regression. Conclusions: We found similar results using the clinical risk-stratification model in our cohort and showed that the high-risk category was associated with lower CSS and OS. NAC was associated with a higher probability of risk reclassification from high to low risk.

A modification of the embedding of tapered ileum in a continence mechanism as described previously: a self-critical analysis

The creation of a continent and reliably stable catheterizable valve is the most critical aspect in the construction of a continent cutaneous ileal reservoir and several techniques have been proposed. One of our techniques has been the application of a continence mechanism using serous-lined extramural valves as described previously by Abol-Enein and Ghoneim [1] for patients who were considered ineligible for orthotopic diversion. BJUI

Validation of a Simulation-training Model for Robotic Intracorporeal Bowel Anastomosis Using a Step-by-step Technique

OBJECTIVE To develop and validate a training model for the robotic intracorporeal bowel anastomosis. METHODS For simulation, surgeons with varying levels of experience were instructed about bowel anastomosis robotic surgical simulation in a short educational video. All participants performed the required steps for the intracorporeal bowel anastomosis under standardized conditions. The procedure consists of the following steps: division of the bowel with a stapler (1), incision and opening of the bowel limbs at the antimesenteric angle (2), insertion of the stapler into the 2 bowel limbs for the side-to-side anastomosis (3), and transverse closure of the anastomosis with the stapler (4). All simulations were performed using the daVinci SI robotic system. Face and content validity were assessed using a standardized questionnaire. Construct validity was evaluated using the Global Evaluative Assessment of Robotic Skills, a validated global performance rating scale. RESULTS Twenty-two surgeons participated including 6 robotic experts and 16 trainees. The expert participants rated the bowel anastomosis model highly for face validity (median 4/5; 64% agree or strongly agree), and all participants rated the content as a training model very highly (median 4.5/5; 100% agree or strongly agree). Discrimination between experts and trainees using Global Evaluative Assessment of Robotic Skills demonstrated construct validity (novice 17.6 vs expert 24.7, P = .03). CONCLUSION We demonstrate that the bowel anastomosis robotic surgical simulator is a reproducible and realistic simulation that allows for an objective skills assessment. We establish face, content, and construct validity for this model. This step-by-step technique may be utilized in training surgeons desiring to acquire skills in robotic intracorporeal urinary diversion.

Technique of Suprafascial Anastomosis With Reduced Risk of Stenosis of the Efferent Outlet in Continent Catheterizable Urinary Diversion

OBJECTIVE To describe our technique and long-term experience with a technique of a suprafascial anastomosis for the efferent continent segment in continent cutaneous urinary diversion, which aims to reduce the rate of stomal strictures. MATERIALS AND METHODS Between 1998 and 2013, up to 191 patients underwent continent cutaneous urinary diversion with a suprafascial anastomosis technique at our institution. A complete follow-up was achievable in 82 patients. The retrospective analysis included continence rates, stomal complications, and other complications related to the urinary diversion such as anastomotic insufficiencies, fistulas, or hernias. RESULTS The study population consisted of 82 patients with 67 (82%) women and 15 (18%) men with a median age of 58 years. The median length of follow-up was 82 months (range 13-203) with a median survival time of 46 (range 13-193) months. At the time of the analysis, 46 patients (57%) were still alive. Five out of 82 patients (6%) presented with a relevant stenosis in umbilical stoma that required surgical revisions. Nine patients (12%) with functional stenosis could be treated conservatively. Continence was achieved in 74 of 82 patients (90%). Only 8 patients reported some degree of incontinence. CONCLUSION The technique of a suprafascial stoma is a simple and safe technique that may help prevent the incidence of stomal complications.

A Review of Molecular Predictors of Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer

Locally advanced, muscle-invasive urothelial carcinoma of the bladder (MIBC) may be definitively treated with either radiotherapy or radical cystectomy (RC) with urinary diversion. Neoadjuvant chemotherapy (NAC) is typically administered prior to treatment with either modality. Receiving NAC prior to RC might confer a survival advantage compared to undergoing RC alone. However, its usefulness has been questioned due to concerns about over treatment and toxicity. Having the ability to predict whether individual patients would benefit from or be harmed by NAC would be an important tool in precision medicine. Unfortunately, to date no prognostic or predictive molecular markers have been validated for this purpose. In this manuscript, we review the current state of molecular markers in MIBC treatment and outline how recent advances in whole-genome sequencing may soon improve the selection of precisely targeted therapeutics for the benefit of individual patients.