Objective
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).
Patients and Methods
A feasibility study of 10 patients with solid renal masses who underwent RALPN after preoperative rehearsal using 3D‐print kidney models. A single surgeon performed all surgical rehearsals and procedures. Using standard preoperative imaging and 3D reconstruction, we generated pre‐surgical models using a silicone‐based material. All surgical rehearsals were performed using the da Vinci® robotic system (Intuitive Surgical Inc., Sunnyvale, CA, USA) before the actual procedure. To determine construct validity, we compared resection times between the model and actual tumour in a patient‐specific manner. Using 3D laser scanning in the operating room, we quantified and compared the shape and tumour volume resected for each model and patient tumour.
Results
We generated patient‐specific models for 10 patients with complex tumour anatomy. R.E.N.A.L. nephrometry scores were between 7 and 11, with a mean maximal tumour diameter of 40.6 mm. The mean resection times between model and patient (6:58 vs 8:22 min, P = 0.162) and tumour volumes between the computer model, excised model, and excised tumour (38.88 vs 38.50 vs 41.79 mm3, P = 0.98) were not significantly different.
Conclusions
We have developed a patient‐specific pre‐surgical simulation protocol for RALPN. We demonstrated construct validity and provided accurate representation of enucleation time and resected tissue volume. This simulation platform can assist in surgical decision‐making, provide preoperative rehearsals, and improve surgical training.
Objectives
Most renal tumours can be treated with a partial nephrectomy, with robot‐assisted partial nephrectomy becoming the new gold standard. This procedure is challenging to learn in a live ...setting, especially the enucleation and renorraphy phases. In this study, we attempted to evaluate face, content, and preliminary construct validity of a 3D‐printed silicone renal tumour model in robotic training for robot‐assisted partial nephrectomy.
Materials and Methods
We compared the operative results of three groups of surgeons with different experience levels (>20 partial nephrectomies, 1–20 partial nephrectomies and no experience at all) performing a robotic tumour excision of a newly developed silicone model with four embedded 3D‐printed renal tumours. We evaluated the participants' performance using surgical margins, excision time, total preserved parenchyma, tumour injury and GEARS score (as assessed by two blinded experts) for construct validity. Postoperatively, the participants were asked to complete a survey to evaluate the usefulness, realism and difficulty of the model as a training and/or evaluation model. NASA‐TLX scores were used to evaluate the operative workload.
Results
Thirty‐six participants were recruited, each group consisting of 10–14 participants. The operative performance was significantly better in the expert group as compared to the beginner group. NASA‐TLX scores proved the model to be of an acceptable difficulty level.
Expert group survey results showed an average score of 6.3/10 on realism of the model, 8.2/10 on the usefulness as training model and 6.9/10 score on the usefulness as an evaluation tool. GEARS scores showed a non‐significant tendency to improve between trials, emphasizing its potential as a training model.
Conclusion
Face and content validity of our 3D renal tumour model were demonstrated. The vast majority of participants found the model realistic and useful for training and for evaluation. To evaluate construct and predictive validity, we require further research, aiming to compare the results of 3D‐model trained surgeons with those of untrained surgeons in real‐life surgery.
Advanced Bladder Cancer (BLCA) remains a clinical challenge that lacks effective therapeutic measures. Here, we show that distinct, stage-wise metabolic alterations in BLCA are associated with the ...loss of function of aldehyde oxidase (AOX1). AOX1 associated metabolites have a high predictive value for advanced BLCA and our findings demonstrate that AOX1 is epigenetically silenced during BLCA progression by the methyltransferase activity of EZH2. Knockdown (KD) of AOX1 in normal bladder epithelial cells re-wires the tryptophan-kynurenine pathway resulting in elevated NADP levels which may increase metabolic flux through the pentose phosphate (PPP) pathway, enabling increased nucleotide synthesis, and promoting cell invasion. Inhibition of NADP synthesis rescues the metabolic effects of AOX1 KD. Ectopic AOX1 expression decreases NADP production, PPP flux and nucleotide synthesis, while decreasing invasion in cell line models and suppressing growth in tumor xenografts. Further gain and loss of AOX1 confirm the EZH2-dependent activation, metabolic deregulation, and tumor growth in BLCA. Our findings highlight the therapeutic potential of AOX1 and provide a basis for the development of prognostic markers for advanced BLCA.
Reliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic ...stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213–231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.
Objectives
To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ‐confined, node‐negative urothelial cancer of the bladder (UCB) in a post hoc analysis of ...a prospective clinical trial. To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumours exhibited LVI.
Patients and Methods
Surgical and tumour factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1–T2 N0 UCB in the p53‐MVAC trial (Southwest Oncology Group 4B951/NCT00005047). The presence or absence of LVI was determined by pathological examination of transurethral resection or RC specimens. Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS).
Results
Among 499 patients with a median follow‐up of 4.9 years, a subset of 102 (20%) had LVI‐positive tumours. Of these, 34 patients had pT1 and 68 had pT2 disease. LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 95% confidence interval (CI) 1.15–2.77; number of events (EV) 95; P = 0.01) and with OS with a HR of 2.02 (95% CI 1.31–3.11; EV 98; P = 0.001) after adjustment for pathological stage. Among 27 patients with LVI‐positive tumours who were randomised to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70, 95% CI 0.16–3.17; EV 7; P = 0.65) or with OS (HR 0.45, 95% CI 0.11–1.83; EV 9; P = 0.26).
Conclusions
Our post hoc analysis of the p53‐MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1–T2N0 disease. The analysis did not show a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not excluded.
We present a detailed procedure for the robotic-assisted plate osteosynthesis of an anterior acetabular fracture. The purpose of this work was to describe a robotic-assisted minimally invasive ...technique as a possible method for reducing complications, pain, and hospitalization. Another goal was to present technical recommendations and to assess potential pitfalls and problems of the new surgical approach.
Surgery was performed in an interdisciplinary setting by an experienced orthopedic surgeon and a urologist. The DaVinci System with standard instruments was used. Reduction was achieved through indirect traction of a pin that was introduced into the femoral neck and direct manipulation via the plate. The plate position and fixation were achieved through 7 additional minimally invasive incisions.
The technique has multiple advantages, such as no detachment of the rectus abdominal muscle, a small skin incision, and minimal blood loss. Furthermore, this approach might lower the incidence of hernia formation, infection, and postoperative pain.
We see the presented technique as a demanding yet progressive and innovative surgical method for treating acetabular fractures with indications for anterior plate fixation.
The study was approved by the local institutional review board (Nr. 248/18).
We evaluated the hydrostatic pressure of the renal pelvis (RPP) as a radiation-free alternative to fluoroscopic nephrostogram to assess ureteral patency after percutaneous nephrolithotomy (PCNL).
...Retrospective non-inferiority study analyzing 248 PCNL-patients (86 female (35%) and 162 males (65%)) between 2007 and 2015. Postoperatively, RPP was measured using a central venous pressure manometer in cmH
O. The primary endpoint was to assess RPP depending on the patency of the ureter and the nephrostomy tube removal. Secondary, the upper limit of normal RPP of Formula: see text 20 cmH
O was assessed as an indicator of an unobstructed patency.
The median procedure duration was 141 min (112-171.5) with a stone free rate of 82% (n = 202). RPP was significantly higher in patients with obstructive nephrostogram with 25.0 mmH
O (21.0-32.0) versus 20.0 mmH
O (16.0-24.0; p < 0.001). The pressure was lower in successful nephrostomy removal with 18 cmH
O (15-21) versus 23 cmH
O (20-29) in the leakage group (p < 0.001). The analysis of a cut-off of Formula: see text 20 cmH
O showed a sensitivity of 76.9% (95% CI 60.7%; 88.9%) and a specificity of 61.5% (95% CI 54.6%; 68.2%). The negative predictive value was 93.4% (95% CI: 87.9%; 97.0%) and the positive predictive value 27.3% (95% CI 19.2%; 36.6%). The accuracy of the model showed an AUC = 0.795 (95% CI 0.668; 0.862).
The hydrostatic RPP seems to allow a bedside evaluation of ureteral patency after PCNL.
Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize ...age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62–71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.
To evaluate clinical outcomes and possible MR imaging predictors of clinical success after prostatic artery embolization (PAE) with 250-μm hydrogel particles.
During a span of 1.5 years, 30 patients ...with moderate to severe lower urinary tract symptoms were included in a prospective, nonrandomized study. Embolization of at least one prostatic artery was considered as technical success. International Prostate Symptom Score (IPSS), quality of life (QOL), peak urinary flow rate (Q
), residual urine volume, prostate volume, prostate-specific antigen level, and International Index of Erectile Function (IIEF) were recorded at baseline and at 1, 3, and 6 months after PAE. Multiparametric MR imaging was performed before PAE (n = 25) and 1 day (n = 25), 1 month (n = 7), 3 months (n = 7), and 6 months (n = 22) after intervention. A Wilcoxon-Mann-Whitney test was used to assess changes over time, and Spearman rank-correlation coefficient was used for outcome prediction.
PAE was technically successful in 90% of patients (n = 27). Clinical success (IPSS < 18 with decrease > 25% and QOL score < 4 with decrease ≥ 1 or Q
≥ 15 mL/s and increase of ≥ 3.0 mL/s) rates were 59% (16 of 27), 63% (17 of 27), and 74% (20 of 27) after 1, 3, and 6 mo, respectively. IIEF scores did not differ significantly during follow-up. The following adverse events occurred after PAE: urethral burning (5 of 27), fever (2 of 27), and urethral bleeding, rectal bleeding, cystitis, and penile burning sensation (1 of 27 each). No statistical correlations between initial multiparametric MR imaging changes and clinical parameters after 6 months were found (P values from .14 to .98).
PAE with 250-μm hydrogel microspheres led to good clinical success after 6 months with a low complication rate. Significant MR imaging predictors of clinical success were not identified.