Reasons for new MIS. Let's be fair: iTIND, Urolift and Rezum.

PURPOSE: To review and discuss the literature regarding iTIND, Urolift and Rezum and investigate the precise clinical indications of all three different approaches for their application in benign prostatic hyperplasia (BPH) treatment. MATERIALS AND METHODS: The PubMed-Medline and Cochrane Library databases were screened to identify recent English literature relevant to iTIND, Urolift and Rezum therapies. The surgical technique and clinical results for each approach were summarized narratively. RESULTS: iTIND, Urolift and Rezum are safe and effective minimally invasive procedures for the symptomatic relief of lower urinary tract symptoms (LUTS) due to BPH. iTIND requires the results of ongoing prospective studies, a long-term follow-up and a comparison against a reference technique to confirm the generalizability of the first pivotal study. Urolift provides symptomatic relief but the improvements are inferior to TURP at 24 months and long-term retreatments have not been evaluated. Rezum requires randomized controlled trials against a reference technique to confirm the first promising clinical results. However, clinical evidence from prospective clinical trials demonstrates the efficacy and safety of these procedures in patients with small- and medium-sized prostates. CONCLUSIONS: Although iTIND, Urolift, and Rezum cannot be applied to all bladder outlet obstruction (BOO) cases resulting from BPH, they provide a safe alternative for carefully selected patients who desire symptom relief and preservation of erectile and ejaculatory function without the potential morbidity of more invasive procedures.

Track and Teach: Identifying Key Movement Patterns in Endoscopic Transurethral Enucleation of the Prostate.

PURPOSE: We evaluated a system for noninvasive quantitative motion tracking to recognize differences in the movement pattern of experienced surgeons and beginners. Since performing endoscopic procedures requires extensive training, and tissue damage due to disruptive movements with sudden acceleration is possible, the learning curve for beginners is of clinical relevance. Steepening this curve may improve patient outcome. MATERIALS AND METHODS: We used a commercial gyroscope sensor with a wireless data link, which was attached to the resectoscope handle (RH). After recording, orientation was retrieved by application of the calculated rotation matrices to the RH vector relative to the sensor under the boundary condition of rotational movement around and quasi-constant distance to the pivot point at pelvic floor level. Data alignment, normalization, interpolation, and analysis were performed in custom software scripts. RESULTS: Experienced surgeons and beginners were recorded in n = 36 and n = 14 holmium laser enucleation of the prostate (HoLEP), respectively. Prostate size, patient age, and recorded procedure duration were comparable. Mean lever angle of the individual normalized motion patterns was considerably lower (19.28 ± 0.54° [SEM]) in the advanced than in the beginners' group (24.52 ± 1.00°; p = 0.0001). Further parameters such as velocity and motion variation demonstrated additional differences between both groups. CONCLUSIONS: We demonstrate the feasibility of motion tracking in HoLEP. Pronounced differences exist between different stages of surgeon experience with this procedure. The method can easily be adopted to aide young surgeons in resectoscope handling and identification of improvable motion patterns. Damage to the pelvic floor and surrounding tissue may thus be reduced.

"Three horse shoe-like incision" holmium laser enucleation of the prostate: first experience with a novel en bloc technique for anatomic transurethral prostatectomy.

OBJECTIVE: To demonstrate the performance of a novel holmium laser enucleation technique in patients with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Between September 2015 and August 2017, 114 consecutive patients underwent modified HoLEP [3 horse shoe-like incision HoLEP (3 HSI HoLEP)] for LUTS performed by an experienced urologist (A.M.). The surgical intervention and short postoperative course were analyzed. International Prostate Symptom Score (IPSS), quality of life score, maximum urinary flow rate (Q max), postvoid residual urine (PVR), and clinical and sociodemographic data were assessed preoperatively. The patient cohort was compared with existing data regarding clinical outcome parameters after surgical LUTS therapy. RESULTS: The mean size of the prostatic gland was 86.3 ± 46.5 mL. The mean total operative time was 49.6 min (15-280 min). IPSS, Q max, and PVR were 20.7, 10.8, and 112.7 mL, respectively, prior to the intervention in the 3 HSI HoLEP group. The complication rate for Clavien category-III complications was 4.4%; no category IV complications were recorded. Seven of 114 patients experienced urinary retention after catheter removal during the hospital stay. CONCLUSIONS: The presented procedure provides several improvements over the standard modality. The prostatic gland is enucleated en bloc in an anatomical manner without longitudinal incisions of the urethra. This method is fast, safe, and may be easier to learn. However, this is the first description recorded. Future multicenter, controlled studies should clarify the long-term outcomes and surgical performance of 3 HSI HoLEP.

Surgical therapy of prostatitis: a systematic review.

PURPOSE: The clinical term "prostatitis" refers to a clinical syndrome defined by the following 4 distinct entities: acute bacterial prostatitis (category 1), chronic bacterial prostatitis (category 2), chronic prostatitis/chronic pelvic pain syndrome (category 3), and asymptomatic prostatitis (category 4) The etiology of the chronic forms is still not fully understood and choice of therapy is often debated. The objective of this systematic review is to collect evidence on the surgical treatment of the chronic form of prostatitis and to evaluate its clinical implication. METHODS: We performed a systematic literature search and identified 6683 relevant publications, of which 16 were included in the review. RESULTS: Transurethral prostate resection was performed in 110 patients; 78 patients (70%) were reported as "cured", 16 patients (15%) as improved, and 16 patients (15%) as unchanged. Radical prostatectomy was performed in 21 patients; a full resolution of prostatitis related symptoms was reported for 20 patients (95%). No increased rates of complications or unusual complications were noted. CONCLUSIONS: Surgical therapy of chronic bacterial prostatitis or chronic pelvic pain syndrome might be a viable option; however, since little evidence is currently available and no randomized controlled trials have been conducted, the presently available data does not provide a base for clinical decisions.

Assessment of a course of realistic surgical training during medical education as a tool for pre-residential surgical training.

BACKGROUND: In recent years the focus on practical skills in the German curriculum of medical school has increased greatly. In this study we evaluate the value of a practical surgery course for medical students as a tool for surgical education, as a way of enhancing interest in surgical fields, and as a method of influencing medical students to subsequently choose a surgical career. METHODS: The "Feel like a surgeon"-course is an optional practical surgery course in which topographical anatomy and realistic surgical training using fresh human cadavers are combined for medical students of the RWTH Aachen University. Between 2010 and 2015 every student completed a survey before starting and after completing our course, and in 2015 a follow-up was performed. Using a standardized questionnaire, course quality, learning success and impact on post-instructional career and choice of profession was evaluated. RESULTS: In total, 82 students attended our course between 2010 and 2015 and took part in the evaluation. Evaluation of the course was positive overall, with an average grade of 1.4° ± °0.50. Significant improvement of basic, as well as more complex surgical skills and theoretical knowledge was noted. Furthermore, self-confidence for patient related assignments improved as well. In the follow-up evaluation, a high level of recommendation for surgical residents was seen, as was a high influence of the course on our students' career choice, although no significant change in career plans before and after taking the course was noted. CONCLUSIONS: Our results indicate that a practical surgical course can be a valuable tool to prepare students for a surgical residency and to improve their practical skills generally.

Influence of gentamicin-coded PVDF suture material on the healing of intestinal anastomosis in a rat model.

PURPOSE: Intestinal anastomosis is a fundamental procedure in general surgery and required to restore intestinal continuity following resection. The aim of this study was to evaluate whether a gentamicin-coated polyvinylidene fluoride (PVDF) suture material has beneficial effect on anastomotic healing. METHODS: Ninety Sprague-Dawley rats were divided into three groups: a PVDF-suture group, a gentamicin-coated PVDF (GPVDF)-suture group and a control group using Maxon® (polyglycolid-co-trimethylene carbonate). For each animal, a colonic anastomosis was performed. Ten animals from each group were sacrificed on postoperative days 3, 5, and 14. Measurements of anastomotic bursting pressure were performed on days 3 and 5. At each time, collagen type I/III ratio, MMP 2 and MMP-9 expression and the proliferation index (Ki67) were analyzed. RESULTS: In total, 90 animals underwent surgery without postoperative complications. Bursting strength in the GPVDF group was significantly elevated on day 5. Immunohistochemistry showed significant increase of the collagen type I/III ratio for PVDF and GPVDF on days 3 and 5. MMP2 was significantly increased for PVDF on days 3 and 5 and for GPVDF on day 5. The analysis of MMP9 revealed significant increase compared to control on day 3 and 5 (GPVDF) as well as on day 5 (PVDF). Staining for Ki67 revealed a significant elevation on postoperative day 3 for the PVDF and the GPVDF group. CONCLUSIONS: The present data shows the feasibility of PVDF as suture material for colonic anastomosis and confirms the ability of gentamicin to increase the stability of colonic anastomosis when used as coating material.

Proteomic analysis of the urothelial cancer landscape.

Urothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC. We evaluate sample-wise tumor specificity and rank biomarkers by target relevance. We identify robust proteomic subtypes with prognostic information independent from histopathological groups. In silico drug prediction suggests efficacy of several compounds hitherto not in clinical use. Both in silico and in vitro data indicate predictive value of the proteomic clusters for these drugs. We underline that proteomics is relevant for personalized oncology and provide abundance and tumor specificity data for a large part of the UC proteome ( www.cancerproteins.org ).

A systematic approach to mapping recessive disease genes in individuals from outbred populations.

The identification of recessive disease-causing genes by homozygosity mapping is often restricted by lack of suitable consanguineous families. To overcome these limitations, we apply homozygosity mapping to single affected individuals from outbred populations. In 72 individuals of 54 kindred ascertained worldwide with known homozygous mutations in 13 different recessive disease genes, we performed total genome homozygosity mapping using 250,000 SNP arrays. Likelihood ratio Z-scores (ZLR) were plotted across the genome to detect ZLR peaks that reflect segments of homozygosity by descent, which may harbor the mutated gene. In 93% of cases, the causative gene was positioned within a consistent ZLR peak of homozygosity. The number of peaks reflected the degree of inbreeding. We demonstrate that disease-causing homozygous mutations can be detected in single cases from outbred populations within a single ZLR peak of homozygosity as short as 2 Mb, containing an average of only 16 candidate genes. As many specialty clinics have access to cohorts of individuals from outbred populations, and as our approach will result in smaller genetic candidate regions, the new strategy of homozygosity mapping in single outbred individuals will strongly accelerate the discovery of novel recessive disease genes.

Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS).

BACKGROUND: Recessive mutations in the NPHS1 gene encoding nephrin account for approximately 40% of infants with congenital nephrotic syndrome (CNS). CNS is defined as steroid-resistant nephrotic syndrome (SRNS) within the first 90 days of life. Currently, more than 119 different mutations of NPHS1 have been published affecting most exons. METHODS: We here performed mutational analysis of NPHS1 in a worldwide cohort of 67 children from 62 different families with CNS. RESULTS: We found bi-allelic mutations in 36 of the 62 families (58%) confirming in a worldwide cohort that about one-half of CNS is caused by NPHS1 mutations. In 26 families, mutations were homozygous, and in 10, they were compound heterozygous. In an additional nine patients from eight families, only one heterozygous mutation was detected. We detected 37 different mutations. Nineteen of the 37 were novel mutations (approximately 51.4%), including 11 missense mutations, 4 splice-site mutations, 3 nonsense mutations and 1 small deletion. In an additional patient with later manifestation, we discovered two further novel mutations, including the first one affecting a glycosylation site of nephrin. CONCLUSIONS: Our data hereby expand the spectrum of known mutations by 17.6%. Surprisingly, out of the two siblings with the homozygous novel mutation L587R in NPHS1, only one developed nephrotic syndrome before the age of 90 days, while the other one did not manifest until the age of 2 years. Both siblings also unexpectedly experienced an episode of partial remission upon steroid treatment.

Adequate use of allele frequencies in Hispanics--a problem elucidated in nephrotic syndrome.

Previous studies in children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) in the USA have revealed inter-ethnic differences in their clinical presentation and outcome. However, ethnicity was based on self-identification rather than on molecular genetic data. Here, we show that genetic heterogeneity exists in self-identified Hispanic (Spanish-American) patients with steroid-resistant nephrotic syndrome (SRNS), as patients may be either of Caucasian or Mesoamerican (Native-American) genetic background. Twenty-one self-identified Hispanic patients with SRNS from 18 families were initially evaluated for mutations in the NPHS2 and WT1 genes. All patients resided and were cared for in the USA. We performed a total genome search for linkage in all Hispanic patients using 250K single nucleotide polymorphism microarrays, comparing Caucasian with Mesoamerican allele frequencies to determine regions of homozygosity by descent and to establish the correct allele frequency for each family. We found that only ten families (56%) of the 18 self-identified Hispanic families are genetically of Mesoamerican descent, whereas the other eight families (44%) are of Caucasian descent. Due to the small number of families examined, we were unable to draw any conclusion on the prevalence of NPHS2 and WT1 in this ethnic group, but the data do suggest that self-identification of ethnicity in Hispanic-American patients is not an adequate basis for genetic studies, as this cohort may represent not only patients of Mesoamerican origin but also patients of Caucasian origin. Thus, one needs to critically review previous studies of FSGS/SRNS patients that involved Hispanic patients as a group. Future larger studies may employ a total genome search for linkage to test self-identified Hispanic ethnicity for true Mesoamerican versus Caucasian ethnicity in order to generate valid genetic data.

Robotic waterjet wound debridement - Workflow adaption for clinical application and systematic evaluation of a novel technology.

OBJECTIVE: We evaluated the clinical potential of a novel robotic system for autonomous performance of waterjet wound debridement. SUMMARY BACKGROUND DATA: Within the last decade, waterjet wound debridement has proven to be a valid alternative to the conventional approach using sharp spoons and scalpel. METHODS: The DLR MIRO robot using the DLR MICA instrument for robotic surgery was adapted for actuation of an ERBEJET 2 flexible endoscopic waterjet probe. Waterjet debridement of various wound shapes and sizes using a porcine skin model was compared between this novel robotic system and a control group of human medical professionals with regard to wound area cleaned by the waterjet, off-target area, and procedural time. RESULTS: After the wound area was registered in the robotic system, it automatically generated a cleaning path and performed debridement based on generated surface model. While the robotic system demonstrated a significant advantage for the covered wound area (p = 0.031), the average off-target area was not significantly different from human controls. Human participants had high variability in cleaning quality across users and trials, while the robotic system provided stable results. Overall procedural time was significantly lower in trials performed by humans. CONCLUSIONS: Robotic waterjet wound debridement is a promising new technological approach compared to the current clinical standard of interventional wound therapy, providing higher efficiency and quality of wound cleaning compared to human performance. Additional trials on more complicated wound shapes and in vivo tissue are necessary to more thoroughly evaluate the clinical potential of this technology.

Robotic stone surgery - Current state and future prospects: A systematic review.

OBJECTIVE: To provide a comprehensive review of robot-assisted surgery in urolithiasis and to consider the future prospects of robotic approaches in stone surgery. MATERIALS AND METHODS: We performed a systematic PubMed© literature search using predefined Medical Subject Headings search terms to identify PubMed-listed clinical research studies on robotic stone surgery. All authors screened the results for eligibility and two independent reviewers performed the data extraction. RESULTS: The most common approach in robotic stone surgery is a robot-assisted pyelolithotomy using the da Vinci™ system (Intuitive Surgical Inc., Sunnyvale, CA, USA). Several studies show this technique to be comparable to classic laparoscopic and open surgical interventions. One study that focused on ureteric stones showed a similar result. In recent years, promising data on robotic intrarenal surgery have been reported (Roboflex Avicenna™; Elmed Medical Systems, Ankara, Turkey). Initial studies have shown its feasibility and high stone-free rates and prove that this novel endoscopic approach is safe for the patient and comfortable for the surgeon. CONCLUSIONS: The benefits of robotic devices in stone surgery in existing endourological, laparoscopic, and open treatment strategies still need elucidation. Although recent data are promising, more prospective randomised controlled studies are necessary to clarify the impact of this technique on patient safety and stone-free rates.

Algorithm-Based Motion Magnification for Video Processing in Urological Laparoscopy.

PURPOSE: Minimally invasive surgery is in constant further development and has replaced many conventional operative procedures. If vascular structure movement could be detected during these procedures, it could reduce the risk of vascular injury and conversion to open surgery. The recently proposed motion-amplifying algorithm, Eulerian Video Magnification (EVM), has been shown to substantially enhance minimal object changes in digitally recorded video that is barely perceptible to the human eye. We adapted and examined this technology for use in urological laparoscopy. MATERIALS AND METHODS: Video sequences of routine urological laparoscopic interventions were recorded and further processed using spatial decomposition and filtering algorithms. The freely available EVM algorithm was investigated for its usability in real-time processing. In addition, a new image processing technology, the CRS iimotion Motion Magnification (CRSMM) algorithm, was specifically adjusted for endoscopic requirements, applied, and validated by our working group. RESULTS: Using EVM, no significant motion enhancement could be detected without severe impairment of the image resolution, motion, and color presentation. The CRSMM algorithm significantly improved image quality in terms of motion enhancement. In particular, the pulsation of vascular structures could be displayed more accurately than in EVM. CONCLUSIONS: Motion magnification image processing technology has the potential for clinical importance as a video optimizing modality in endoscopic and laparoscopic surgery. Barely detectable (micro)movements can be visualized using this noninvasive marker-free method. Despite these optimistic results, the technology requires considerable further technical development and clinical tests.

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling.

Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured. While the disease mechanisms of NS are not well understood, genetic mapping studies suggest a multitude of unknown single-gene causes. We combined homozygosity mapping with whole-exome resequencing and identified an ARHGDIA mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA mutations (R120X and G173V) from individuals with SRNS abrogated interaction with RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA, indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS variant than RHOA. Moreover, the mutations enhanced migration of cultured human podocytes; however, enhanced migration was reversed by treatment with RAC1 inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia-associated defects. These findings identify a single-gene cause of NS and reveal that RHO GTPase signaling is a pathogenic mediator of SRNS.

COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness.

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme Q10 treatment. In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype. These data suggest that coenzyme Q10-related forms of SRNS and hearing loss can be molecularly identified and potentially treated.

Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations.

BACKGROUND AND OBJECTIVES: The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the genotype/phenotype correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion. RESULTS: Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years). CONCLUSIONS: (1) KTS mutations cause isolated NS with absence of WT in 46,XX females. (2) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. (3) KTS mutations cause NS with a slower progression when compared with missense mutations. (4) Missense mutations can occur with and without WT. (5) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis.