Surgical gestures as a method to quantify surgical performance and predict patient outcomes.

How well a surgery is performed impacts a patient's outcomes; however, objective quantification of performance remains an unsolved challenge. Deconstructing a procedure into discrete instrument-tissue "gestures" is a emerging way to understand surgery. To establish this paradigm in a procedure where performance is the most important factor for patient outcomes, we identify 34,323 individual gestures performed in 80 nerve-sparing robot-assisted radical prostatectomies from two international medical centers. Gestures are classified into nine distinct dissection gestures (e.g., hot cut) and four supporting gestures (e.g., retraction). Our primary outcome is to identify factors impacting a patient's 1-year erectile function (EF) recovery after radical prostatectomy. We find that less use of hot cut and more use of peel/push are statistically associated with better chance of 1-year EF recovery. Our results also show interactions between surgeon experience and gesture types-similar gesture selection resulted in different EF recovery rates dependent on surgeon experience. To further validate this framework, two teams independently constructe distinct machine learning models using gesture sequences vs. traditional clinical features to predict 1-year EF. In both models, gesture sequences are able to better predict 1-year EF (Team 1: AUC 0.77, 95% CI 0.73-0.81; Team 2: AUC 0.68, 95% CI 0.66-0.70) than traditional clinical features (Team 1: AUC 0.69, 95% CI 0.65-0.73; Team 2: AUC 0.65, 95% CI 0.62-0.68). Our results suggest that gestures provide a granular method to objectively indicate surgical performance and outcomes. Application of this methodology to other surgeries may lead to discoveries on methods to improve surgery.

Two-year quality of life after robot-assisted radical prostatectomy according to pentafecta criteria and cancer of the prostate risk assessment (CAPRA-S).

The quality of life (QoL) of men with optimal outcomes after robot-assisted radical prostatectomy (RARP) is largely unexplored. Thus we assessed meaningful changes of QoL measured with the EORTC QLQ-C30 24 months after RARP according to postsurgical Cancer of the Prostate Risk Assessment score (CAPRA-S) and pentafecta criteria. 2871 prostate cancer (PCa) patients with completed EORTC QLQ-C30 were stratified according to CAPRA-S, pentafecta (erectile function recovery, urinary continence recovery, biochemical-recurrence-free survival (BFS), negative surgical margins) and 90-day Clavien-Dindo-complications (CDC) ≤ 3a. Multivariable logistic regression analyses (LRM) aimed to predict improvement of EORTC QoL. Mean preoperative QoL values did not significantly differ between CAPRA-S low- (LR) vs. high-risk (HR, 75.7 vs. 75.2; p = 0.7) and pentafecta vs. non-pentafecta groups (75.6 vs. 75.2; p = 0.6). After RARP, stable QoL rates for CAPRA-S LR vs. HR and pentafecta were 30, 26 and 30%, respectively. Corresponding improved QoL rates were 44, 32 and 47%. In LRM, CAPRA-S and pentafecta criteria were independent predictors of improved QoL. We conclude that most favourable combined outcomes after RARP might confer stable or even improved QoL but up to one third of patients might experience deterioration. This warrants further investigation how to capture the underlying cause and to address and potentially solve these perceived negative effects despite successful RARP.

The impact of age on pathological insignificant prostate cancer rates in contemporary robot-assisted prostatectomy patients despite active surveillance eligibility.

BACKGROUND: The aim of this study was to assess insignificant prostate cancer (iPCa) rates after robot-assisted radical prostatectomy (RARP) in contemporary patients who were preoperatively eligible for active surveillance (AS). iPCa indicates no risk of PCa progression. METHODS: We retrospectively analyzed 2837 RARP patients (2010-2019) who fulfilled at least one AS entry criteria set: Prostate Cancer Research International - Active Surveillance (PRIAS), University of California San Francisco (UCSF) (San Francisco, CA, USA), National Comprehensive Cancer Network (NCCN) or University of Toronto, ON, Canada. We utilized four different iPCa definitions: 1) based on pT2 and Gleason Score ≤6 and also cumulative tumor-volume; 2) ≤2.5mL; 3) ≤0.7mL; or 4) ≤0.5mL. For each AS set we tested the rates of iPCa and compared between age <70 vs. ≥70 years. This was complemented by multivariable logistic regression (LRM) predicting iPCa, adjusted for age and clinical AS variables. Finally, within the subgroup who had iPCa, we tested the rate of those who were deemed preoperatively AS ineligible. RESULTS: Between most (PRIAS) and least stringent (TORONTO) AS sets, iPCa was correctly predicted in 70-57%. Similarly, for iPCa definitions 2-4, rates were 59-42%, 34-19% and 27-14%. Senior patients harbored decreased proportions of iPCa. LRM confirmed that advanced age is associated with a lower chance of iPCa. More stringent AS sets lead to higher rates of AS ineligibility, e.g. 53% for PRIAS, despite iPCa. CONCLUSIONS: AS sets show limited accuracy for stricter iPCa definitions, which further declined with advanced age. Greater AS stringency resulted in more AS ineligible patients despite harboring iPCa. In consequence, patients are at risk for overtreatment. Clinicians must consider age and different AS sets that result in highly variable detection rates of iPCa.

Improvement of quality of life and symptom burden after robot-assisted radical prostatectomy in patients with moderate to severe LUTS.

The aim of this study was to assess clinically meaningful differences of preoperative lower urinary tract symptoms (LUTS) and quality of life (QoL) before and after robot-assisted radical prostatectomy (RARP). Therefore we identified 5506 RARP patients from 2007 to 2018 with completed International Prostate Symptom Score (IPSS) and -QoL questionnaires before and 12 months after RARP in our institution. Marked clinically important difference (MCID) was defined by using the strictest IPSS-difference of - 8 points. Multivariable logistic regression analyses (LRM) aimed to predict ∆IPSS ≤ - 8 and were restricted to RARP patients with preoperatively moderate (IPSS 8-19) vs. severe (IPSS 20-35) LUTS burden (n = 2305). Preoperative LUTS was categorized as moderate and severe in 37% (n = 2014) and 5.3% of the complete cohort (n = 291), respectively. Here, a postoperative ∆IPSS ≤ - 8, was reported in 38% vs. 90%. In LRM, younger age (OR 0.98, 95%CI 0.97-0.99; p = 0.007), lower BMI (OR 0.94, 95%CI 0.92-0.97; p < 0.001), higher preoperative LUTS burden (severe vs. moderate [REF.] OR 15.6, 95%CI 10.4-23.4; p < 0.001), greater prostate specimen weight (per 10 g, OR 1.12, 95%CI 1.07-1.16; p < 0.001) and the event of urinary continence recovery (OR 1.66 95%CI 1.25-2.21; p < 0.001) were independent predictors of a marked LUTS improvement after RARP. Less rigorous IPSS-difference of - 5 points yielded identical predictors. To sum up, in substantial proportions of patients with preoperative moderate or severe LUTS a marked improvement of LUTS and QoL can be expected at 12 months after RARP. LRM revealed greatest benefit in those patients with preoperatively greatest LUTS burden, prostate enlargement, lower BMI, younger age and the event of urinary continence recovery.

Superior early and long-term continence following early micturition on day 2 after robot-assisted radical prostatectomy: a randomized prospective trial.

PURPOSE: To elucidate early and long-term continence and patient comfort depending on type and duration of catheterization after robot-assisted radical prostatectomy. METHODS: 198 patients were randomized prospectively into three groups (May 2016-July 2017): A transurethral catheter with micturition on postoperative day (POD) 5 was placed in the control group (TD5); a suprapubic tube (SPT) with micturition on POD 5 was placed in the group SD5 or with micturition on POD 2 in group SD2, respectively. Questionnaires were used for catheter-related satisfaction. Functional outcome analysis included residual volume analysis, uroflowmetry, IPSS, 12-h pad test, and daily pad use. Follow-up was conducted up to 12 months. RESULTS: Postoperative comfort and catheter-related complications were similar in the three groups. However, on the day of catheter removal, continence was significantly better in the 12-h pad test for the SD2 group with 14 ml vs. 30 ml (TD5) and 24 ml (SD5), p = 0.007. Median residual urine volume between the groups was comparable with 17 ml in TD5, 7 ml in SD5, and 11 ml in SD2, (p = 0.07). Postoperative IPSS did not differ significantly in the follow-up period. After 4 weeks, 63% of the patients in SD2 were continent (no pad/day) compared to 33% in TD5 and 41% in SD5, p = 0.004. After 12 months, 76% were continent in TD5, 87% in SD5, and 94% in SD2, p = 0.023. CONCLUSIONS: Early micturition after SPT placement in robotic radical prostatectomy seems to be beneficial without an increased risk of complications.

Comprehensive Decongestive Therapy as a Treatment for Secondary Lymphedema of the Lower Extremity and Quality of Life of Women After Gynecological Cancer Surgery.

BACKGROUND Lymphedema is a clinical manifestation of lymphatic system failure, caused by an imbalance between the transport capacity of the lymphatic system and the volume of the produced lymph. Lymphedema is complication and significantly worsens quality of life (QoL). MATERIAL AND METHODS There were 50 patients diagnosed with secondary lymphedema of the lower extremities after gynecological cancer followed by radiotherapy included in this study. The average age was 57.76 years (standard deviation±10.08). Patients were treated at the Department of Physiotherapy, Balneology and Medical Rehabilitation, in hospital NsP in Bardejov. During therapy, we applied manual lymphatic drainage, instrumental lymphatic drainage, multilayer bandage, vascular gymnastics (with loaded external compression), hydrotherapy, and patient education on the adjustment necessary for a life-long regimen. The circumference of the limb was measured using the Kuhnkes disk method, QoL was assessed using the LYMQOL LEG questionnaire, and for assessment of pain the Visual Analogue Scale (VAS) was used. RESULTS After treatment, we found a reduction in lymphedema (P<0.001), an increase in QoL (P<0.001), and a reduction in pain (P<0.001). We found a significant relationship between QoL change and pain in the domains of symptoms, function, and overall QoL (P<0.005). The results showed that reduction of lymphedema was not a significant predictor of QoL (P>0.001). CONCLUSIONS We found a positive effect in the treatment of secondary lymphedema of the lower extremity on the QoL of women after uterine cancer surgery, and also found that reduction of lymphedema and age were not predictors of improvement in QoL.

Temporal and dynamic changes in plantar pressure distribution, as well as in posture during slow walking in flat and high-heel shoes.

PURPOSE: The aim of the study was to assess the differences in plantar pressure distribution and in posture during slow and very slow walking on the treadmill in flat and high-heeled shoes. METHODS: The Pedar-X® (Novel, Munich, Germany) measuring insoles were used to measure the plantar pressure distribution and to assess temporal parameters during walking on the treadmill with the speed v1 = 0.97 ms-1 and v2 = 0.56 ms-1 in flat shoes (FS) and HH. For postural measurement, the SonoSens Monitor Analyzer (Gefremed, Chemnitz, Germany) was used. Thirty healthy females who only occasionally wear HH volunteered to participate in the study (age: 21.8 ± 2.09 years, weight: 55.7 ± 4.05 kg, height: 1.66 ± 0.03 m). For statistical analysis the ANOVA, and paired t-test were used. RESULTS: Significant differences in walking in HH were detected in temporal and plantar pressure variables, compared to FS. The walking speed influenced the temporal variables, but not the measured dynamic parameters, in either shoes. In the sagittal plane, significant differences in all sections of the spine were identified for v1 and v2. While walking in HH, lordosis at lumbar spine decreased significantly as well as at cervical spine, and kyphosis increased in the thoracic spine. In HH statistically significant differences between the walking speeds were observed particularly in the thoracic spine. CONCLUSIONS: Walking in high heels caused a plantar pressure changes and curvature of the spine, and the slowing of walking speed did not prevent these changes.

Fluorescence-supported lymphography and extended pelvic lymph node dissection in robot-assisted radical prostatectomy: a prospective, randomized trial.

PURPOSE: To demonstrate the benefits of fluorescence-supported extended pelvic lymph node dissection (ePLND) compared to regular ePLND in robot-assisted radical prostatectomy. METHODS: 120 patients with intermediate- or high-risk prostate cancer were prospectively randomized (1:1): in the intervention group, indocyanine green (ICG) was injected transrectally into the prostate before docking of the robot. In both groups, ePLND was performed including additional dissection of fluorescent lymph nodes (LN) in the ICG group. RESULTS: After drop-out of two patients, 59 patients were allocated to the control (A) and intervention group (B) with a median PSA of 8,6 ng/ml. Median console time was 159 (A) vs. 168 (B) min (p = 0.20) with a longer time for ICG-ePLND: 43 (A) vs. 55 min (B) (p = 0.001). 2609 LN were found with significantly more LN after ICG-supported ePLND with a median of 25 vs. 17 LN in A (p < 0.001). Nodal metastases were detected in 6 patients in A (25 cancerous LN) vs. 9 patients in B (62 positive LN) (p = 0.40). In seven of nine patients, ICG-ePLND identified at least one cancer-positive LN (sensitivity 78%), 27 of 62 cancerous LN were fluorescent. Symptomatic lymphocele occurred in one patient in a and in three patients in b (p = 0.62). After a median follow-up of 22.9 months, PSA levels were similar. CONCLUSIONS: While ICG-ePLND seems to be beneficial for a better understanding of the lymphatic drainage and a more meticulous diagnostic approach, the sensitivity is not sufficient to recommend stand-alone ICG lymph node dissection.

Postoperative patient comfort in suprapubic drainage versus transurethral catheterization following robot-assisted radical prostatectomy: a prospective randomized clinical trial.

PURPOSE: To evaluate the impact of the type of urinary diversion (suprapubic vs. transurethral catheterization) on patients' postoperative pain after radical prostatectomy, development of bacteriuria and long-term functional results. METHODS: A randomized, prospective clinical trial was performed including 160 patients who underwent robot-assisted radical prostatectomy after randomization into two groups: intraoperatively, a transurethral catheter (control group) or an additional suprapubic tube (with removal of the transurethral catheter in the morning of postoperative day 1; intervention group) was placed. Primary study endpoint was postoperative pain objectified by the numeric rating scale questionnaire. Secondary endpoints were bacteriuria after catheter removal and functional outcomes after up to 2 years of follow-up. RESULTS: There were no significant differences in demographic and perioperative data. Starting on postoperative day 2, patients in the suprapubic diversion group had significantly less pain on every time point preceding the removal of the catheter compared to the control cohort with a median overall numeric rating score on postoperative day 1-4 of 2.4 points in the transurethral versus 1.3 in the intervention group (p = 0.012). No statistical difference was found in postoperative bacteriuria and complications as well as in functional results, quality of life and incontinence rates after a median follow-up of 22 months. CONCLUSIONS: Suprapubic drainage in robot-assisted radical prostatectomy shows significantly decreased pain levels during the catheterization period compared to the transurethral diversion without compromising long-term functional results. Intraoperative placement of a suprapubic tube should be discussed as a standard procedure for further improvement of patients' postoperative comfort.

Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?

It has been reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR) besides transcellular chloride transport, also controls the paracellular permeability of bronchial epithelium. The aim of this study was to test whether overexpressing wtCFTR solely regulates paracellular permeability of cell monolayers. To answer this question we used a CFBE41o- cell line transfected with wtCFTR or mutant F508del-CFTR and compered them with parental line and healthy 16HBE14o- cells. Transepithelial electrical resistance (TER) and paracellular fluorescein flux were measured under control and CFTR-stimulating conditions. CFTR stimulation significant decreased TER in 16HBE14o- and also in CFBE41o- cells transfected with wtCFTR. In contrast, TER increased upon stimulation in CFBE41o- cells and CFBE41o- cells transfected with F508del-CFTR. Under non-stimulated conditions, all four cell lines had similar paracellular fluorescein flux. Stimulation increased only the paracellular permeability of the 16HBE14o- cell monolayers. We observed that 16HBE14o- cells were significantly smaller and showed a different structure of cell-cell contacts than CFBE41o- and its overexpressing clones. Consequently, 16HBE14o- cells have about 80% more cell-cell contacts through which electrical current and solutes can leak. Also tight junction protein composition is different in 'healthy' 16HBE14o- cells compared to 'cystic fibrosis' CFBE41o- cells. We found that claudin-3 expression was considerably stronger in 16HBE14o- cells than in the three CFBE41o- cell clones and thus independent of the presence of functional CFTR. Together, CFBE41o- cell line transfection with wtCFTR modifies transcellular conductance, but not the paracellular permeability. We conclude that CFTR overexpression is not sufficient to fully reconstitute transport in CF bronchial epithelium. Hence, it is not recommended to use those cell lines to study CFTR-dependent epithelial transport.

Paracellular permeability of bronchial epithelium is controlled by CFTR.

In normal airway epithelium, the cystic fibrosis transmembrane conductance regulator (CFTR) transports Cl(-) ions to the apical surface of the epithelium paralleled by the flow of water through transcellular and paracellular pathways. The hypothesis was tested whether CFTR not only regulates the transcellular but also the paracellular shunt pathway. Therefore, we performed measurements of transepithelial electrical resistance (TER) and paracellular (14)C-mannitol permeability in wtCFTR (16HBE14o(-)) and delF508-CFTR (CFBE41o(-)) expressing human bronchial epithelial cells. Under resting conditions, CFBE41o(-) cell monolayers exhibit a higher paracellular permeability and lower TER as compared to 16HBE14o(-) monolayers. Stimulation of CFTR by cAMP induces opposite effects in the two cell lines. 16HBE14o(-) monolayers show a sharp decrease of TER, in parallel with a concomitant increase of paracellular permeability. The change in paracellular permeability is mediated by a myosin II dependent mechanism because it can be blocked by the myosin light chain kinase inhibitor ML-7. In contrast, CFBE41o(-) cells respond to cAMP stimulation with a decrease of paracellular permeability, paralleled by slight increase of TER. We conclude that stimulation of wtCFTR increases vectorial transcellular salt transport and, simultaneously, the paracellular permeability allowing water to follow through the paracellular pathway. In contrast, in CF epithelium cAMP stimulation increases neither vectorial salt transport nor paracellular permeability which is likely to contribute to the CF pulmonary phenotype. Taken together, our results link CFTR dysfunction to an improper regulation of the paracellular transport route.

C-reactive protein makes human endothelium stiff and tight.

Elevation of C-reactive protein (CRP) in human blood accompanies inflammatory processes, including cardiovascular diseases. There is increasing evidence that the acute-phase reactant CRP is not only a passive marker protein for systemic inflammation but also affects the vascular system. Further, CRP is an independent risk factor for atherosclerosis and the development of hypertension. Another crucial player in atherosclerotic processes is the mineralocorticoid hormone aldosterone. Even in low physiological concentrations, it stimulates the expression and membrane insertion of the epithelial sodium channel, thereby increasing the mechanical stiffness of endothelial cells. This contributes to the progression of endothelial dysfunction. In the present study, the hypothesis was tested that the acute application of CRP (25 mg/L), in presence of aldosterone (0.5 nmol/L; 24 hour incubation), modifies the mechanical stiffness and permeability of the endothelium. We found that endothelial cells stiffen in response to CRP. In parallel, endothelial epithelial sodium channel is inserted into the plasma membrane, while, surprisingly, the endothelial permeability decreases. CRP actions are prevented either by the inhibition of the intracellular aldosterone receptors using spironolactone (5 nmol/L) or by the inactivation of epithelial sodium channel using specific blockers. In contrast, inhibition of the release of the vasodilating gas nitric oxide via blockade of the phosphoinositide 3-kinase/Akt pathway has no effect on the CRP-induced stiffening of endothelial cells. The data indicate that CRP enhances the effects of aldosterone on the mechanical properties of the endothelium. Thus, CRP could counteract any decrease in arterial blood pressure that accompanies severe acute inflammatory processes.

Real-time monitoring of cell elasticity reveals oscillating myosin activity.

The cytoskeleton is the physical and biochemical interface for a large variety of cellular processes. Its complex regulation machinery is involved upstream and downstream in various signaling pathways. The cytoskeleton determines the mechanical properties of a cell. Thus, cell elasticity could serve as a parameter reflecting the behavior of the system rather than reflecting the specific properties of isolated components. In this study, we used atomic force microscopy to perform real-time monitoring of cell elasticity unveiling cytoskeletal dynamics of living bronchial epithelial cells. In resting cells, we found a periodic activity of the cytoskeleton. Amplitude and frequency of this spontaneous oscillation were strongly affected by intracellular calcium. Experiments reveal that basal cell elasticity and superimposed elasticity oscillations are caused by the collective action of myosin motor proteins. We characterized the cell as a mechanically multilayered structure, and followed cytoskeletal dynamics in the different layers with high time resolution. In conclusion, the collective activities of the myosin motor proteins define overall mechanical cell dynamics, reflecting specific changes of the chemical and mechanical environment.