Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Comparison of anatomically informed class solution template trajectories with patient-specific trajectories for stereotactic radiosurgery and radiotherapy.

Class solution template trajectories are used clinically for efficiency, safety, and reproducibility. The aim was to develop class solutions for single cranial metastases radiotherapy/radiosurgery based on intracranial target positioning and compare to patient-specific trajectories in the context of 4π optimization. Template trajectories were constructed based on the open-source Montreal Neurological Institute (MNI) average brain. The MNI brain was populated with evenly spaced spherical target volumes (2 cm diameter, N = 243) and organs-at-risk (OARs) were identified. Template trajectories were generated for six anatomical regions (frontal, medial, and posterior, each with laterality dependence) based on previously published 4π optimization methods. Volumetric modulated arc therapy (VMAT) treatment plans generated using anatomically informed template 4π trajectories and patientspecific 4π trajectories were compared against VMAT plans from a standard four-arc template. Four-arc optimization techniques were compared to the standard VMAT template by placing three spherical targets in each of six anatomical regions of a test patient. This yielded 54 plans to compare various plan quality metrics. Increasing plan technique complexity, the total number of OAR maximum dose reductions compared to the standard arc template for the 6 anatomical classes was 4+/-2 (OFIXEDc) and 7+/-2 (OFIXEDi). In 65.6% of all cases, optimized fixed-couch positions outperformed the standard-arc template. Of the three comparisons, the most complex (OFIXEDi) showed the greatest statistical significance compared to the least complex (VMATi) across 12 plan quality metrics of maximum dose to each OAR, V12Gy, total plan Monitor Units, conformity index, and gradient index (p < 0.00417). In approximately 70% of all cases, 4π optimization methods outperformed the standard-arc template in terms of maximum dose reduction to OAR, by exclusively changing the arc geometry. We conclude that a tradeoff exists between complexity of a class solution methodology compared to patient-specific methods for arc selection, in the context of plan quality improvement.

Patient-specific collision zones for 4π trajectory optimized radiation therapy.

PURPOSE: The 4π methodology determines optimized noncoplanar subarcs for stereotactic radiation therapy that minimize dose to organs-at-risk. Every combination of treatment angle is examined, but some angles are not appropriate as a collision would occur between the gantry and the couch or the gantry and the patient. Those combinations of couch and gantry angles are referred to as collision zones. A major barrier to applying 4π to stereotactic body radiation therapy (SBRT) is the unknown shape of the collision zones, which are significant as patients take up a large volume within the 4π sphere. This study presents a system that determines patient-specific collision zones, without additional clinical steps, to enable safe and deliverable noncoplanar treatment trajectories for SBRT patients. METHODS: To augment patient's computed tomography (CT) scan, full body scans of patients in treatment position were acquired using an optical scanner. A library of a priori scans (N = 25) was created. Based on the patients' treatment position and their body dimensions, a library scan is selected and registered to the CT scan of the patient. Next, a model of the couch and immobilization equipment is added to the patient model. This results in a patient model that is then aligned with a model of the treatment LINAC in a "virtual treatment room," where both components can be rotated to test for collisions. To test the collision detection algorithm, an end-to-end test was performed using a cranial phantom. The registration algorithm was tested by comparing the registered patient collision zones to those generated by using the patient's matching scan. RESULTS: The collision detection algorithm was found to have a 97.80% accuracy, a 99.99% sensitivity, and a 99.99% negative predictive value (NPV). Analysis of the registration algorithm determined that a 6 cm buffer was required to achieve a 99.65% mean sensitivity, where a sensitivity of unity is considered to be a requirement for safe treatment delivery. With a 6 cm buffer, the mean accuracy was 86.70% and the mean NPV was 99.33%. CONCLUSIONS: Our method of determining patient-specific collision zones can be accomplished with minimal user intervention based on an a priori library of body surface scans, thus enabling the safe application of 4π SBRT.

Population genomics of Drosophila suzukii reveal longitudinal population structure and signals of migrations in and out of the continental United States.

Drosophila suzukii, or spotted-wing drosophila, is now an established pest in many parts of the world, causing significant damage to numerous fruit crop industries. Native to East Asia, D. suzukii infestations started in the United States a decade ago, occupying a wide range of climates. To better understand invasion ecology of this pest, knowledge of past migration events, population structure, and genetic diversity is needed. In this study, we sequenced whole genomes of 237 individual flies collected across the continental United States, as well as several sites in Europe, Brazil, and Asia, to identify and analyze hundreds of thousands of genetic markers. We observed strong population structure between Western and Eastern US populations, but no evidence of any population structure between different latitudes within the continental United States, suggesting that there are no broad-scale adaptations occurring in response to differences in winter climates. We detect admixture from Hawaii to the Western United States and from the Eastern United States to Europe, in agreement with previously identified introduction routes inferred from microsatellite analysis. We also detect potential signals of admixture from the Western United States back to Asia, which could have important implications for shipping and quarantine policies for exported agriculture. We anticipate this large genomic dataset will spur future research into the genomic adaptations underlying D. suzukii pest activity and development of novel control methods for this agricultural pest.

SBRT of ventricular tachycardia using 4pi optimized trajectories.

PURPOSE: To investigate the possible advantages of using 4pi-optimized arc trajectories in stereotactic body radiation therapy of ventricular tachycardia (VT-SBRT) to minimize exposure of healthy tissues. METHODS AND MATERIALS: Thorax computed tomography (CT) data for 15 patients were used for contouring organs at risk (OARs) and defining realistic planning target volumes (PTVs). A conventional trajectory plan, defined as two full coplanar arcs was compared to an optimized-trajectory plan provided by a 4pi algorithm that penalizes geometric overlap of PTV and OARs in the beam's-eye-view. A single fraction of 25 Gy was prescribed to the PTV in both plans and a comparison of dose sparing to OARs was performed based on comparisons of maximum, mean, and median dose. RESULTS: A significant average reduction in maximum dose was observed for esophagus (18%), spinal cord (26%), and trachea (22%) when using 4pi-optimized trajectories. Mean doses were also found to decrease for esophagus (19%), spinal cord (33%), skin (18%), liver (59%), lungs (19%), trachea (43%), aorta (11%), inferior vena cava (25%), superior vena cava (33%), and pulmonary trunk (26%). A median dose reduction was observed for esophagus (40%), spinal cord (48%), skin (36%), liver (72%), lungs (41%), stomach (45%), trachea (53%), aorta (45%), superior vena cava (38%), pulmonary veins (32%), and pulmonary trunk (39%). No significant difference was observed for maximum dose (p = 0.650) and homogeneity index (p = 0.156) for the PTV. Average values of conformity number were 0.86 ± 0.05 and 0.77 ± 0.09 for the conventional and 4pi optimized plans respectively. CONCLUSIONS: 4pi optimized trajectories provided significant reduction to mean and median doses to cardiac structures close to the target but did not decrease maximum dose. Significant improvement in maximum, mean and median doses for noncardiac OARs makes 4pi optimized trajectories a suitable delivery technique for treating VT.

Visual Acuity Outcomes after Phacoemulsification in Eyes with Good Visual Acuity before Cataract Surgery.

OBJECTIVE: to analyse cataract surgery outcomes and related factors in eyes presenting with good visual acuity. SUBJECT AND METHODS: A retrospective longitudinal study of patients undergoing phacoemulsification between 2014 and 2018 in Moorfields Eye Hospital was conducted. Pre- and post-operative visual acuities were analysed. Inclusion criteria were age ≥40 years and pinhole visual acuity ≥6/9 pre-operatively. Exclusion criteria were no post-operative visual acuity data. The visual acuity change variable was also defined according to post-operative visual acuity being above or below the Snellen 6/9 threshold. RESULTS: 2,720 eyes were included. The unaided logMAR visual acuity improved from 0.54 to 0.20 (p < 0.001), the logMAR visual acuity with glasses improved from 0.35 to 0.05 (p < 0.001), and the logMAR pinhole visual acuity improved from 0.17 to 0.13 (p < 0.001); 8.1% of patients had Snellen visual acuity <6/9 post-operatively. Mean follow-up period was 23.6 ± 9.9 days. In multivariate analysis, factors associated with visual acuity <6/9 post-operatively were age (OR = 0.96, 95% confidence interval [CI] [0.95, 0.98], p < 0.001), vitreous loss (OR = 0.21, 95% CI [0.08, 0.56], p = 0.002), and iris trauma (OR = 0.28, 95% CI [0.10, 0.82] p = 0.02). CONCLUSIONS: Visual acuity improved significantly, although at least 8.1% of them did not reach their pinhole preoperative visual acuity. Worse visual acuity outcomes were associated with increasing age, vitreous loss, and iris trauma. The 6/9 vision threshold may not be able to accurately differentiate those who may benefit from cataract surgery and those who may not.

Toward the combined optimization of dynamic axes (CODA) for stereotactic radiotherapy and radiosurgery using fixed couch trajectories.

PURPOSE: To develop a novel system for patient-specific combined optimization of couch, collimator, and gantry angles for use in volumetric modulated arc therapy (VMAT) treatment planning. The system was designed to produce highly compact dose distributions by extensively sampling the 4π space. Automated fixed couch trajectory planning was used to reduce normal tissue doses by avoiding beams-eye-view (BEV) overlap with organs-at-risk (OARs) and improve monitor unit (MU) efficiency through collimator angle optimization. METHODS: By merging distinct BEV objective functions used to optimize the couch rotation angle and collimator angle, a three-dimensional (3D) cost space (the CODA cube) was constructed with axes of gantry, couch, and collimator rotation angles. At each voxel in this CODA cube, the cost of implementing this combination of axes positions in fixed couch trajectories was quantified. The CODA cube was sampled and explored using a modified constrained Bellman-Ford algorithm to suggest low-cost fixed candidate arcs on each plane of the space, from which 10-arcs are chosen throughout the 3D space using a k-means clustering algorithm. These fixed couch trajectories were then imported into the Eclipse treatment planning system (v.11) and inverse-optimized according to clinical standards. Eight artificial cranial targets were contoured in a test-patient anatomy, and seven treatment plans were generated from combinations of three and four targets. The CODA cube optimized plans were compared to standard 4-arc VMAT plans for cranial stereotactic radiotherapy/surgery that were optimized for the same sets of targets; maximum dose to each OAR, V12Gy to normal brain, conformity, and total MUs were compared. Both planning methods were inverse-optimized with identical dosimetric objectives. RESULTS: CODA plans resulted in a reduction in maximum dose to OARs of 20.6% (P < 0.01), with maximum brainstem dose decreased by 2.63 Gy (P = 0.031) on average when compared to the standard arc arrangement. The mean reduction in total MU was 8.6% (P = 0.156), the mean increase in the inverse of the van't Riet conformation number was 0.1%, (P = 0.67) and the mean decrease in normal brain tissue receiving 12 Gy or higher was 3.9% (P = 0.16), when compared to the standard VMAT arc configuration (n = 7). CONCLUSIONS: The optimization of couch, collimator, and gantry angles simultaneously using a 3D optimization space achieved improvement on multiple clinical metrics when compared to the standard VMAT arc configuration. A statistically significant sparing to OAR maximum doses was seen. Combining these optimizations may yield superior results to independent optimization.

Systematic Review of Handoff Mnemonics Literature.

A systematic review of published English-language articles on handoffs is conducted (1987 to June 4, 2008). Forty-six articles describing 24 handoff mnemonics are identified by trained reviewers. The majority (82.6%) have been published in the last 3 years (2006-2008), and SBAR (Situation, Background, Assessment, Recommendation) is the most frequently cited mnemonic (69.6%). Of 7 handoff research articles, only 4 study mnemonics. All 4 of these studies have relatively small sample sizes (10-100) and lack validated instruments. Only 1 study has obtained IRB approval. Scientifically rigorous research studies are needed to assess the effectiveness of handoff mnemonics. These should be published in the peer-reviewed literature using the Standards for QUality Improvement Reporting Excellence (SQUIRE) guidelines.

Radical Chain Reduction of CCl4 Initiated by Illumination of SPEEK Solutions.

Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction formed chloride ions whose concentration increased linearly with time in solutions free of O2, whereas slower reductions occurred in the presence of air. Utilization of formate buffer as the H-atom donor yielded photoreactions at least 10 times faster than those in the presence of PVA and generated CHCl3 as another reaction product. The quantum yield of chloride ion formation, ø(Cl-), was found to be a function of both the SPEEK concentration and concentration of formate buffer. Whereas the quantum efficiency increased steadily with decreasing solution acidity, a drastic surge in the reaction rate occurred in neutral solutions. ø(Cl-) first increased rapidly to a maximum value exceeding 1 at pH 7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0 is the light intensity, and the occurrence of postirradiation formation of Cl- through the reduction of CCl4 in the dark are further evidence that the photoreaction proceeded by a chain process. Several of the kinetic features were rationalized by means of a mechanism involving the α-hydroxy radicals of SPEEK and •CCl3 as chain carriers.

Photogeneration of H2O2 in Water-Swollen SPEEK/PVA Polymer Films.

Efficient reduction of O2 took place via illumination with 350 nm photons of cross-linked films containing a blend of sulfonated poly(ether etherketone) and poly(vinyl alcohol) in contact with air-saturated aqueous solutions. Swelling of the solid macromolecular matrices in H2O enabled O2 diffusion into the films and also continuous extraction of the photogenerated H2O2, which was the basis for a method that allowed quantification of the product. Peroxide formed with similar efficiencies in films containing sulfonated polyketones prepared from different precursors and the initial photochemical process was found to be the rate-determining step. Generation of H2O2 was most proficient in the range of 4.9 ≤ pH ≤ 8 with a quantum yield of 0.2, which was 10 times higher than the efficiencies determined for solutions of the polymer blend. Increases in temperature as well as [O2] in solution were factors that enhanced the H2O2 generation. H2O2 quantum yields as high as 0.6 were achieved in H2O/CH3CN mixtures with low water concentrations, but peroxide no longer formed when film swelling was suppressed. A mechanism involving reduction of O2 by photogenerated α-hydroxy radicals from the polyketone in competition with second-order radical decay processes explains the kinetic features. Higher yields result from the films because cross-links present in them hinder diffusion of the radicals, limiting their decay and enhancing the oxygen reduction pathway.

Laparoscopic nephrectomy - Pfannenstiel or expanded port site specimen extraction: a systematic review and meta-analysis.

INTRODUCTION: To anaylse the current evidence regarding the safety, feasibility and advantages of intact specimen extraction via various extraction sites after conventional laparoscopic nephrectomy (LN). MATERIAL AND METHODS: A comprehensive literature search was performed identifying studies evaluating outcomes from Pfannenstiel (PFN) versus extended port site (EPS) extraction sites, after conventional laparoscopic nephrectomy/nephroureterectomy (LRN/LNU) and donor nephrectomy (LDN). Outcome measures included procedure duration, incision length, duration of inpatient stay, analgesic requirements, complications and warm ischemia time (for donor nephrectomy cases). RESULTS: This systematic review of five comparative studies found no significant difference in morbidity, wound length, wound complications or opioid consumption across all studies. Inpatient stay (p = 0.03) and estimated blood loss (p = 0.03) were significantly less in favour of a PFN extraction site. When comparing radical nephrectomy cases alone, the PFN group had a shorter procedure time (NS), less estimated blood loss (p = 0.04), shorter inpatient stay (p <0.05), significantly less morphine use (p <0.006) and fewer wound complications. CONCLUSIONS: This review demonstrates the viability of retrieving a nephrectomy specimen/graft through a PFN incision in relation to the benefits of cosmesis and reduced pain. As reported in several trials, morbidity is not significantly increased and key outcome measures, such as duration of inpatient stay, pain scores, complications, analgesic requirements and time taken to return to normal activities, remain non-inferior. This study is limited by the small number of generally low quality studies available for analysis. Further well-constructed randomised controlled trials are needed to shed more light on this subject area.

Translational research will fail without surgical leadership: SCOTRRCC a successful surgeon-led Nationwide translational research infrastructure in renal cancer.

BACKGROUND: High quality human biosamples with associated high quality clinical data are essential for successful translational research. Despite this, the traditional approach is for the surgeon to act as a technician in the tissue collection act. Biomarker research presents multiple challenges and the field is littered with failures. Tissue quality, poor clinical information, small sample numbers and lack of validation cohorts are just a few reasons for failure. It is clear that the surgeon involved in tissue acquisition must be fully engaged in the process of biosampling for a specific condition, as this will negate many of the issues for translational research failure due to an inadequate bioresource. APPROACH: In this Matter for Debate paper, the Scottish Collaboration On Translational Research into Renal Cell Cancer (SCOTRRCC) is discussed as an example of a urological surgery lead bioresource which has resulted in a National collection of renal cancer tissue and blood (from over 900 patients to date), negating all of the traditional issues with biobanks because of close enagagement and acknowledgement of urologists and uropathologists from seven centres around Scotland. SCOTRRCC has leveraged renal cancer research in Scotland resulting in several high impact publications and providing a springboard for future research in this disease in Scotland and beyond. CONCLUSIONS: The SCOTRRCC model presented here can be transferred to other surgical disciplines for success in translational research.

Resident and attending physician perception of maladaptive response to stress in residents.

BACKGROUND: Residency stress has been shown to interfere with resident well-being and patient safety. We developed a survey research study designed to explore factors that may affect perception of a maladaptive response to stress. METHODS: A 16-item survey with 12 Likert-type perception items was designed to determine how often respondents agreed or disagreed with statements regarding the resident on the trigger tape. A total of 438 respondents from multiple institutions completed surveys. RESULTS: Attending physicians were more likely than residents to agree that the resident on the trigger tape was impaired, p<0.0001; needed to seek professional counseling, p=0.0003; should be removed from the service, p=0.002; was not receiving adequate support from the attending physician, p=0.007; and was a risk to patient safety, p=0.02. Attending physicians were also less likely to agree that the resident was a good role model, p=0.001, and that the resident should be able to resolve these issues herself/himself, p<0.0001. CONCLUSION: Our data suggest that resident physicians may not be able to adequately detect maladaptive responses to stress and that attending physicians may be more adept at recognizing this problem. More innovative faculty and resident development workshops should be created to teach and encourage physicians to better observe and detect residents who are displaying maladaptive responses to stress.

Intraocular lens scaffold to facilitate intraocular lens exchange.

UNLABELLED: We describe a technique of intraocular lens (IOL) exchange in patients with post-refractive surgery IOL power error or patients who are dissatisfied with the optical performance of the IOL. The technique involves the presence of 2 IOLs in the eye: the offending IOL, which is manipulated out of the capsular bag into the anterior chamber, and the corrective IOL, which is inserted into the bag. The anteriorly elevated IOL is transected with the IOL cutting scissors, while the corrective IOL acts as a scaffold for the posterior capsule. The technique provides continuous distension of the bag with the IOL, which prevents damage to the posterior capsule and acts as a barrier to vitreous prolapse in cases of an open posterior capsule; it also prevents slippage of the optic during transection of the IOL being removed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.