ERAS for Ambulatory TURBT: Enhancing Bladder Cancer Care (EMBRACE) randomised controlled trial protocol.

INTRODUCTION: Transurethral resection of bladder tumour (TURBT) is one of the more common procedures performed by urologists. It is often described as an 'incision-free' and 'well-tolerated' operation. However, many patients experience distress and discomfort with the procedure. Substantial opportunity exists to improve the TURBT experience. An enhanced recovery after surgery (ERAS) protocol designed by patients with bladder cancer and their providers has been developed. METHODS AND ANALYSIS: This is a single-centre, randomised controlled trial to investigate the effectiveness of an ERAS protocol compared with usual care in patients with bladder cancer undergoing ambulatory TURBT. The ERAS protocol is composed of preoperative, intraoperative and postoperative components designed to optimise each phase of perioperative care. 100 patients with suspected or known bladder cancer aged ≥18 years undergoing initial or repeat ambulatory TURBT will be enrolled. The change in Quality of Recovery 15 score, a measure of the quality of recovery, between the day of surgery and postoperative day 1 will be compared between the ERAS and control groups. ETHICS AND DISSEMINATION: The trial has been approved by the Johns Hopkins Institutional Review Board #00392063. Participants will provide informed consent to participate before taking part in the study. Results will be reported in a separate publication. TRIAL REGISTRATION NUMBER: NCT05905276.

Natural autophagy activators: A promising strategy for combating photoaging.

BACKGROUND: Photodamage to the skin stands out as one of the most widespread epidermal challenges globally. Prolonged exposure to sunlight containing ultraviolet radiation (UVR) instigates stress, thereby compromising the skin's functionality and culminating in photoaging. Recent investigations have shed light on the importance of autophagy in shielding the skin from photodamage. Despite the acknowledgment of numerous phytochemicals possessing photoprotective attributes, their potential to induce autophagy remains relatively unexplored. PURPOSE: Diminished autophagy activity in photoaged skin underscores the potential benefits of restoring autophagy through natural compounds to enhance photoprotection. Consequently, this study aims to highlight the role of natural compounds in safeguarding against photodamage and to assess their potential to induce autophagy via an in-silico approach. METHODS: A thorough search of the literature was done using several databases, including PUBMED, Science Direct, and Google Scholar, to gather relevant studies. Several keywords such as Phytochemical, Photoprotection, mTOR, Ultraviolet Radiation, Reactive oxygen species, Photoaging, and Autophagy were utilized to ensure thorough exploration. To assess the autophagy potential of phytochemicals through virtual screening, computational methodologies such as molecular docking were employed, utilizing tools like AutoDock Vina. Receptor preparation for docking was facilitated using MGLTools. RESULTS: The initiation of structural and functional deterioration in the skin due to ultraviolet radiation (UVR) or sunlight-induced reactive oxygen species/reactive nitrogen species (ROS/RNS) involves the modulation of various pathways. Natural compounds like phenolics, flavonoids, flavones, and anthocyanins, among others, possess chromophores capable of absorbing light, thereby offering photoprotection by modulating these pathways. In our molecular docking study, these phytochemicals have shown binding affinity with mTOR, a negative regulator of autophagy, indicating their potential as autophagy modulators. CONCLUSION: This integrated review underscores the photoprotective characteristics of natural compounds, while the in-silico analysis reveals their potential to modulate autophagy, which could significantly contribute to their anti-photoaging properties. The findings of this study hold promise for the advancement of cosmeceuticals and therapeutics containing natural compounds aimed at addressing photoaging and various skin-related diseases. By leveraging their dual benefits of photoprotection and autophagy modulation, these natural compounds offer a multifaceted approach to combatting skin aging and related conditions.

Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration.

Purpose: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy. Design: Phase I, multicenter, prospective, open-label, dose-escalation trial. Participants: Patients with wAMD and evidence of prior anti-VEGF therapy response. Methods: Patients received a single intravitreal injection of EYP-1901. Main Outcome Measures: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates. Results: Seventeen patients enrolled in the 440 µg (3 patients), 1030 µg (1 patient), 2060 µg (8 patients), and 3090 µg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 µm and +2.4 µm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months. Conclusion: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Photoprotective efficacy of Sunset Yellow via inhibition of type-I and type-II pathway under exposure of sunlight.

Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various skin-related issues such as aging, allergies, and cancer. While several photo-protectants offer defense against ultraviolet radiation (UV-R), their effectiveness is often limited by photo-instability. Sunset Yellow (SY), an FDA-approved food dye, possesses significant UV-R and visible light absorption properties. However, its photoprotective potential has remained unexplored. Our investigation reveals that SY exhibits remarkable photostability for up to 8 h under both UV-R and sunlight. Notably, SY demonstrates the ability to quench ROS, including singlet oxygen (1O2), superoxide radicals ( O 2 · - $$ {\mathrm{O}}_2^{\cdotp -} $$ ), and hydroxyl radicals (·OH) induced by rose bengal, riboflavin and levofloxacin, respectively. Moreover, SY proves effective in protecting against the apoptotic and necrotic cell death induced by the phototoxicant chlorpromazine (CPZ) in HaCaT cells. Further, it was observed that SY imparts photoprotection by inhibiting intracellular ROS generation and calcium release. Genotoxicity evaluation provides additional evidence supporting SY's photoprotective effects against CPZ-induced DNA damage. In conclusion, these findings underscore the potential of SY as a promising photoprotective agent against the toxic hazards induced by phototoxicants, suggesting its prospective application in the formulation of broad-spectrum sunscreens.

Digital health literacy among the ageing population: A comparative cross-sectional study between rural and urban Telangana, India.

Background: Digital health literacy (DHL) is the confluence where health literacy meets digital literacy. DHL has been labelled as one of the digital determinants of health by the World Health Organization. The present study estimated and compared the DHL between Telangana's urban and rural ageing adults, and their potential determinants. Methods: A cross-sectional study was undertaken among 318 of the ageing individuals (≥45 years) of Hyderabad, visiting the primary health centres in the rural and urban field practice during March 2023. A Telugu version of the eHealth literacy scale (eHEALS) and health literacy scale tools were administered by the interviewers. Adjusted analysis was conducted by multiple linear regression method. Results: Overall, 20.4% of the study participants had good DHL, with a similar proportion between rural and urban areas (rural-20.1% and urban-20.8%, p value-0.889). The median eHealth literacy score among the study participants was 8. While 36.5% and 45.9% had smartphones and standard analogue phones, respectively in urban areas, only 19.5% and 38.4% had smartphones and standard analogue phones, respectively in rural areas. Computer usage in the past month, higher educational qualification, and ownership of mobile phones were significant determinants of DHL. A mild but significant correlation between DHL and health literacy screening scores was found. Conclusion: Considering the low DHL among the ageing population, enabling environment with enhanced access to mobile phones/smartphones and familiarity with information and communication technology gadgets must be established to improve their DHL.

An early case of successful peripheral nerve repair in 1880: Francis L. Parker, MD.

The modern technique of epineural suture repair, along with a detailed reporting of functional restoration, came from Carl Hueter in 1873. While there is extensive information on peripheral nerve surgery throughout recorded history leading up to the 1800s, little early American scientific literature is available. While Schwann, Nissl, and Waller were publishing their work on nerve anatomy and physiology, Francis LeJau Parker was born. The South Carolina native would go on to describe one of the first American cases of peripheral nerve repair with the restoration of function. Francis Parker was born in 1836 in Abbeville, South Carolina. He gained local notoriety as one of the first American surgeons to suture a severed nerve, resulting in restored function. The case dates back to 1880, when a patient presented to his clinic with severing of the posterior interosseous nerve. The details of this case come from the archives of the South Carolina Medical Association. The authors reviewed these records in detail and provide a case description of nerve repair not previously reported in the modern literature. The history, neurological examination, and details of the case provide insight into the adroit surgical skills of Dr. Parker.

PReoperative very low-Energy diets for obese PAtients undergoing non-bariatric surgery Randomized Evaluation (PREPARE): a protocol for a pilot randomized controlled trial.

BACKGROUND: Patients with obesity presenting in need of surgical intervention are at 2-to-sixfold higher risk of prolonged hospitalization, infectious morbidity, venous thromboembolism, and more. To mitigate some of these concerns, prescribed preoperative weight loss via very low-energy diets (VLEDs) has become a standard of care for patients with obesity undergoing bariatric surgery. While VLEDs have become standard prior to bariatric surgery, their application in other surgical settings remains limited. A large, definitive trial is required to resolve the uncertainty surrounding their use in these patients. Prior to a definitive trial to compare the efficacy of VLEDs in patients with obesity undergoing major non-bariatric surgery, we require a pilot trial. We argue a pilot trial will provide the following critical feasibility insights: (1) assessment of recruitment ability, (2) evaluation of adherence to VLED regimens, and (3) assessment of our ability follow patients completely. METHODS: The proposed trial will be a multi-center, surgeon, outcome assessor, and data-analyst blinded, parallel pilot randomized controlled trial (RCT). Patients older than 18 years of age with a body mass index (BMI) of greater than 30 kg/m2 undergoing major elective non-bariatric surgery will be eligible for inclusion. Consecutive patients will be allocated 1:1 according to a computer-generated randomization schedule. Randomization will be stratified by center and will employ randomly permutated blocks. All patients in the intervention group will receive standard patient counseling on weight loss and an active VLED protocol. The preoperative VLED protocol will utilize commercially available weight loss products for three weeks preoperatively. The primary outcomes (randomization percentage, recruitment rate, intervention adherence, follow-up completion, network development) will assess feasibility. Descriptive statistics will be used to characterize the study sample. DISCUSSION: The PREPARE pilot RCT will aim to provide feasibility and safety data that will allow for the successful completion of the definitive PREPARE trial that has the potential to provide practice changing data pertaining to the regular use of VLEDs as a means of pre-habilitation for patients with obesity undergoing major non-bariatric surgery. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (reference #NCT05918471) on June 23, 2023.

The impact of robotic rectal cancer surgery at a Canadian regional cancer centre: a retrospective cohort study.

BACKGROUND: Although robotic surgery has several advantages over other minimally invasive surgery (MIS) techniques for rectal cancer surgery, the uptake in Canada has been limited owing to a perceived increase in cost and lack of training. The objective of this study was to determine the impact of access to robotic surgery in a Canadian setting. METHODS: We conducted a retrospective cohort study involving consecutive adults undergoing surgical resection for rectal cancer between 2017 and 2020. The primary exposure was access to robotic surgery. Outcomes included MIS utilization, short-term outcomes, total cost of care, and quality of surgical resection. We completed univariate and multivariate analyses. RESULTS: We included 171 individuals in this cohort study (85 in the prerobotic period and 86 in the robotic period). The 2 groups had similar baseline characteristics. A higher proportion of individuals underwent successful MIS in the robotic phase (86% v. 46%, p < 0.001). Other benefits included a shorter mean length of hospital stay (5.1 d v. 9.2 d, p < 0.001). The quality of surgical resection was similar between groups. The total cost of care was $16 746 in the robotic period and $18 808 in the prerobotic period (mean difference -$1262, 95% confidence interval -$4308 to $1783; p = 0.4). CONCLUSION: Access to robotic rectal cancer surgery increased successful completion of MIS and shortened hospital stay, with a similar total cost of care. Robotic rectal cancer surgery can enhance patient outcomes in the Canadian setting.

Phenotypic Clusters and Multimorbidity in Hypermobile Ehlers-Danlos Syndrome.

Objective: To perform a retrospective clinical study in order to investigate phenotypic penetrance within a large registry of patients with hypermobile Ehlers-Danlos syndrome (hEDS) to enhance diagnostic and treatment guidelines by understanding associated comorbidities and improving accuracy in diagnosis. Patients and Methods: From May 1, 2021 to July 31, 2023, 2149 clinically diagnosed patients with hEDS completed a self-reported survey focusing on diagnostic and comorbid conditions prevalence. K-means clustering was applied to analyze survey responses, which were then compared across gender groups to identify variations and gain clinical insights. Results: Analysis of clinical manifestations in this cross-sectional cohort revealed insights into multimorbidity patterns across organ systems, identifying 3 distinct patient groups. Differences among these phenotypic clusters provided insights into diversity within the population with hEDS and indicated that Beighton scores are unreliable for multimorbidity phenotyping. Conclusion: Clinical data on the phenotypic presentation and prevalence of comorbidities in patients with hEDS have historically been limited. This study provides comprehensive data sets on phenotypic presentation and comorbidity prevalence in patients with hEDS, highlighting factors often overlooked in diagnosis. The identification of distinct patient groups emphasizes variations in hEDS manifestations beyond current guidelines and emphasizes the necessity of comprehensive multidisciplinary care for those with hEDS.

Salpingectomy for ovarian cancer prevention: Video education for the surgeon.

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on the knowledge mobilization of a standard surgical approach for surgeons (Hanley et al., 2017, Morelli et al., 2013). Resources for accomplishing this knowledge mobilization activity are needed. We therefore aim to create a peer-reviewed, publicly available surgical instructional video that facilitates standardization of the practice of salpingectomy for the purpose of OC prevention. Content creation was generated by a team of surgeon stakeholders, medical illustrators, instructional designers, and health education specialists. Expert gynecologic surgeons were filmed performing salpingectomy in order to build a video library. Accurate illustration and editing of live video footage was executed to support surgeons in visualizing key anatomic landmarks to ensure safe and complete fallopian tube excision. Review of eligibility criteria, fundamentals of preoperative counseling, and strategic and technical points were prioritized. This endeavor is strictly educational, with no commercial benefit. Publicly available, peer-reviewed surgical education tools will help us collaborate to safely and equitably expand OS within and beyond the current scope of surgical practice.

A systematic review and meta-analysis of oncological outcomes with transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer. METHOD: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021. RESULTS: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I2 = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I2 = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant. CONCLUSION: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected.

A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

Emergency Colorectal Surgery in Those with Cirrhosis: A Population-based Study Assessing Practice Patterns, Outcomes and Predictors of Mortality.

Background: Those with cirrhosis who require emergency colorectal surgery are at risk for poor outcomes. Although risk predictions models exists, these tools are not specific to colorectal surgery, nor were they developed in a contemporary setting. Thus, the objective of this study was to assess the outcomes in this population and determine whether cirrhosis etiology and/or the Model for End Stage Liver Disease (MELD-Na) is associated with mortality. Methods: This population-based study included those with cirrhosis undergoing emergent colorectal surgery between 2009 and 2017. All eligible individuals in Ontario were identified using administrative databases. The primary outcome was 90-day mortality. Results: Nine hundred and twenty-seven individuals (57%) (male) were included. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (50%) and alcohol related (32%). Overall 90-day mortality was 32%. Multivariable survival analysis demonstrated those with alcohol-related disease were at increased risk of 90-day mortality (hazards ratio [HR] 1.53, 95% confidence interval [CI] 1.2-2.0 vs. NAFLD [ref]). Surgery for colorectal cancer was associated with better survival (HR 0.27, 95%CI 0.16-0.47). In the subgroup analysis of those with an available MELD-Na score (n = 348/927, 38%), there was a strong association between increasing MELD-Na and mortality (score 20+ HR 6.6, 95%CI 3.9-10.9; score 10-19 HR 1.8, 95%CI 1.1-3.0; score <10 [ref]). Conclusion: Individuals with cirrhosis who require emergent colorectal surgery have a high risk of postoperative complications, including mortality. Increasing MELD-Na score is associated with mortality and can be used to risk stratify individuals.

Smartphone Application Versus Standard Instruction for Colonoscopic Preparation: A Randomized Controlled Trial.

OBJECTIVE: To compare smartphone application (Colonoscopic Preparation) instructions versus paper instructions for bowel preparation for colonoscopy. BACKGROUND: Adhering to bowel preparation instructions is important to ensure a high-quality colonoscopy. PATIENTS AND METHODS: This randomized controlled trial included individuals undergoing colonoscopy at a tertiary care hospital. Individuals were randomized (1:1) to receive instructions through a smartphone application or traditional paper instructions. The primary outcome was the quality of the bowel preparation as measured by the Boston Bowel Preparation Score. Secondary outcomes included cecal intubation and polyp detection. Patient satisfaction was assessed using a previously developed questionnaire. RESULTS: A total of 238 individuals were randomized (n = 119 in each group), with 202 available for the intention-to-treat analysis (N = 97 in the app group and 105 in the paper group). The groups had similar demographics, indications for colonoscopy, and type of bowel preparation. The primary outcome (Boston Bowel Preparation Score) demonstrated no difference between groups (Colonoscopic Preparation app mean: 7.26 vs paper mean: 7.28, P = 0.91). There was no difference in cecal intubation (P = 0.37), at least one polyp detected (P = 0.43), or the mean number of polyps removed (P = 0.11). A higher proportion strongly agreed or agreed that they would use the smartphone app compared with paper instructions (89.4% vs 70.1%, P = 0.001). CONCLUSIONS: Smartphone instructions performed similarly to traditional paper instructions for those willing to use the application. Local patient preferences need to be considered before making changes in the method of delivery of medical instructions.

Applying the fragility index to randomized controlled trials evaluating total neoadjuvant therapy for rectal cancer: A methodological survey.

BACKGROUND: Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). We designed the present study to assess the robustness of the randomized controlled trials (RCTs) evaluating contemporary TNTs for LARC using the fragility index (FI). MATERIALS AND METHODS: Relevant articles were identified through a review article by Johnson et al. in the Canadian Journal of Surgery. Dichotomous outcomes within these RCTs were eligible for inclusion if the reported effect size had a p-value < 0.05. The main outcome was FI for each included outcome. Walsh et al.'s method of calculating FI was utilized. Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Risk of bias was assessed using Cochrane recommended tools. RESULTS: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups. Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. Approximately half (n = 13) were oncologic outcomes. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0 %) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho = -0.5594) and greater loss to follow-up (rho = -0.4394), while higher FI was associated with large study size (rho = 0.5120). CONCLUSIONS: The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most outcomes were fragile, as determined by the FI. This survey is limited by the number of included studies.

Venous invasion detectable only by elastic stain shows weak prognostic value in colon cancer.

AIMS: Large venous invasion (VI) is prognostically significant in colon cancer. The increased use of elastic stains by pathologists results in higher VI detection rates compared to routine stains alone. This study assesses the prognostic value of VI detected by elastic versus routine stains. METHODS AND RESULTS: Colon cancers resected between 2014 and 2017 underwent pathology slide review for VI. Cases without VI on routine stain were stained by elastic trichrome and re-examined. Demographic, clinical, pathological and outcome data were gathered by retrospective review. Kaplan-Meier curves with log-rank tests were performed for survival categorised by VI status. Cox regression was performed for multivariate analysis. Of 277 cases, 97 (35%) showed VI by routine stain alone, with an additional 58 (21%) discovered by subsequent elastic stains. Thus, elastic trichrome increased VI detection by 60%. However, only VI detected by routine stain showed worse overall survival (P < 0.001). VI detected by elastic stain only was not prognostically different from cases without VI (P = 0.428). For stage 2 cancers, VI was not prognostically significant regardless of method of detection. For stage 3 cases, only VI detected by routine stain was prognostic for overall survival (P = 0.002) with a hazard ratio of 4.04 by multivariate regression (P = 0.028). CONCLUSIONS: VI detectable only by elastic stains do not show prognostic significance for survival in colon cancer. For pathologists with high baseline VI detections rates on routine stain, reflexive use of elastic stain may be of limited value.

Urologist-level variation in the management of T1a renal cell carcinoma: A population-based cohort study.

OBJECTIVES: Lack of strict indications in current guidelines have led to significant variation in management patterns of small renal masses. The impact of the urologist on the management approach for patients with small renal masses has not been explored previously. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, patients aged ≥66 years diagnosed with small renal masses from January 1, 2004 to December 31, 2013 were identified and assigned to primary urologists. Mixed-effects logistic models were used to evaluate factors associated with different management approaches, estimate urologist-level probabilities of each approach, assess management variation, and determine urologist impact on choice of approach. RESULTS: A total of 12,402 patients with 2,794 corresponding primary urologists were included in the study. At the individual urologist level, the estimated case-adjusted probability of different approaches varied markedly: nonsurgical management (mean, 12.8%; range, 4.9%-36.1%); thermal ablation (mean, 10.8%; range, 2.4%-66.3%); partial nephrectomy (mean, 30.1%; range, 10.1%-66.6%); and radical nephrectomy (mean, 40.4%; range, 17.7%-71.6%). Compared to patient and tumor characteristics, the primary urologist was a more influential measured factor, accounting for 13.6% (vs. 12.9%), 33.8% (vs. 2.1%), 15.1% (vs. 8.4%), and 13.5% (vs. 4.0%) of the variation in management choice for nonsurgical management, thermal ablation, partial nephrectomy, and radical nephrectomy, respectively. CONCLUSIONS: Significant variation exists in the management of small renal masses and appears to be driven primarily by urologist preference and practice patterns. Our findings emphasize the need for unified guidance regarding management of these masses to reduce unwarranted variation in care.

Delayed Versus Early Laparoscopic Appendectomy for Adult Patients With Acute Appendicitis: A Randomized Controlled Trial.

OBJECTIVE: To assess whether delaying appendectomy until the following morning is non-inferior to immediate surgery in those with acute appendicitis presenting at night. BACKGROUND: Despite a lack of supporting evidence, those with acute appendicitis who present at night frequently have surgery delayed until the after morning. METHODS: The delay trial is a noninferiority randomized controlled trial conducted between 2018 and 22 at 2 tertiary care hospitals in Canada. Adults with imaging confirmed acute appendicitis who presented at night (8:00 pm -4:00 am ). Delaying surgery until after 6:00 am was compared with immediate surgery. The primary outcome was 30-day postoperative complications. An a prior noninferiority margin of 15% was deemed clinically relevant. RESULTS: One hundred twenty-seven of the planned 140 patients were enrolled in the Delayed Versus Early Laparoscopic Appendectomy (DELAY) trial (59 in the delayed group and 68 in the immediate group). The two groups were similar at baseline. The mean time between the decision to operate and surgery was longer in the delayed group (11.0 vs 4.4 hours, P < 0.0001). The primary outcome occurred in 6/59 (10.2%) of those in the delayed group versus 15/67 (22.4%) of those in the immediate group ( P = 0.07). The difference between groups met the a priori noninferiority criteria of +15% (risk difference -12.2%, 95% CI: -24.4% to +0.4%, test of noninferiority P < 0.0001). CONCLUSIONS: The DELAY study is the first trial to assess delaying appendectomy in those with acute appendicitis. We demonstrate the noninferiority of delaying surgery until the after morning.