Diversity and Inclusion on General Surgery, Integrated Thoracic Surgery, and Integrated Vascular Surgery Residency Program Websites.

BACKGROUND: Increasing diversity in medicine is receiving more attention, yet underrepresented in medicine (UiM) surgeons remain a small fraction of all surgeons. Whether surgical training programs attempt to attract UiM applicants to their programs, and therefore their specialties, through program website information is unclear. OBJECTIVE: To analyze the scope of diversity and inclusion (D&I) related information on US allopathic and osteopathic general surgery, integrated thoracic surgery, and integrated vascular surgery residency program websites. METHODS: Residency programs were identified through the Electronic Residency Application Service (ERAS) in July 2020. We searched surgical program websites and collected data on the presence or absence of variables labeled "diversity & inclusion" or "underrepresented in medicine." Variables found on program websites as well as sites linked to the program website were included. We excluded programs identified in ERAS as fellowship training programs. Programs without webpages were also excluded. RESULTS: We identified 425 residency programs and excluded 22 from data analysis. Only 75 of the 403 included programs (18.6%) contained D&I-related information. The presence of individual variables was also low, ranging from 4.5% for opportunities related to early exposure to the specialty to 11.1% for a written or video statement of commitment to D&I. CONCLUSIONS: In 2020, as recruitment and interviews moved entirely online, few US allopathic and osteopathic general surgery, integrated thoracic surgery, and integrated vascular surgery residency programs provided D&I-related information for residency applicants on their program websites.

Takotsubo stress-induced cardiomyopathy following robotic radical cystectomy.

Cardiac complications following surgery can be devastating especially if it is unrecognized. We present a case of a stress-induced cardiomyopathy that occurred in postoperative period following a robotic radical cystectomy and urinary diversion. While most cases of stress-induced cardiomyopathy, also known as Takotsubo cardiomyopathy, are transient and with little to no long term clinical effects, a small number of patients can develop severe complications. This has not been reported in urologic literature and the unique characteristics of this cardiac condition are reviewed.

Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans.

Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, hyposmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. Here, we present investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. Our findings demonstrate that nematode survival of a hyposmotic environment during anoxia (hyposmotic anoxia) depends on the nematode's ability to engage in glycogen metabolism. We also present results of a genome-wide screen for genes affecting glycogen content and localization in the nematode, showing that nematode survival of hyposmotic anoxia depends on a large number of these genes. Finally, we show that an inability to engage in glycogen synthesis results in suppression of the enhanced survival phenotype observed in daf-2 insulin-like pathway mutants, suggesting that alterations in glycogen metabolism may serve as a basis for these mutants' resistance to hyposmotic anoxia.

Circulating Tumor Cells in Biochemical Recurrence of Prostate Cancer.

OBJECTIVE: Circulating tumor cells (CTCs) have known prognostic implications in metastatic castration-resistant prostate cancer, but little is known regarding its utility in biochemical recurrence (BR) of prostate cancer. The primary objectives were to determine whether CTCs are measurable in patients with BR and whether it can reliably predict prostate-specific antigen (PSA) increase and PSA doubling times (PSADTs). METHODS: BR was identified in patients after prostatectomy or radiation or both, with a PSA increase of ≥ 0.2 for prior prostatectomy or > 2 mg/dL increase for post-nadir in prior radiotherapy. CTCs were enumerated at baseline at the time of study entry using the CellSearch (Janssen Diagnostics, Raritan, NJ) test. RESULTS: The median age for all 36 patients accrued was 69.5 years (range, 51-91) with a median PSA of 1.65 ng/mL (range, 0.2-65.8). Gleason scores ranged from 5 to 9 (median, 7). The majority had prostatectomy (n = 25), external beam radiotherapy (n = 9), CyberKnife (Accuray, Sunnyvale, CA) (n = 1), and combined radiohormonal therapy (n = 1). PSADT ranged from 0.35 to 55 months, with a median of 7.43 months. The incidence of positive CTCs was 8.3% (3 patients), of whom 2 had biopsy-proven bony lesions on presenting with equivocal scans and PSADTs of 2.27 and 3.08 months, respectively. The third CTC-positive patient had a PSADT of 4.99 months. CONCLUSIONS: Obtaining CTCs in unselected patients presenting with BR has a relatively low yield. However, obtaining a positive CTC raises the suspicion of the presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR.

Androgen receptor-target genes in african american prostate cancer disparities.

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging ("transcriptional convergence") on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs.

Surgical complications after robot-assisted laparoscopic radical prostatectomy: the initial 1000 cases stratified by the clavien classification system.

BACKGROUND AND PURPOSE: Complications after robot-assisted prostatectomy are widely reported and varied. Our goal was to determine the incidence of surgical complications resulting from robot-assisted laparoscopic radical prostatectomy (RALP) during the initial phase of a new robotics program that was developed by two surgeons without laparoscopic or robotic fellowship training. A secondary goal was to see if experience changed the incidence of complications with this technology. PATIENTS AND METHODS: A prospectively maintained database was used to evaluate the first 1000 consecutive patients who were treated with RALP from January 2004 to June 2009. The database was reviewed for evidence of complications in the perioperative period. All patients underwent robot-assisted laparoscopic radical prostatectomy by two surgeons. Complications were confirmed and supplemented by retrospectively reviewing the departmental morbidity and mortality reports, as well as the hospital records. The Clavien classification system, a standardized and validated scale for complication reporting, was applied to all events. The complication rate was determined per 100 patients treated and tested with logistic regression for a relationship with surgeon experience. RESULTS: Ninety-seven (9.7%) patients experienced a total of 116 complications; 81 patients experienced a single complication and 16 patients experienced ≥2 complications. The majority of complications (71%) were either grade I or II. The complication rate decreased with experience when the first 500 cases were compared with the latter 500 cases (P=0.007). All the data were reviewed retrospectively. Involvement of residents/fellows increased as primary surgeon experience improved. CONCLUSIONS: Complications after RALP are most commonly minor, requiring expectant or medical management only, even during the initiation of a RALP program. The complication rate improved significantly during the study period.

Rectal injury during robot-assisted radical prostatectomy: incidence and management.

PURPOSE: Rectal injury during robot-assisted radical prostatectomy is a rare but significant complication. Since the Clavien grading classification of complications does not include intraoperative injury without further sequelae, rectal injury may be underreported in the literature. We present what is to our knowledge the largest retrospective review to date of rectal injury and subsequent management. MATERIALS AND METHODS: We reviewed the records of 6,650 patients who underwent robot-assisted radical prostatectomy at a total of 6 institutions. Patient characteristics, perioperative parameters, pathological findings and rectal injury management were tabulated and analyzed for intraoperative predictors of outcome and subsequent management. RESULTS: A total of 11 rectal injury cases were identified of the 6,650 robot-assisted radical prostatectomies for a combined 0.17% incidence of rectal injury. Of rectal injuries 72.7% were identified intraoperatively and most did well with primary closure. Delayed recognition injury presented as rectourethral fistula without septic complications and required delayed fistula repair after primary diversion. We found no conclusive association of rectal injury with any patient parameter, intraoperative differences, pathological finding or surgeon experience. Posterior prostate plane dissection, including seminal vesicle dissection, is the crucial stage when rectal injury can occur and be identified. CONCLUSIONS: Our review of the records at 6 centers revealed a combined 0.17% incidence of rectal injury. This compares favorably to the incidence in modern open and laparoscopic radical prostatectomy series. No preoperative, intraoperative or pathological differences correlated with injury. Cases in which rectal injury was identified intraoperatively required fewer surgical repeat interventions but ultimately each group had acceptable long-term urinary and bowel function results.

Posterior rhabdosphincter reconstruction during robotic assisted radical prostatectomy: results from a phase II randomized clinical trial.

PURPOSE: Posterior rhabdosphincter reconstruction following radical prostatectomy was designed to improve early urinary continence. We executed a randomized clinical trial to test this conjecture in men undergoing robotic radical prostatectomy. MATERIALS AND METHODS: We conducted a phase II randomized clinical trial intended to detect a 25% difference in 3-month continence outcomes defined by a patient response of 0 or 1 to question 5 of the Expanded Prostate Cancer Index Composite questionnaire urinary domain, comparing standard running vesicourethral anastomosis (controls) to posterior rhabdosphincter reconstruction followed by standard running vesicourethral anastomosis (posterior rhabdosphincter reconstruction treated). Patients had clinically localized prostate cancer and were blinded. Surgeons were notified of computer randomization after prostate excision. Further continence outcomes were assessed by analysis of Expanded Prostate Cancer Index Composite questionnaire questions 1 and 12, International Prostate Symptom Score and 24-hour pad weights. Statistical significance was defined as p <0.05 RESULTS: A total of 94 patients were randomized, 47 to each arm. Preoperative clinical and functional variables were equivalent between study arms. There were no complications associated with either anastomotic technique. Of the 87 evaluable patients 62 (71.3%) met our 3-month continence definition. The null hypothesis was not rejected as 33 (81%) controls and 29 (63%) posterior rhabdosphincter reconstruction treated patients were continent at 3 months (chi-square p = 0.07, Fisher exact p = 0.1). Likewise there was no significant difference between arms in 24-hour pad weights (p = 0.14), International Prostate Symptom Score (p = 0.4), absence of daily leaks (p = 0.4) or perception of urinary function (p = 0.4). CONCLUSIONS: In this randomized clinical trial posterior rhabdosphincter reconstruction offered no advantage for return of early continence after robotic assisted radical prostatectomy.

Adaptive sugar provisioning controls survival of C. elegans embryos in adverse environments.

The ability to adapt to changing environmental conditions is essential to the fitness of organisms. In some cases, adaptation of the parent alters the offspring's phenotype [1-10]. Such parental effects are adaptive for the offspring if the future environment is similar to the current one but can be maladaptive otherwise [11]. One mechanism by which adaptation occurs is altered provisioning of embryos by the parent [12-16]. Here we show that exposing adult Caenorhabditis elegans to hyperosmotic conditions protects their offspring from these conditions but causes sensitivity to anoxia exposure. We show that this alteration of survival is correlated with changes in the sugar content of adults and embryos. In addition, mutations in gene products that alter sugar homeostasis also alter the ability of embryos to survive in hyperosmotic and anoxic conditions and engage in the adaptive parental effect. Our results indicate that there is a physiological trade-off between the presence of glycerol, which protects animals from hyperosmotic conditions, and glycogen, which is consumed during anoxia. These two metabolites play an essential role in the survival of worms in these adverse environments, and the adaptive parental effect we describe is mediated by the provisioning of these metabolites to the embryo.

Bladder neck contractures related to the use of Hem-o-lok clips in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: Recently, several large series of robot-assisted laparoscopic radical prostatectomy (RALP) have described a low incidence of bladder neck contractures (BNC). We have had a similar experience at our institution. Our objective is to describe our experience with BNC after RALP and a novel relationship to the use of Hem-o-lok Clips (HOLC). METHODS: We reviewed a database of patients who underwent RALP at our institution from January 2004 to September 2007 and identified patients with BNC or complications related to the use of HOLC. We performed a retrospective chart review to attempt to determine the cause of each BNC. We also performed a PubMed search and review of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. RESULTS: Of 524 patients undergoing RALP, 4 had a BNC develop, 2 of the BNCs were associated with HOLC migration and erosion into the vesicourethral anastomosis, and 1 was found to have HOLC migration within the bladder. A fifth patient had an anastomotic leak develop secondary to a HOLC that migrated into the bladder neck. Two similar cases of HOLC-related migration have been reported to MAUDE. CONCLUSIONS: When early BNC or unexplained urinary retention occurs after RALP, one should have a high index of suspicion for migration of HOLC. Clip use should be minimized on tissue immediately adjacent to the anastomosis, and every effort should be made to retrieve loose clips after the procedure.

Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study.

N-acetyltransferase-1 (NAT1) and N-acetyltransferase-2 (NAT2) are important in the metabolism of aromatic and heterocyclic amine carcinogens that induce prostate tumors in the rat. We investigated the association of genetic polymorphisms in NAT1 and NAT2, alone and in combination, with human prostate cancer. Incident prostate cancer cases and controls in a hospital-based case-control study were frequency-matched for age, race, and referral pattern. The frequency of slow acetylator NAT1 genotypes (NAT1*14, *15, *17) was 5.8% in controls but absent in cases. In contrast, in comparison with all other NAT1 genotypes the putative rapid acetylator NAT1 genotype (NAT1*10) was significantly higher in prostate cancer cases than controls (OR, 2.17; 95% CI, 1.08-4.33; P = 0.03). Combinations of NAT1*10 with NAT2 slow acetylator genotypes (OR, 5.08; 95% CI, 1.56-16.5; P = 0.008) or with NAT2 very slow (homozygous NAT2*5) acetylator genotypes (OR, 7.50; 95% CI, 1.55-15.4; P = 0.016) further increased prostate cancer risk. The results of this small pilot study suggest increased susceptibility to prostate cancer for subjects with combinations of NAT1*10 and slow (particularly very slow) NAT2 acetylator genotypes. This finding should be investigated further in larger cohorts and in other ethnic populations.