A Novel Cooling Device for Kidney Transplant Surgery.

Background: Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and graft survival. Circumventing WIT lies in maintaining renal hypothermia and efficiently performing the vascular anastomosis during this portion of the procedure. Although numerous methods of intra-operative renal cooling have been proposed, most suffer from practical limitations, and none have been widely adopted. Herein we describe a novel device specifically designed to maintain renal hypothermia during kidney transplant surgery.Methods: Aluminum tubing was organized in a serpentine pattern to create a malleable, form-fitting cooling jacket to manipulate renal allografts during transplant surgery. Adult porcine kidneys were used to test the device with 4°C saline as coolant. Kidneys were placed at 24°C; surface and core temperatures were monitored using implanted thermocouples. Anastomosis of porcine kidney vessels to GORE-TEX® vascular grafts in an ex-vivo operative field was performed to assess the functionality of the device.Results: The device maintained surface and core graft temperatures of ≤5°C after 60 minutes of WIT. Furthermore, the device provided hands-free retraction and support for the allograft. We found that ex-vivo anastomosis testing was enhanced by the presence of the cooling jacket.Conclusions: This proof-of-concept study demonstrated that our novel device is a practical tool for renal transplantation and can maintain sufficiently cool graft temperatures to mitigate WIT in an ex-vivo setting. This device is the first of its kind and has the potential to improve kidney transplant outcomes by eliminating WIT during graft implantation.

The Impact of Combined Warm and Cold Ischemia Time on Post-transplant Outcomes.

Background: Prolonged warm ischemia time (WIT) and cold ischemia time (CIT) are independently associated with post-transplant graft failure; their combined impact has not been previously studied. We explored the effect of combined WIT/CIT on all-cause graft failure following kidney transplantation. Methods: The Scientific Registry of Transplant Recipients was used to identify kidney transplant recipients from January 2000 to March 2015 (after which WIT was no longer separately reported), and patients were followed until September 2017. A combined WIT/CIT variable (excluding extreme values) was separately derived for live and deceased donor recipients using cubic splines; for live donor recipients, the reference group was WIT 10 to <23 minutes and CIT >0 to <0.42 hours, and for deceased donor recipients the WIT was 10 to <25 minutes and CIT 1 to <7.75 hours. The adjusted association between combined WIT/CIT and all-cause graft failure (including death) was analyzed using Cox regression. Secondary outcomes included delayed graft function (DGF). Results: A total of 137 125 recipients were included. For live donor recipients, patients with prolonged WIT/CIT (60 to ≤120 minutes/3.04 to ≤24 hours) had the highest adjusted hazard ratio (HR) for graft failure (HR = 1.61, 95% confidence interval [CI] = 1.14-2.29 relative to the reference group). For deceased donor recipients, a WIT/CIT of 63 to ≤120 minutes/28 to ≤48 hours was associated with an adjusted HR of 1.35 (95% CI = 1.16-1.58). Prolonged WIT/CIT was also associated with DGF for both groups although the impact was more driven by CIT. Conclusions: Combined WIT/CIT is associated with graft loss following transplantation. Acknowledging that these are separate variables with different determinants, we emphasize the importance of capturing WIT and CIT independently. Furthermore, efforts to reduce WIT and CIT should be prioritized.

Contexte: La période prolongée d'ischémie à chaud (WIT­warm ischemia time) et la période prolongée d'ischémie à froid (CIT­cold ischemia time) ont été associées de façon indépendante à une défaillance du greffon post-transplantation, mais leur effet combiné n'a jamais été étudié. Nous avons examiné l'effet combiné WIT/CIT sur la défaillance du greffon toutes causes confondues après une transplantation rénale. Méthodologie: Le Scientific Registry of Transplant Recipients a été utilisé pour identifier les receveurs d'une greffe de rein entre janvier 2000 et mars 2015 (date après laquelle la WIT n'a plus été rapportée séparément). Les patients ont été suivis jusqu'en septembre 2017. Une variable combinée WIT/CIT (excluant les valeurs extrêmes) a été dérivée de façon isolée pour les donneurs vivants et les donneurs décédés à l'aide d'une fonction spline cubique. La WIT du groupe référence pour les donneurs vivants se situait entre 10 et <23 minutes, et la CIT entre 0 et <0,42 heure; pour les donneurs décédés, la WIT se situait entre 10 et <25 minutes, et la CIT entre 1 et <7,75 heures. L'association corrigée entre une combinaison WIT/CIT et la défaillance du greffon toutes causes confondues (y compris le décès) a été analysée à l'aide de la régression de Cox. Les résultats secondaires incluaient une reprise retardée de la fonction du greffon (RRFG). Résultats: Un total de 137 125 receveurs d'un rein a été inclus. Dans le groupe des receveurs d'un organe provenant d'un donneur vivant, les patients avec une WIT/CIT prolongée (60 à ≤120 minutes/3,04 à ≤24 heures) présentaient un risque relatif corrigé plus élevé de défaillance du greffon (RRc: 1,61; IC 95 %: 1,14-2,29) par rapport au groupe de référence. Dans le groupe des receveurs d'un organe provenant d'un donneur décédé, une combinaison WIT/CIT de 63 à ≤120 minutes/28 à ≤48 heures a été associée à un RRc de 1,35 (IC 95 %: 1,16-1,58). La WIT/CIT prolongée a également été associée à une RRFG pour les deux groupes, bien que cet effet ait été davantage influencé par la CIT. Conclusion: La combinaison WIT/CIT est associée à la perte du greffon après la transplantation. Sachant qu'il s'agit de variables distinctes avec des déterminants différents, nous soulignons l'importance de rapporter la WIT et la CIT de façon indépendante. Qui plus est, les efforts visant à réduire la WIT et la CIT devraient être prioritaires.

Laparoscopic pyeloplasty practice patterns in Canada.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is a condition characterized by partial or complete obstruction of urine transport from the renal pelvis to the ureter and can present with intermittent flank pain, recurrent urinary tract infections, renal stones, or renal dysfunction. While historically, open pyeloplasty was the gold standard for surgical management, laparoscopic methods to repair UPJO have largely taken over as the preferred approach for adolescent and adult patients. Despite near universal adoption of laparoscopic pyeloplasty among Canadian urologists, it remains a technically complex procedure and considerable variability exists in the procedural steps performed. METHODS: An online survey was distributed to all urologists registered with the Canadian Urology Association (CUA). Participants were asked to describe their training background, comfort level with laparoscopic pyeloplasty, positioning preferences, procedural steps, and stenting practices. RESULTS: A total of 100 board-certified urologists completed our survey, with approximately half from a community setting and half with academic affiliations (56% and 43%, respectively). The vast majority (98%) reported preferring the Anderson-Hynes (dismembered) pyeloplasty technique. Other technical steps of the procedure were variable among respondents, with no discernable pattern. Those who felt most comfortable with the procedure tended to perform a larger volume of laparoscopic pyeloplasties annually or work at higher-volume institutions. CONCLUSIONS: Laparoscopic pyeloplasty remains a technically challenging procedure that many Canadian urologists are uncomfortable performing. With this publication, we hope to create discussion among urologists and to reveal procedural tips that may improve comfort in tackling these complex cases.

CanMEDS scholars: A national survey on urology residents' attitudes towards research during training.

INTRODUCTION: Participation in scholarly activity is an important tenet of residency training and is firmly entrenched in Canada since the introduction of CanMEDS roles by the Royal College of Physicians and Surgeons. As Canadian residency programs transition to competency-based training, it will remain important to understand how to best implement and encourage scholarly pursuits among resident trainees. The objective of this study was to understand the experiences, attitudes, and barriers that surgical residents face when pursuing research during their training. METHODS: An anonymous, cross-sectional, self-report questionnaire was administered to chief residents of all English-speaking urology programs in Canada in 2015. Questions were open- and close-ended, including an agreement score based on a five-point Likert scale. Questions addressed residents' involvement in and attitudes towards research, as well as their perceptions of the utility of research involvement during training. The residents were also asked about the support they received and potential areas to improve the attainment of this competency. Descriptive and correlative statistics were used to analyze the responses. RESULTS: There was a 100% overall response rate to the questionnaire. This study revealed that Canadian urology residents have a high rate of participation in scholarly work, with the vast majority (94%) publishing at least one manuscript with a mean of four papers. Despite this, there appeared to be significant variation in the respondent's experiences, including protected time for research. Furthermore, many residents appeared unconvinced of the importance of research involvement, with only 51% agreement that participation was important to their overall training. As well, a significant number of residents reported largely external, rather than internal, motivations for research participation, such as attaining a preferred fellowship (66% agreement). While the majority of respondents felt (66% agreement) that the scholar role was important in residency training, it would appear that significant barriers, including time and mentorship, limited the effectiveness of research participation to gain those competencies. CONCLUSIONS: The results of this self-report survey outline the significant differences in attitudes and experience towards mandatory research as a component of scholarship in Canadian urology training programs. As postgraduate medical education evolves, particularly with the uptake of competency-based medical education, programs and residents will need to address the motives and barriers to better foster academic pursuits during urology training.

Randomized, controlled trial of laser vs. bipolar plasma vaporization treatment of benign prostatic hyperplasia.

INTRODUCTION: Prostate vaporization technology is becoming a standard of care for treatment of moderate, symptomatic benign prostatic hyperplasia (BPH). We compared two transurethral prostate vaporization technologies with respect to cost, efficiency, efficacy, safety, and surgical team satisfaction. METHODS: Fifty-five patients meeting standardized symptom criteria for BPH were randomized to either Olympus Plasma ButtonTM or Biolitec EVOLVE® diode laser vaporization. Primary outcome of cost with secondary outcomes of clinical efficacy, resection time, surgical team satisfaction, and safety were analyzed. Followup was carried out at six and 12 weeks. Patient factors included baseline, as well as six- and 12-week International Prostate Symptom Score (IPSS) with quality of life (QoL) scores. We recorded surgical team satisfaction with a Likert-style survey investigating ease of set-up, reliability, efficiency, and ability to reach desired endpoint. All complications or side effects detected within three months and the resulting management were included in the cost analysis. RESULTS: Mean cost per patient was $3418 for the Olympus group and $4564 for Biolitec (p<0.05). Surgical vaporization time was significantly less for the Olympus group, 24.3 vs. 33.5 minutes (p<0.05). Surgical and nursing staff preferred the Olympus device (p<0.05). IPPS symptom improvement and complication rates were similar between groups. Patients in the Biolitec arm had more intraoperative bleeding episodes requiring conversion to monopolar transurethral resection of the prostate (TURP) (three vs. none). CONCLUSIONS: In a head-to-head randomized trial, Olympus Plasma Button transurethral vaporization was more cost-effective, faster, and preferred by surgical staff when compared to Biolitetec Diode Laser vaporization. Both devices showed similar safety and efficacy.

Study habits of Canadian urology residents: Implications for development of a competence by design curriculum.

INTRODUCTION: The purpose of this study was to evaluate the study habits of Canadian urology residents throughout their residency training. METHODS: A survey was administered to all final-year Canadian urology residents over a two-year period. Sixty-seven respondents answered a survey consisting of 54 questions scored on a 10-point Likert score. The survey addressed study habits throughout training, motivations for studying, and preferred resources used. RESULTS: Dedication to studying was directly correlated with proximity to the Royal College of Physicians and Surgeons of Canada (RCPSC) exam. Ninety-six percent of residents reported studying over 10 hours per week during their chief year compared to 0% during their junior year. As residents progressed in their training, preparation for the Royal College exam became the greatest motivator for studying. There was considerable variability in study methods and study resources used throughout training. In their chief year, residents found such resources as the textbook Campbell-Walsh, AUA updates, CUA and AUA guidelines, and the study notes of former trainees to be valuable for their preparation. Teaching rounds, journal clubs, and reading current urological literature were found to be les helpful. Forty-six percent of all residents surveyed indicated that they would prefer writing their RCPSC exam one year earlier than the current timing. CONCLUSIONS: This study provides insight into study habits of Canadian urology residents. This data may be helpful in shaping the future of urology training programs and examinations within Canada and elsewhere.

Serum follicle-stimulating hormone levels predict time to development of castration-resistant prostate cancer.

INTRODUCTION: Treatment of advancing prostate cancer focuses on blocking the activation of the androgen receptor with resultant prolonged perturbation of the hypothalamic-pituitary-gonadal axis. Androgen deprivation therapy (ADT) is marked, however, by eventual progression to castration- resistant prostate cancer (CRPC). Emerging evidence has postulated that follicle-stimulating hormone (FSH) may lead to proliferative and mutagenic responses of prostate cancer. We investigated the association of serum FSH and time to castration resistance. METHODS: This was a single-centre retrospective study assessing serum FSH levels of patients undergoing ADT for advancing prostate cancer. The primary outcome was time of ADT initiation to the development of CRPC. For each patient on treatment and with castrate levels of testosterone, the maximum FSH value between ADT commencement and CRPC was identified and recorded. FSH was analyzed as a continuous and categorical variable. Cox multivariate regression in a step-wise fashion was used to explore the association between FSH levels and time to CRPC. RESULTS: From a database of 323 prostate cancer patients actively managed with ADT, 103 men had a documented FSH value while castrate, with 45 men progressing to CRPC. The mean ± standard deviation maximum FSH value of these patients was 6.66 ± 4.22 mIU/mL (range: 1.5-28.1). The mean duration from ADT commencement to CRPC was 3.03 ± 0.34 years (range: 0.36-9.71). Univariate analysis suggested a trend of a negative correlation between FSH values and time to castrate resistance. A FSH value of less than or equal to the lowest tertile (4.8 mIU/mL) was associated with a longer time to CRPC (hazard ratio 0.46; p = 0.006). In the Cox regression analysis, elevated FSH was associated with a shorter duration time to CRPC (p = 0.03). CONCLUSIONS: This retrospective, single-centre study would suggest there may be an association between serum FSH levels and time to CRPC for men treated palliatively with ADT for advancing prostate cancer. Further clinical investigation in a larger cohort of men is required to determine any clinical utility of FSH as a biomarker of progression or target for therapy.

Impact of body mass index on clinical outcomes associated with percutaneous nephrolithotomy.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the preferred treatment for patients with large renal calculi or stones that have not responded to extracorporeal shock wave lithotripsy (ESWL). The objective of this study was to compare outcomes and complications of PCNL in patients of various body mass indices (BMI) to determine the safety of this procedure in patients with elevated BMI. METHODS: A retrospective chart review of 114 patients who underwent PCNL between 2006 and 2009 was performed. Patients were separated into 4 groups with respect to their BMI: (1) ideal body weight (BMI <25 kg/m(2)), (2) overweight (BMW 25-29 kg/m(2)), (3) obese (BMI 30-39 kg/m(2)) and (4) morbidly obese (BMI ≥40 kg/m(2)). One-way ANOVA and univariate logistic regression analysis were used to assess the association between BMI (classified into 4 levels) and variables including age, sex, stone size, length of stay, incidence of complications and stone-free rates. RESULTS: The distribution of the 114 patients in each BMI category was: ideal body weight 39 (34%), overweight 24 (21%), obese 41 (36%), morbidly obese 10 (9%). There was no difference in the composition of groups with respect to age, sex, pharmacologically treated comorbidities or stone size. Mean length of stay in days, intra- and postoperative complication rates were not statistically different. Stone-free rates showed no significant difference between groups: 90% ideal body weight; 87% overweight; 90% obese; 80% morbidly obese (p = 0.83). INTERPRETATION: Outcomes of PCNL were statistically independent of BMI. PCNL is a safe and efficacious treatment of stone disease in patients of all sizes.

Variables influencing the likelihood of cardiac dysrhythmias during extracorporeal shock wave lithotripsy.

INTRODUCTION: Extracorporeal shock wave lithotripsy (ESWL) is a safe and effective treatment of upper urinary tract calculi. While serious side effects are rare, transient cardiac dysrhythmias (CD) may be associated with ESWL. The exact etiology of these events, which are often unpredictable, is poorly understood. Awareness of CD during ESWL and identification of risk factors for developing them could help clinicians predict and manage them safely and effectively. The current study examines selected variables to determine whether they may predispose individuals to developing CD during ESWL. METHODS: We compared 16 patients who experienced CD during ESWL to 56 control patients. Cases and controls were compared with respect to several continuous and discrete variables, including age, pre-treatment heart rate, number of shocks received during treatment, energy setting of the lithotripter, gender, presence of a ureteric stent, previous ESWL and side being treated. RESULTS: Cardiac dysrhythmias occurred more frequently in younger patients and in those being treated for right-sided stones. The other variables did not influence the likelihood of CD. All CD resolved promptly following conversion to electrocardiogram (ECG)-gating. CONCLUSION: Younger age and right-sided treatment predisposed individuals to developing CD during ESWL. Careful ECG monitoring should be performed during treatment.

Urolithiasis in the elderly.

OBJECTIVES: Urolithiasis is an increasing problem in patients ≥ 80 years. Our objective was to compare patients ≥ 80 years with urolithiasis to a younger cohort in terms of presentation and management. METHODS: Patients referred to a tertiary care stone clinic for management of urolithiasis over a 5 year period were reviewed. Data collected on clinical parameters for patients ≥ 80 years were compared with a random sample of those < 80 years. RESULTS: There were 26 patients ≥ 80 years and 102 in the sample < 80 years; mean age was 83.5 ± 0.6 and 50.1 ± 1.3 years, respectively. The older group had more comorbidities. The presenting complaint was more often flank pain in younger patients. Patients ≥ 80 years had larger stones. Early ureteric stent insertion was more likely in the elderly compared with the younger group (27% versus 7%, p < 0.01). Definitive therapy for patients ≥ 80 years was most often percutaneous nephrolithotomy (PCNL) (23%) compared with only 9% in the younger group. In contrast, the most common definitive treatment modality used for patients < 80 years was extracorporeal shock wave lithotripsy (ESWL) (35% versus 8%, p < 0.01). There was no difference in intraoperative complications. Thirty nine percent of the older group was managed as outpatients. More of the older group had postoperative complications but all were minor. CONCLUSION: Urolithiasis in the elderly is challenging to treat because they have more comorbidities and are less likely to present with classic symptoms of renal colic. This may lead to later presentation with larger and more complex stone disease. Early ureteric stent is often required and definitive PCNL is more likely than in the younger cohort. Despite these issues most can be treated safely and often as an outpatient.

Fenretinide promotes functional recovery and tissue protection after spinal cord contusion injury in mice.

The inflammatory response is thought to contribute to secondary damage after spinal cord injury (SCI). Polyunsaturated fatty acids (PUFAs) play an important role in the onset and resolution of inflammation. Arachidonic acid (AA), an omega-6 PUFA, contributes to the initiation of inflammatory responses, whereas docosahexaenoic acid (DHA), an omega-3 PUFA, has antiinflammatory effects. Therefore, decreasing AA and increasing DHA levels after SCI might be expected to attenuate inflammation after SCI and promote tissue protection and functional recovery. We show here that daily oral administration of fenretinide after spinal cord contusion injury led to a significant decrease in AA and an increase in DHA levels in plasma and injured spinal cord tissue. This was accompanied by a significant reduction in tissue damage and improvement in locomotor recovery. Fenretinide also reduced the expression of proinflammatory genes and the levels of oxidative stress markers after SCI. In addition, in vitro studies demonstrated that fenretinide reduced TNF-alpha (tumor necrosis factor-alpha) expression by reactive microglia. These results demonstrate that fenretinide treatment after SCI can reduce inflammation and tissue damage in the spinal cord and improve locomotor recovery. These beneficial effects may be mediated via the ability of fenretinide to modulate PUFA homeostasis. Since fenretinide is currently in clinical trials for the treatment of cancers, this drug might be a good candidate for the treatment of acute SCI in humans.

Fenretinide corrects newly found ceramide deficiency in cystic fibrosis.

Chronic and persistent lung infections cause the majority of morbidity and mortality in patients with cystic fibrosis (CF). Galactosyl ceramide has been previously shown to be involved in Pseudomonas internalization. Therefore, we assessed ceramide levels in the plasma of patients with CF and compared them to healthy volunteers using high-performance liquid chromatography followed by mass spectrometry. Our results demonstrate that patients with CF display significantly lower levels of several ceramide sphingolipid species, specifically C14:0, C20:1, C22:0, C22:1, and C24:0 ceramides, and dihydroxy ceramide (DHC16:0). We report that Cftr-knockout mice display diminished ceramide levels in CF-related organs (lung, pancreas, ileum, and plasma) compared with their littermate controls. Since it has been previously reported that in vitro treatment with fenretinide induced ceramide in neuroblastoma cell lines, we decided to test this drug in vivo using our Cftr-knockout mice in an attempt to correct this newly identified defect in ceramide levels. We demonstrate that treatment with fenretinide is able to increase ceramide concentrations in CF-related organs. We further assessed the biological effect of fenretinide on the ability of Cftr-knockout mice to combat lung infection with P. aeruginosa. Our data show dramatic improvement in the ability of Cftr-knockout mice to control P. aeruginosa infection. Overall, these findings not only document a novel deficiency in several ceramide species in patients with CF, but also demonstrate a pharmacologic means to correct this defect in Cftr-knockout mice. Our data provide a strong rationale for clinical intervention that may benefit patients with CF suffering from CF lung disease.