Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation an... more Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon’s enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditi...
Renal transplantation is the preferred treatment for patients with end-stage renal disease. The c... more Renal transplantation is the preferred treatment for patients with end-stage renal disease. The current gold standard of kidney preservation for transplantation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal ischemia-reperfusion injury (IRI), a pathological process that negatively impacts graft survival and function. Recent efforts to mitigate cold renal IRI involve preserving renal grafts at higher or subnormothermic temperatures. These temperatures may be beneficial in reducing the risk of cold renal IRI, while also maintaining active biological processes such as increasing the expression of mitochondrial protective metabolites. In this review, we discuss different preservation temperatures for renal transplantation and pharmacological supplementation of kidney preservation solutions with hydrogen sulfide to determine an optimal preservation temperature to mitigate cold renal IRI and enhance renal graft function and recipient survival.
Canadian survey on the rates of use of intraoperative diuretics and justification for their use d... more Canadian survey on the rates of use of intraoperative diuretics and justification for their use during renal allograft reperfusion Background: Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons. Methods: An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ 2 analysis to assess the relationship between demographic factors and survey responses. Results: Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial. Conclusion: Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery. Contexte : On a utilisé le mannitol et le furosémide comme diurétiques peropératoires pour stimuler le fonctionnement précoce de l'allogreffe rénale et réduire le retard de fonctionnement du greffon. Comme les données probantes quant à l'efficacité de ces agents sont limitées, nous avons voulu caractériser l'utilisation des diurétiques chez les chirurgiens qui effectuent ces transplantations. Méthodes : Un sondage anonyme en ligne a été envoyé à tous les programmes de greffe canadiens où des greffes rénales sont couramment effectuées. Les questions avaient trait à l'utilisation et aux indications du mannitol et du furosémide. Les réponses ont été recueillies et analysées sous forme de nombres et de pourcentages des répondants. Le test du χ 2 a été utilisé pour évaluer le lien entre les facteurs démographiques et les réponses au sondage. Résultats : Trente-cinq chirurgiens ont répondu au sondage (taux de réponse 50 %). Soixante-dix pour cent des répondants ont indiqué effectuer annuellement 26 greffes ou plus, 88 % avaient suivi une spécialisation formelle pour l'exécution des greffes et 67 % ont dit être en cours de spécialisation. Seulement 24 % et 12 % respectivement ont dit croire que le mannitol et le furosémide permettent de réduire le retard de fonctionnement du greffon. Toutefois, 73 % et 53 % respectivement administraient de routine du mannitol et du furosémide aux patients. La justification la plus fréquente de l'utilisation du mannitol était d'induire la diurèse (54 %); 37 % des répondants ont dit utiliser le mannitol parce que c'est ce qu'on leur a enseigné durant leur formation. De même, 57 % utilisaient le furosémide pour la diurèse, dont 23 % disaient que c'est ce qu'on leur avait enseigné durant leur formation. Aucun lien n'est ressorti entre la
Introduction: The purpose of this study was to document the variability of faculty surgeon electr... more Introduction: The purpose of this study was to document the variability of faculty surgeon electrodermal activity (EDA) peaks during laparoscopic donor nephrectomy (LDN) to determine the effect of case difficulty and learner expertise on the stress response. Methods: EDA for a single faculty surgeon was captured over 15 LDN cases using an Empatica E4 wristband. During each case, one of three transplant fellows (novice, intermediate, or expert level LDN expertise) participated. Difficulty was rated preoperatively as “low/moderate/high” by the faculty. EDA peaks were collected and analyzed; the frequency and magnitude of EDA peaks, case difficulty, and fellow expertise were compared using a two-way factorial ANOVA. Results: The main effects of learner expertise (F[2, 308]=11.27, p<0.001) and difficulty rating (F[2, 414]=15.13, p<0.001) were significant. The interaction between difficulty and expertise on faculty EDA peaks was also significant (F[3, 391]=14.29, p<0.001). The n...
Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions mi... more Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. Methods: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 C, 22 C, and 37 C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 C. Results: Compared with all other groups, 22 C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 C was the optimal temperature to minimize hemorrhage and blood clots. Conclusion: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions.
Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive m... more Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive mCRPC. PSA declined by >[50% in 38% of patients. The best PSA response rate occurred after 3 cycles. Updated data will be provided at the time of the conference.
To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with p... more To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged ∼1 wk ( n = 5) and ∼6 wk ( n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 ± 7.3 (SD) mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 1-wk-old lambs and by 9.1 ± 3.2 mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the fir...
Canadian journal of surgery. Journal canadien de chirurgie, Jan 24, 2018
Kidney paired donation (KPD) programs are an effort to bridge the disparity between kidney supply... more Kidney paired donation (KPD) programs are an effort to bridge the disparity between kidney supply and demand. These programs combine several incompatible donor-recipient pairs in a national paired exchange database, thereby increasing the number of compatible matches. But KPD programs face unique challenges, particularly the large distances that often separate donors and recipients. Here we discuss key factors to consider when transitioning from a donor travelling model to a kidney shipment model in the Canadian context.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 24, 2018
Few transplant programs use kidneys from donors with body weight (BW) <10 kg. We hypothesized ... more Few transplant programs use kidneys from donors with body weight (BW) <10 kg. We hypothesized that pediatric en bloc transplants from donors with BW <10 kg, would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N=28). Data were stratified by smaller (donor BW less than 10 kg) (N=11) or larger donors (BW greater than 10 kg) (N=17). Renal volume was assessed during follow-up by ultrasound. Demographic characteristics were similar between the two groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1d post-transplant mean total renal volume in the smaller group was 28 ± 9 mm vs. 45 ± 12 mm (P <0.01). By 3 weeks, it was 53±19mm (smaller donors) vs. 73±19mm (larger donors) (P = NS). Complication rates ...
Canadian journal of surgery. Journal canadien de chirurgie, 2017
Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death ... more Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death (DCD) donor organs have traditionally been considered of inferior quality owing to warm ischemia experienced during procurement. We present, to our knowledge, the first analysis of simultaneous pancreas and kidney (SPK) transplants using DCD donor organs in Canada. We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68 NDD donors performed between October 2008 and July 2016. In all patients immunosuppression was induced with thymoglobulin and continued with tacrolimus, mycophenolate mofetil and prednisone maintenance therapy. Donor and recipient characteristics of DCD and NDD groups were similar with respect to age, sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours. Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for the DCD a...
Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascul... more Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascular complications such as thrombosis and kinking. Retroperitoneal compartment syndrome (RACS) is an under-recognized vascular cause of EAD with potentially devastating consequences, and may even result in a lost graft. The graft can be salvaged with early recognition and intervention through a mesh hood fascial closure (MHFC) technique. METHODS: Here we describe, in video, a 23-years-old male recipient diagnosed with renal failure secondary to chronic reflux. He has a 6 months history of peritoneal dialysis and is currently on hemodialysis. The patient received an anonymous living-donor right kidney from our paired exchange program. His BMI is 22. The graft had a single renal artery and single renal vein. A standard anastomosis was performed and subsequent urine output was brisk. The fascia was closed without tension. However, urine production ceased after the fascia was fully closed. A case of RACS was suspected and intraoperative Doppler ultrasound showed no blood flow in the graft. Immediately re-exploration revealed the graft to be abnormal in color and turgor. RESULTS: These abnormalities resolved after pressure was relieved. The kidney was then placed in the optimal position within the iliac fossa and a large ellipsoid piece of polypropylene mesh was draped loosely and without tension over the graft. The mesh was attached to the posterior fascial edges using interrupted #1 polypropylene sutures. Skin closure then was completed over a closed suction drain placed in the retroperitoneal space lateral to the kidney. Doppler ultrasound after skin closure showed good flow and the postoperative course was unremarkable. CONCLUSIONS: RACS could be associated with small android pelvis and lack of compliance in the retroperitoneal cavity secondary to peritoneal dialysis. Suspected RACS require prompt intervention to prevent irreversible graft dysfunction. We have shown that MHFC is an effective and safe method to treat EAD secondary to RACS.
operation or history of acute rejection postoperatively. Preoperative MAG3 clearance of the remai... more operation or history of acute rejection postoperatively. Preoperative MAG3 clearance of the remaining and transplanted kidneys were almost equal, 157AE34 ml/min and 156AE35 ml/min respectively. The measuring method of MAG3 clearance used RUNQ (Renal Uptake New Quantitative method) mood. Analyzed factors were dialysis period, height, body weight, graft weight, body mass index, and surface of the body area. RESULTS: Preoperative MAG3 clearance of remaining kidney and transplanted kidney negatively correlated with donor age (P 0.001), and we can confirm the regular decline of the kidney function with the aging in MAG3 clearance. Postoperative MAG3 clearance of remaining kidney and transplanted kidney significantly increased compared with that of pre-transplantation, 242AE51 ml/min and 236AE57 ml/min respectively (P 0.001), though there is no difference in the ERPF increase rate between donor and recipient, 58.5AE40 % and 55.6AE38 % respectively (P¼0.649). There are significant factors correlated with increasing rate of graft compensatory hypertrophy in MAG3 clearance, which are the height ratio between donor and recipient (P¼0.003), the weight of graft (P¼0.01), and preoperative ERPF of transplanted kidney (P¼0.002). On the other hand, body weight, WIT, and dialysis period were not significant. CONCLUSIONS: In conclusion, the compensatory hypertrophy ratio (increasing rate of the ERPF) in a transplanted kidney correlates with the graft weight and preoperative ERPF of the transplanted kidney. It is also prescribed by the physique difference between donor and recipient. There was no difference in the ERPF increase rate between donor and recipient.
Introduction: We compared the outcomes of single-incision, robotassisted laparoscopic pyeloplasty... more Introduction: We compared the outcomes of single-incision, robotassisted laparoscopic pyeloplasty vs. multiple-incision pyeloplasty using the da Vinci robotic system.Methods: We reviewed all consecutive robotic pyeloplasties by a single surgeon from January 2011 to August 2015. A total of 30 procedures were performed (16 single:14 multi-port). Two different single-port devices were compared: the GelPort (Applied Medical, Rancho Santa Margarita, CA) and the Intuitive single-site access port (Intuitive Surgical, Sunnyvale, CA).Results: Patient demographics were similar between the two groups. Mean operating time was similar among the single and multi-port groups (225.2 min vs. 198.9 minutes [p=0.33]). There was no significant difference in length of hospital stay in either group (86.2 hr vs. 93.2 hr [p=0.76]). There was no difference in success rates or postoperative complications among groups.Conclusions: Single-port robotic pyeloplasty is non-inferior to multiple-incision robotic su...
Transplant international : official journal of the European Society for Organ Transplantation, Jan 20, 2016
Our objective was to define optimal management of distal ureteric strictures following renal tran... more Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Amongst primary treatments (n=303), the open approach had 85.4% success (95% CI 72.5-93.1) and the endourological approach had 64.3% success (95% CI 58.3-69.9). Amongst secondary treatments (n=82), the open approach had 93.1% success (95% CI 77.0-99.2) and the endourological approach had 75.5% success (95% CI 62.3-85.2). The most common primary open treatment was ureteric reimplantation (n=33, 81.8% success, 95% CI 65.2-91.8). The most common primary endourological treatment was dilation (n=133, 58.6% success, 95% CI 50.1-66.7). Fourteen complications, including death (4 weeks post-op) and graft loss (12 days post-op), followed endourological treatment. One complicati...
Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, r... more Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H 2 S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H 2 S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H 2 Sspecific probe MeRhoAz, it was found that H 2 S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H 2 S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H 2 S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H 2 S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.
American journal of physiology. Regulatory, integrative and comparative physiology, 2002
The present experiments were carried out to investigate the role of endogenously produced NO in m... more The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged approximately 1 (n = 8) and approximately 6 wk (n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME; experiment 1) or its inactive isomer D-NAME (experiment 2). After administration of L-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by approximately 50% at 20 min, remaining decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after L-NAME. Proximal fractional Na(+) reabsorption decreased after L-NAME administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was sustained for 60 min. There were no effects of L-NAME on proximal f...
Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation an... more Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon’s enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditi...
Renal transplantation is the preferred treatment for patients with end-stage renal disease. The c... more Renal transplantation is the preferred treatment for patients with end-stage renal disease. The current gold standard of kidney preservation for transplantation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal ischemia-reperfusion injury (IRI), a pathological process that negatively impacts graft survival and function. Recent efforts to mitigate cold renal IRI involve preserving renal grafts at higher or subnormothermic temperatures. These temperatures may be beneficial in reducing the risk of cold renal IRI, while also maintaining active biological processes such as increasing the expression of mitochondrial protective metabolites. In this review, we discuss different preservation temperatures for renal transplantation and pharmacological supplementation of kidney preservation solutions with hydrogen sulfide to determine an optimal preservation temperature to mitigate cold renal IRI and enhance renal graft function and recipient survival.
Canadian survey on the rates of use of intraoperative diuretics and justification for their use d... more Canadian survey on the rates of use of intraoperative diuretics and justification for their use during renal allograft reperfusion Background: Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons. Methods: An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ 2 analysis to assess the relationship between demographic factors and survey responses. Results: Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial. Conclusion: Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery. Contexte : On a utilisé le mannitol et le furosémide comme diurétiques peropératoires pour stimuler le fonctionnement précoce de l'allogreffe rénale et réduire le retard de fonctionnement du greffon. Comme les données probantes quant à l'efficacité de ces agents sont limitées, nous avons voulu caractériser l'utilisation des diurétiques chez les chirurgiens qui effectuent ces transplantations. Méthodes : Un sondage anonyme en ligne a été envoyé à tous les programmes de greffe canadiens où des greffes rénales sont couramment effectuées. Les questions avaient trait à l'utilisation et aux indications du mannitol et du furosémide. Les réponses ont été recueillies et analysées sous forme de nombres et de pourcentages des répondants. Le test du χ 2 a été utilisé pour évaluer le lien entre les facteurs démographiques et les réponses au sondage. Résultats : Trente-cinq chirurgiens ont répondu au sondage (taux de réponse 50 %). Soixante-dix pour cent des répondants ont indiqué effectuer annuellement 26 greffes ou plus, 88 % avaient suivi une spécialisation formelle pour l'exécution des greffes et 67 % ont dit être en cours de spécialisation. Seulement 24 % et 12 % respectivement ont dit croire que le mannitol et le furosémide permettent de réduire le retard de fonctionnement du greffon. Toutefois, 73 % et 53 % respectivement administraient de routine du mannitol et du furosémide aux patients. La justification la plus fréquente de l'utilisation du mannitol était d'induire la diurèse (54 %); 37 % des répondants ont dit utiliser le mannitol parce que c'est ce qu'on leur a enseigné durant leur formation. De même, 57 % utilisaient le furosémide pour la diurèse, dont 23 % disaient que c'est ce qu'on leur avait enseigné durant leur formation. Aucun lien n'est ressorti entre la
Introduction: The purpose of this study was to document the variability of faculty surgeon electr... more Introduction: The purpose of this study was to document the variability of faculty surgeon electrodermal activity (EDA) peaks during laparoscopic donor nephrectomy (LDN) to determine the effect of case difficulty and learner expertise on the stress response. Methods: EDA for a single faculty surgeon was captured over 15 LDN cases using an Empatica E4 wristband. During each case, one of three transplant fellows (novice, intermediate, or expert level LDN expertise) participated. Difficulty was rated preoperatively as “low/moderate/high” by the faculty. EDA peaks were collected and analyzed; the frequency and magnitude of EDA peaks, case difficulty, and fellow expertise were compared using a two-way factorial ANOVA. Results: The main effects of learner expertise (F[2, 308]=11.27, p<0.001) and difficulty rating (F[2, 414]=15.13, p<0.001) were significant. The interaction between difficulty and expertise on faculty EDA peaks was also significant (F[3, 391]=14.29, p<0.001). The n...
Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions mi... more Introduction: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. Methods: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 C, 22 C, and 37 C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 C. Results: Compared with all other groups, 22 C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 C was the optimal temperature to minimize hemorrhage and blood clots. Conclusion: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions.
Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive m... more Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive mCRPC. PSA declined by >[50% in 38% of patients. The best PSA response rate occurred after 3 cycles. Updated data will be provided at the time of the conference.
To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with p... more To test the hypothesis that acetylcholine-induced relaxation of the renal artery decreases with postnatal age, we measured parameters of renal hemodynamics before and for 35 s after aortic suprarenal injection of acetylcholine in conscious, chronically instrumented lambs aged ∼1 wk ( n = 5) and ∼6 wk ( n = 5). Acetylcholine was administered in one of five doses ranging from 0 to 10 mg/kg body wt; doses were administered randomly, in the same volume. There were significant age- and dose-dependent changes in renal vascular resistance after acetylcholine administration, such that the response was greater in 1-wk-old lambs. After the highest dose tested, renal vascular resistance decreased by 13.6 ± 7.3 (SD) mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 1-wk-old lambs and by 9.1 ± 3.2 mmHg ⋅ ml−1 ⋅ min ⋅ g kidney wt in 6-wk-old lambs at 35 s. We also observed a transient renal vasoconstriction before the renal vasodilatation in 6-wk-old lambs but not in 1-wk-old animals. These data provide the fir...
Canadian journal of surgery. Journal canadien de chirurgie, Jan 24, 2018
Kidney paired donation (KPD) programs are an effort to bridge the disparity between kidney supply... more Kidney paired donation (KPD) programs are an effort to bridge the disparity between kidney supply and demand. These programs combine several incompatible donor-recipient pairs in a national paired exchange database, thereby increasing the number of compatible matches. But KPD programs face unique challenges, particularly the large distances that often separate donors and recipients. Here we discuss key factors to consider when transitioning from a donor travelling model to a kidney shipment model in the Canadian context.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jan 24, 2018
Few transplant programs use kidneys from donors with body weight (BW) <10 kg. We hypothesized ... more Few transplant programs use kidneys from donors with body weight (BW) <10 kg. We hypothesized that pediatric en bloc transplants from donors with BW <10 kg, would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N=28). Data were stratified by smaller (donor BW less than 10 kg) (N=11) or larger donors (BW greater than 10 kg) (N=17). Renal volume was assessed during follow-up by ultrasound. Demographic characteristics were similar between the two groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1d post-transplant mean total renal volume in the smaller group was 28 ± 9 mm vs. 45 ± 12 mm (P <0.01). By 3 weeks, it was 53±19mm (smaller donors) vs. 73±19mm (larger donors) (P = NS). Complication rates ...
Canadian journal of surgery. Journal canadien de chirurgie, 2017
Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death ... more Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death (DCD) donor organs have traditionally been considered of inferior quality owing to warm ischemia experienced during procurement. We present, to our knowledge, the first analysis of simultaneous pancreas and kidney (SPK) transplants using DCD donor organs in Canada. We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68 NDD donors performed between October 2008 and July 2016. In all patients immunosuppression was induced with thymoglobulin and continued with tacrolimus, mycophenolate mofetil and prednisone maintenance therapy. Donor and recipient characteristics of DCD and NDD groups were similar with respect to age, sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours. Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for the DCD a...
Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascul... more Early allograft dysfunction (EAD) can be caused by a number of technical factors including vascular complications such as thrombosis and kinking. Retroperitoneal compartment syndrome (RACS) is an under-recognized vascular cause of EAD with potentially devastating consequences, and may even result in a lost graft. The graft can be salvaged with early recognition and intervention through a mesh hood fascial closure (MHFC) technique. METHODS: Here we describe, in video, a 23-years-old male recipient diagnosed with renal failure secondary to chronic reflux. He has a 6 months history of peritoneal dialysis and is currently on hemodialysis. The patient received an anonymous living-donor right kidney from our paired exchange program. His BMI is 22. The graft had a single renal artery and single renal vein. A standard anastomosis was performed and subsequent urine output was brisk. The fascia was closed without tension. However, urine production ceased after the fascia was fully closed. A case of RACS was suspected and intraoperative Doppler ultrasound showed no blood flow in the graft. Immediately re-exploration revealed the graft to be abnormal in color and turgor. RESULTS: These abnormalities resolved after pressure was relieved. The kidney was then placed in the optimal position within the iliac fossa and a large ellipsoid piece of polypropylene mesh was draped loosely and without tension over the graft. The mesh was attached to the posterior fascial edges using interrupted #1 polypropylene sutures. Skin closure then was completed over a closed suction drain placed in the retroperitoneal space lateral to the kidney. Doppler ultrasound after skin closure showed good flow and the postoperative course was unremarkable. CONCLUSIONS: RACS could be associated with small android pelvis and lack of compliance in the retroperitoneal cavity secondary to peritoneal dialysis. Suspected RACS require prompt intervention to prevent irreversible graft dysfunction. We have shown that MHFC is an effective and safe method to treat EAD secondary to RACS.
operation or history of acute rejection postoperatively. Preoperative MAG3 clearance of the remai... more operation or history of acute rejection postoperatively. Preoperative MAG3 clearance of the remaining and transplanted kidneys were almost equal, 157AE34 ml/min and 156AE35 ml/min respectively. The measuring method of MAG3 clearance used RUNQ (Renal Uptake New Quantitative method) mood. Analyzed factors were dialysis period, height, body weight, graft weight, body mass index, and surface of the body area. RESULTS: Preoperative MAG3 clearance of remaining kidney and transplanted kidney negatively correlated with donor age (P 0.001), and we can confirm the regular decline of the kidney function with the aging in MAG3 clearance. Postoperative MAG3 clearance of remaining kidney and transplanted kidney significantly increased compared with that of pre-transplantation, 242AE51 ml/min and 236AE57 ml/min respectively (P 0.001), though there is no difference in the ERPF increase rate between donor and recipient, 58.5AE40 % and 55.6AE38 % respectively (P¼0.649). There are significant factors correlated with increasing rate of graft compensatory hypertrophy in MAG3 clearance, which are the height ratio between donor and recipient (P¼0.003), the weight of graft (P¼0.01), and preoperative ERPF of transplanted kidney (P¼0.002). On the other hand, body weight, WIT, and dialysis period were not significant. CONCLUSIONS: In conclusion, the compensatory hypertrophy ratio (increasing rate of the ERPF) in a transplanted kidney correlates with the graft weight and preoperative ERPF of the transplanted kidney. It is also prescribed by the physique difference between donor and recipient. There was no difference in the ERPF increase rate between donor and recipient.
Introduction: We compared the outcomes of single-incision, robotassisted laparoscopic pyeloplasty... more Introduction: We compared the outcomes of single-incision, robotassisted laparoscopic pyeloplasty vs. multiple-incision pyeloplasty using the da Vinci robotic system.Methods: We reviewed all consecutive robotic pyeloplasties by a single surgeon from January 2011 to August 2015. A total of 30 procedures were performed (16 single:14 multi-port). Two different single-port devices were compared: the GelPort (Applied Medical, Rancho Santa Margarita, CA) and the Intuitive single-site access port (Intuitive Surgical, Sunnyvale, CA).Results: Patient demographics were similar between the two groups. Mean operating time was similar among the single and multi-port groups (225.2 min vs. 198.9 minutes [p=0.33]). There was no significant difference in length of hospital stay in either group (86.2 hr vs. 93.2 hr [p=0.76]). There was no difference in success rates or postoperative complications among groups.Conclusions: Single-port robotic pyeloplasty is non-inferior to multiple-incision robotic su...
Transplant international : official journal of the European Society for Organ Transplantation, Jan 20, 2016
Our objective was to define optimal management of distal ureteric strictures following renal tran... more Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Amongst primary treatments (n=303), the open approach had 85.4% success (95% CI 72.5-93.1) and the endourological approach had 64.3% success (95% CI 58.3-69.9). Amongst secondary treatments (n=82), the open approach had 93.1% success (95% CI 77.0-99.2) and the endourological approach had 75.5% success (95% CI 62.3-85.2). The most common primary open treatment was ureteric reimplantation (n=33, 81.8% success, 95% CI 65.2-91.8). The most common primary endourological treatment was dilation (n=133, 58.6% success, 95% CI 50.1-66.7). Fourteen complications, including death (4 weeks post-op) and graft loss (12 days post-op), followed endourological treatment. One complicati...
Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, r... more Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H 2 S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H 2 S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H 2 Sspecific probe MeRhoAz, it was found that H 2 S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H 2 S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H 2 S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H 2 S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.
American journal of physiology. Regulatory, integrative and comparative physiology, 2002
The present experiments were carried out to investigate the role of endogenously produced NO in m... more The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged approximately 1 (n = 8) and approximately 6 wk (n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME; experiment 1) or its inactive isomer D-NAME (experiment 2). After administration of L-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by approximately 50% at 20 min, remaining decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after L-NAME. Proximal fractional Na(+) reabsorption decreased after L-NAME administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was sustained for 60 min. There were no effects of L-NAME on proximal f...
Uploads
Papers by Alp Sener