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Background: Liver ischemia reperfusion injury (LIRI) often occurs during liver transplantation, resection, and various circulatory shock procedures, leading to severe metabolic disorders, inflammatory immune responses, oxidative stress injury, and cell apoptosis. Methyl eugenol (ME) is structurally similar to eugenol and has anti-inflammatory and apoptotic pharmacological effects. However, whether ME protects the liver from LIRI damage requires further investigation., Methods: We established a partially warm LIRI model by subjecting C57BL/6J mice to 60 min of ischemia, followed by reperfusion for 6 h. We also established a hypoxia-reoxygenation injury (H/R) cell model by subjecting AML12 (a mouse liver cell line) cells to 24 h hypoxia, followed by 18 h normoxia. The extent of liver injury was assessed by serum transaminase concentrations, hematoxylin and eosin staining, quantitative real-time PCR, myeloperoxidase activity, and TUNEL analysis. Apoptosis was detected using flow cytometry. The protein levels of p-PI3K, PI3K, p-Akt, Akt, p-Bad, Bad, Bcl-2, Bax, and cleaved caspase-3 were detected by western blotting. LY294002, an inhibitor of PI3K/Akt signaling, was used to elucidate the relationship between ME and PI3K/Akt signaling., Results: ME successfully alleviated LIRI-induced liver injury, inflammatory response, and apoptosis induced, as well as liver cell injury induced by hypoxia reoxygenation. ME is known to activate the PI3K/Akt signaling pathway in hepatocyte injury in vivo and in vitro, and when this signaling pathway is inhibited, the protective effect of ME is abrogated., Conclusions: The use of ME is a potential therapeutic approach for regulating LIRI by activating PI3K/Akt signaling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the learning curve of robotic-assisted partial nephrectomy as it pertains to operative time (OT) and advanced perioperative variables such as achievement of trifecta, postoperative complications, 30-day readmission rates (RR), warm ischemia time (WIT), and functional volume loss (FVL)., Methods: We evaluated 418 consecutive robotic-assisted partial nephrectomy performed by a single surgeon between February 2008 and April 2019. Multivariable log-log regression models were used to evaluate the associations between case number and continuous outcomes (OT, WIT, and FVL). Multivariable logistic regression models were used to evaluate the association of case number with dichotomous outcomes (trifecta, postoperative complications, RR)., Results: Among the 406 eligible patients included in the study, 252 (62.1%) were male, median age was 63 years (range, 22-84), and median body mass index was 29 kg/m 2 (interquartile range 26-33). Surgeon experience was associated with shorter OT (-2.5% per 50% increase in case number; 95% confidence interval; P <.001) and plateaus around 77 cases performed. There was slight improvement with trifecta (odds ratio [per 50% increase in cases] = 1.08; 95% confidence interval) and the plateau was also at 77 cases, however, this was not statistically significant (P = .086). We did not find statistically significant associations of surgeon experience with FVL (P = .77), postoperative complications (P = .74), WIT (P = .73), or 30-day RR (P = .33)., Conclusion: There does not appear to be a relationship between surgical experience and grade 3 or higher postoperative complications, 30-day RR, WIT, or FVL. Trifecta outcomes and maximum OT performance appear to be optimized at approximately 77 cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: The optimal ischemia technique at partial nephrectomy (PN) for renal masses is yet to be determined., Objective: To summarize and analyze the current evidence about surgical, oncological, and functional outcomes after different ischemia techniques (cold, warm, and zero ischemia) at PN., Evidence Acquisition: A computerized systematic literature search was performed by using PubMed (MEDLINE) and Science Direct. Identification and selection of the studies were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were estimated blood loss (EBL), overall complications, positive surgical margins, local tumor recurrence, and renal function preservation. Meta-analysis and forest-plot diagrams were performed. Overall pooled estimates, together with 95% confidence intervals (CIs), of the incidence of all parameters were obtained using a random effect model (RE-Model) on the log transformed means (MLN), proportion, or standardized mean change, as deemed appropriate., Evidence Synthesis: One hundred and fifty-six studies were included. No clinically meaningful differences were found in terms of EBL after cold (mean: 215.5; 95% CI: 154.2-276.8m), warm (mean: 201.8; 95% CI: 175.0-228.7ml), or zero (mean: 261.2; 95% CI: 171.0-351.3ml) ischemia technique. Overall, postoperative complications were recorded in 14.1% (95% CI: 6.7-27.4), 11.1% (95% CI: 10.0-12.3), and 9.7% (95% CI: 7.7-12.2) of patients after cold, warm, and zero ischemia (p<0.01), respectively. Positive surgical margins were recorded in 4.8% (95% CI: 1.9-10.9), 4.0% (95% CI: 3.4-4.8), and 5.6% (95% CI: 3.1-9.8) of patients after cold, warm, and zero ischemia (p<0.01), respectively. Local recurrence was recorded in 3.2% (95% CI: 1.9-5.2) and 3.1% (95% CI: 0.7-11.5) of patients after warm and zero ischemia (p<0.01), respectively. The log 2 of estimated glomerular filtration ratio mean changes were-1.37 (95% CI:-3.42 to 0.68),-1.00 (-2.04 to 0.03), and-0.71 (-1.15 to-0.27) ml/min after cold, warm, and zero ischemia, respectively. Low level of evidence, retrospective nature of most of included studies, a high risk of selection bias, and heterogeneity within included studies limited the overall quality of the analysis., Conclusions: The effect of ischemia technique at PN is still debatable and subject to confounding by several factors, namely, patients' selection criteria, surgical technique used, and percentage of functional parenchyma spared during surgery. These confounders bias available evidence and were addressed by only a small part of available studies. Unfortunately, the overall quality of literature evidences and the high risk of selection bias limit the possibility of any causal interpretation about the relationship between the ischemia technique used and surgical, oncological, or functional outcomes. Thus, none of the available ischemia technique could be recommended over the other., Patient Summary: The present analysis shows that none of the available ischemia techniques, namely, cold, warm, or zero ischemia, is universally superior to the others, and other factors play a role in the surgical outcome., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To explore whether variation of warm ischemia time (WIT) is associated with functional and perioperative outcomes following robotic partial nephrectomy (RPN)., Materials and Methods: Six hundred sixty eight patients, each with 2 kidneys, undergoing RPNs for a cT1 tumor were identified from a U.S. multi-institutional database. The associations between WIT, normal excisional volume loss (EVL), and surgical and renal function outcomes, including acute kidney injury at discharge and percent change in eGFR at up to 24 months post-RPN, were evaluated using Spearman's rank correlation test as well as multivariable models controlling for tumor, surgeon, and patient characteristics., Results: WIT was weakly correlated with EVL (r = 0.32, P < .001), blood loss (r = 0.34, P < .001), and length of stay (r = 0.35, P < .001). WIT was found to be significantly associated with acute kidney injury at discharge (odds ratio = 6.23; confidence interval 1.52, 30.39). Extended WIT was not found to be significantly associated with renal function decline at 1 year post RPN (P > .05)., Conclusion: Extended WIT is associated with worse perioperative outcomes. While controlling for tumor size and EVL, effects on short-term renal function were still seen after as short as 20 minutes. Efforts to limit warm ischemia time should continue to be implemented during RPN to maximize postoperative renal function., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To externally validate the Spectrum Score (SS) using a modified calculation based on functional parenchymal volumes (FPVs) instead of renal scans. The SS quantifies acute ischemic injury in the ipsilateral kidney after partial nephrectomy. However, this metric requires renal split function assessment via renal scans, which may be unavailable in routine practice., Methods: We retrospectively reviewed patients with a solitary renal mass and contralateral kidney who underwent partial nephrectomy at our institution between 2015 and 2017. FPVs were calculated using cylindrical volume approximation and used to quantitate relative renal function. Based on renal split function and parenchyma preserved, we determined creatinine ideal , assuming no ipsilateral kidney ischemic injury, and creatinine worst-case , assuming temporary ipsilateral kidney nonfunction. FPV-based SS was defined as follows: (observed peak creatinine-creatinine ideal )/(creatinine worst-case -creatinine ideal ). Functional recovery was defined as follows: (% function saved)/(% parenchyma preserved). Factors associated with FPV-based SS and functional recovery were assessed using linear regression., Results: We assessed 174 patients with a median renal mass size of 2.7 cm (IQR 2.0-3.6), warm ischemia time of 26.0 minutes (IQR 19.0-34.3), and parenchyma preservation of 92.6% (IQR 80.8-100). Preoperative ipsilateral kidney % split function (P = .003), preoperative ipsilateral kidney glomerular filtration rate (P = .045), and warm ischemia time (P = .005) were independently associated with FPV-based SS. Only FPV-based SS (P<.001) was independently associated with functional recovery., Conclusion: The FPV-based SS, which does not require renal scans, quantifies acute ipsilateral renal dysfunction and predicts functional recovery after partial nephrectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Fatty liver is one of the widely accepted marginal donor for liver transplantation, but is also more sensitive to ischemia and reperfusion injury (IRI) and produces more reactive oxygen species (ROS). Moreover, so far, no effective method has been developed to alleviate it. Endoplasmic reticulum stress (ER-stress) of hepatocyte is associated with the occurrence of fatty liver disease, but ER-stress of kupffer cells (KCs) in fatty liver is not clear at all. This study evaluates whether ER-stress of KCs is activated in fatty liver and accelerate IRI of fatty livers. ER-stress of KCs was activated in fatty liver, especially the IRE1α signal pathway. KCs with activated ER-stress secreted more proinflammatory cytokine to induce its M1-phenotypic shift in fatty liver, resulting in more severe IRI. Also, activated ER-stress of BMDMs in vitro by tunicamycin can induce its pro-inflammatory shift and can be reduced by 4-PBA, an ER-stress inhibitor. Knockdown of IRE1α could regulate the STAT1 and STAT6 pathway of macrophage to inhibit the M1-type polarization and promote M2-phenotypic shift. Furthermore, transfusion of IRE1α-knockdown KCs significantly reduced the liver IRI as well as the ROS of HFD feeding mice. Altogether, these data demonstrated that IRE1α of KCs may be a potential target to reduce the fatty liver associated IRI in liver transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine the dynamic and potentially synergistic influence of warm ischemia time (WIT) and excisional volume loss (EVL) on predicted rates of postpartial acute kidney injury (AKI) across a range of tumor complexities, and to investigate whether these modifiable variables sensitize the kidney to each other's damaging influence., Materials and Methods: We retrospectively reviewed 1245 patients between 2006 and 2016 with bilateral kidneys and enhancing renal masses in our single-institution robotic partial nephrectomy (PN) database. EVL was calculated as the difference between specimen and tumor volume based on pathologic measurements. Multivariate logistic regressions, followed by marginal effects, were run to examine the interaction of ischemia type, EVL, and radius, exophytic/endophytic properties, nearness of deepest tumor portion to collecting system or sinus, anterior/posterior and location relative to polar line score on rates of AKI., Results: We found a significant interaction effect of WIT and log EVL on predicted AKI (P < .001). Each doubling of EVL caused a 4.03% and 8.46% increased probability of AKI for WIT of <25 and >25 minutes, respectively. At an EVL of >5.5 cm 3 , prolonged WIT had statistically greater odds of causing AKI. These predicted effects on AKI were amplified for increasing radius, exophytic/endophytic properties, nearness of deepest tumor portion to collecting system or sinus, anterior/posterior and location relative to polar line scores (P < .001)., Conclusion: Although the adverse functional effects of WIT and parenchymal volume loss during PN have previously been described in isolation, our findings suggest that their influence on AKI is synergistic, especially in complex tumors. As such, additional attention should be given to limiting warm ischemia and maximizing surgical precision to avoid a "double hit" on postoperative renal function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Acute ischemic injury in the operated kidney after partial nephrectomy (PN) is often masked by a functional contralateral kidney; however, there is no practical method to assess this and its prognostic significance has not been defined., Objective: We propose a spectrum score to reflect the degree of ischemic insult in the ipsilateral kidney and study its relationship to subsequent functional recovery., Design, Setting, and Participants: From 2007 to 2014, 243 patients with a functional contralateral kidney underwent PN with necessary studies for detailed analysis of function and parenchymal mass before and after surgery in the ipsilateral kidney. Based on split function and percent parenchymal mass preserved in the ipsilateral kidney, we determined: serum creatinine (SCr) ideal-peak : expected peak SCr presuming no ischemic injury; and SCr worstcase-peak : expected peak SCr presuming temporary complete nonfunction of the ipsilateral kidney. The acute ipsilateral renal dysfunction spectrum score was defined: (observed peak SCr - SCr ideal-peak )/(SCr worstcase-peak - SCr ideal-peak ). Subsequent functional recovery was defined: (percent function preserved)/(percent mass saved)., Intervention: PN., Outcome Measurements and Statistical Analysis: Factors associated with spectrum score and relationship between spectrum score and subsequent functional recovery were evaluated by linear regression., Results and Limitations: Median duration of warm ischemia (n=152) was 21min (interquartile range [IQR] = 15-27) and hypothermia (n=91) 26min (IQR=23-30). Median parenchymal mass preservation was 83% (IQR=74-91%). Warm ischemia and longer ischemia duration associated with higher spectrum score (both p<0.05). Increased spectrum score (<25%, 25-50%, 50-75%, and >75% quartiles) had decreased functional recovery (98%, 94%, 90%, and 89%, respectively, p<0.001). However, this trend was not observed in the hypothermia cohort. On multivariable analysis spectrum score and ischemia type significantly associated with functional recovery (both p<0.01), while age and comorbidities failed to associate (p=0.3-0.7)., Conclusions: Acute ipsilateral renal dysfunction spectrum score unmasks the degree of ischemic insult in the operated kidney after PN and associates with functional recovery. While increased spectrum score associates with suboptimal recovery, even patients with a high spectrum score reached 89-90% recovery., Patient Summary: Acute functional decline after partial nephrectomy is difficult to evaluate in patients with two kidneys, but a proposed spectrum score can be used to evaluate this. Increased spectrum score reflects increased ischemia and may impact the functional recovery of the kidney., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Acute increase of serum creatinine (SCr) after partial nephrectomy (PN) is primarily due to parenchymal mass reduction or ischemia; however, only ischemia can impact subsequent functional recovery., Objective: We evaluate etiologies of acute kidney injury (AKI) after PN and their prognostic significance., Design, Setting, and Participants: From 2007-2014, 83 solitary kidneys managed with PN had necessary studies for detailed analysis of function and parenchymal mass before/after surgery. AKI was classified by Risk/Injury/Failure/Loss/Endstage classification and defined by either standard criteria (comparison to preoperative SCr) or proposed criteria (comparison to projected postoperative SCr based on parenchymal mass reduction). Subsequent recovery was defined as percent function preserved/percent mass saved., Intervention: PN., Outcome Measurements and Statistical Analysis: Predictive factors for AKI were evaluated by logistic regression. Relationship between AKI grade and subsequent functional recovery was assessed by linear regression., Results and Limitations: Median duration warm ischemia (n=39) was 20 min and hypothermia (n=44) was 29 min. Median parenchymal mass reduction was 11%. AKI occurred in 45 patients based on standard criteria and 38 based on proposed criteria, and reflected injury/failure (grade = 2/3) in 23 and 16 patients, respectively. On multivariable analysis, only ischemia time associated with AKI occurrence (p=0.016). Based on the proposed criteria, median recovery from ischemia was 99% in patients without AKI and 95%/90%/88% for patients with grades 1/2/3 AKI, respectively. The coefficient for association between AKI grade based on proposed criteria and subsequent functional recovery was -4.168 (p=0.018). Main limitation is limited patient cohort., Conclusions: Parenchymal mass reduction and ischemia both contribute to acute changes in SCr after PN. Classification of AKI by proposed criteria significantly associates with subsequent functional recovery. However, more robust numbers will be needed to further assess the merits of the proposed criteria. While AKI is associated with suboptimal recovery, even patients with grade 2/3 AKI reached 88-90% of recovery expected., Patient Summary: Acute decline in function after partial nephrectomy associates with more prolonged ischemia time, and appears to impact subsequent functional recovery. However, most kidneys eventually recover strongly, even if their function is sluggish in the first few days after surgery., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Ischemia is a potential contributor to decline of function after partial nephrectomy (PN), although loss of parenchymal mass related to excision and reconstruction appears to be a more significant factor. However, loss of parenchymal mass could also be due to global effects of ischemia leading to parenchymal atrophy. In this study, we evaluated parenchymal volumes in regions away from the operated site to assess for atrophy., Materials and Methods: A total of 164 patients undergoing PN for whom detailed analysis of function and parenchymal mass within the operated kidney could be performed were assessed for opposite pole volume (OPV) before and 4-12 months after surgery. Tumor location was required to be ≥2 cm away from the opposite polar line to exclude local effects related to excision or reconstruction. OPV was estimated by software analysis, and the ratio of the estimates (OPV ratio = postoperative OPV to preoperative OPV) was used to assess for atrophy., Results: Patient demographics and tumor characteristics were representative of conventional PN populations, and warm ischemia (n = 101; median, 21 minutes) and cold ischemia (n = 63; median, 26 minutes) were applied by surgeon discretion. OPVs before and after PN were 63.2 and 62.5 cm(3), respectively (P = .76). The median OPV ratio was 0.99 suggesting that significant atrophy did not occur. OPV ratio was 0.99 for warm ischemia cases and 0.99 for cold ischemia cases (P = .95)., Conclusion: Limited warm ischemia or hypothermia was not associated with significant parenchymal atrophy after PN, which suggests that parenchymal volume loss in this setting is primarily due to excision or reconstruction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To compare between the effects of cold and warm ischemia on the risk of deterioration of renal insufficiency in patients with T1 renal tumor managed by partial nephrectomy., Methods: This prospective randomized study was performed on 120 patients with chronic kidney disease, all having T1 renal tumors. Renal function was estimated by estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula. Patients were randomly divided into 2 groups: in group A, warm ischemia was used, and in group B, cold ischemia was used. All patients were treated by open partial nephrectomy. Patients were followed up for 2 years. The primary outcome of the study was eGFR at 2 years. Secondary outcomes were tumor recurrence, loss of follow-up, or patient death., Results: Mean age of patients was 60.7 ± 5.3 years. Associated chronic disease (diabetes and/or hypertension) was present in 93 patients. Worsening of renal insufficiency occurred within 1 month of surgery in 38 patients (27 in group A and 11 in group B). At 3 months follow-up, 21 of these 38 patients returned to their baseline eGFR. Warm ischemia rendered patients more prone to a decrease in eGFR after partial nephrectomy, with relative risk of 1.34 and 2 times at 3 months and 2 years of follow-up, respectively., Conclusion: Warm ischemia increases the risk of deterioration of renal functions in patients with renal insufficiency undergoing open partial nephrectomy for renal tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess renal functional deterioration after partial nephrectomy with warm and cold ischemia using (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scintigraphy parameters., Methods: Open partial nephrectomy was performed in 59 patients with warm ischemia and 64 patients with cold ischemia. (99m)Tc-MAG3 renal scintigraphy was performed and effective renal plasma flow was calculated to evaluate split renal function. In addition, regional (99m)Tc-MAG3 uptake was analyzed in the surgically unaffected parts to evaluate ischemic damage., Results: The mean tumor size in the warm and cold ischemia groups was 2.9 and 3.2 cm, respectively, and the mean ischemic time was 24.2 minutes (range, 8-46 minutes) and 26.7 min (range, 8-58 minutes), respectively. One week after surgery, effective renal plasma flow in the operated kidney decreased to 66.2% (from 160.2 to 105.4 mL/min/1.73 m(2)) in the warm ischemia group and to 77.4% (from 152.3 to 116.6 mL/min/1.73 m(2)) in the cold ischemia group. Regional (99m)Tc-MAG3 uptake changed to 89.2% of baseline in the warm ischemia group and 101.5% of baseline in the cold ischemia group. When the ischemic time was ≥ 25 minutes, regional (99m)Tc-MAG3 uptake in the warm ischemia group did not recover to the baseline level at 6 months. Multiple regression analyses demonstrated a significant correlation between ischemic time and the decrease in regional (99m)Tc-MAG3 uptake in the warm ischemia group, but not in the cold ischemia group., Conclusion: Warm ischemia for ≥ 25 minutes caused long lasting diffuse damage throughout the operated kidney, whereas cold ischemia for up to 58 minutes prevented ischemic injury to the renal remnant., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To analyze factors impacting postoperative renal function after open partial nephrectomy using both the clampless and clamped warm-ischemic technique., Methods: We studied a cohort of patients who underwent clamped partial nephrectomy (n = 164) and clampless partial nephrectomy (n = 64) from March 2002 to March 2009 with ≥ 12-months follow-up. Clamped partial nephrectomy used hilar occlusion before resection. Clampless partial nephrectomy used focal radio frequency coagulation to facilitate hemostasis before resection, nonischemic dissection/resection with hydro-dissection, or sharp resection after local compression. Demographics, tumor characteristics/RENAL nephrometry scores, perioperative variables, and complications were compared between the two methods. Multivariable analysis was performed to identify factors predicting de novo estimated glomerular filtration rate <60., Results: Patient characteristics were similar between groups. Mean RENAL score was greater in clamped (6.9) vs clampless (6.4, P = .026); complications (P = .430) and urine leaks (clampless partial nephrectomy 3.1% vs clamped-PN 7.3%, P = .360) were similar. Mean warm ischemia time (min) was 24.5 for clamped partial nephrectomy. De novo estimated glomerular filtration rate <60(%) at last follow up was 13.5 (clamped) vs 3.1 (clampless) (P = .071). Multivariable analysis of the entire cohort revealed increasing body mass index (OR 1.1, P = .042) and RENAL score (OR 1.71, P = .002) as being independently associated with development of postoperative de novo estimated glomerular filtration rate <60. Multivariable analysis of the clamped subgroup demonstrated increasing body mass index (OR 1.12, P = .028), RENAL score (OR 1.56, P = .010), and ischemia time (OR 1.15, P = .042) as independent factors associated with de novo estimated glomerular filtration rate <60., Conclusion: Body mass index and RENAL score were factors predictive of development of de novo estimated glomerular filtration rate <60 after partial nephrectomy, with increasing warm ischemia time also being predictive in clamped partial nephrectomy patients. Further investigation and long-term functional data are requisite., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Renal scintigraphy may allow long-term monitoring of ischemic damage after partial nephrectomy (PN)., Objective: Evaluate use of renal scintigraphy for evaluating long-term effects of warm ischemia on renal function in patients with a normal contralateral kidney., Design, Setting, and Participants: We prospectively examined kidney function of 54 patients who underwent laparoscopic PN (LPN). Minimum follow-up time was 4 yr., Intervention: LPN was performed with warm ischemia by transperitoneal or retroperitoneal approach., Measurements: Demographic, perioperative, and pathologic data and postoperative complications were registered. Split renal function (SRF) and effective renal plasma flow (ERPF) were evaluated by renal scintigraphy preoperatively, at 3 and 12 mo postoperatively, then yearly. Baseline weighted differentials (b-WDs) of both SRF and ERPF in the affected kidney were calculated between baseline condition and every time point. Multivariate linear regression was used to find independent variables for increased b-WDs at 3 and 48 mo. P values<0.05 were considered significant., Results and Limitations: The SRF and ERPF of kidneys treated by LPN decreased significantly at month 3 and subsequently remained stable through the duration of follow-up. Conversely, neither serum creatinine nor estimated glomerular filtration rate changed significantly during follow-up. The regression model showed statistical significance at month 3 for warm ischemia time (WIT) and age, whereas at 48 mo, statistical significance was reached by WIT alone. No new onset of cardiovascular disease was registered. No evidence of local recurrence was recorded with computed tomography scan. Our study may be underpowered due to small sample size; however, this is one of the largest long-term prospective series using renal scintigraphy to evaluate the renal function after LPN., Conclusions: WIT contributes to irreversible kidney damage observed at month 3 that does not appear to worsen., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Warm ischemia time (WIT) and complication rates are two important parameters for evaluating the perioperative results of robot-assisted partial nephrectomy (RAPN). Few data are available about the clinical predictors of WIT and overall complications., Objective: To identify clinical predictors of WIT and perioperative complications., Design, Setting, and Participants: This is a retrospective study including 347 patients who underwent RAPN for suspicious renal cell carcinoma (RCC) at four referral centers from September 2008 to September 2010., Intervention: All patients underwent RAPN using the da Vinci S Surgical System with hilar clamping., Measurements: WIT >20 min and overall complication rates were the main outcomes. Postoperative complications were classified according to the Clavien/Dindo system. Moreover, the following perioperative variables were considered: clinical tumor size, anatomical tumor characteristics according to Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score, surgeon experience, console time, blood loss, and upper collecting system (UCS) repair., Results and Limitations: WIT >20 min was reported in 125 (36%) cases. Intraoperative and postoperative complications were observed in 10 (2.9%) and 41 (11.8%) cases, respectively. Surgeon experience (odds ratio [OR]: 6.381; 95% confidence interval [CI], 3.687-11.042; p<0.001), clinical tumor size (OR: 1.022; 95% CI, 1.002-1.044; p=0.03), the other anatomic characteristics determined by the PADUA classification score (OR: 1.294; 95% CI, 1.080-1.549; p=0.005), and the UCS repair (OR: 2.987; 95% CI, 1.728-5.165; p<0.001) turned out to be independent predictors of WIT >20 min. Similarly, surgeon experience (OR: 3.937; 95% CI, 2.011-7.705; p<0.001), clinical tumor size (OR: 1.033; 95% CI, 1.009-1.058; p=0.007), and the other anatomical characteristics determined by the PADUA classification score (OR: 1.427; 95% CI, 1.149-1.773; p<0.001) turned out to be independent predictors of overall complication rates. The retrospective design is the main limitation of this multicenter, international study. Therefore, some patient characteristics and comorbidities were not recorded., Conclusions: Anatomic tumor characteristics as determined by the PADUA classification score were independent predictors of WIT and overall complications, once adjusted for the effects of surgeon experience and clinical tumor size., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effects of warm ischemia time (WIT) and quantity and quality of kidney preserved on renal functional recovery after partial nephrectomy (PN). The effect of WIT relative to these other parameters has recently been challenged., Methods: We identified 362 consecutive patients with a solitary kidney who had undergone PN using warm ischemia. Multivariate models with multiple imputations were used to evaluate the associations with acute renal failure and new-onset stage IV chronic kidney disease (CKD)., Results: The median WIT was 21 minutes (range 4-55), the median percentage of kidney preserved was 80% (range 25%-98%), and the median preoperative glomerular filtration rate (GFR) was 61 mL/min/1.73 m2 (range 11-133). Postoperative acute renal failure occurred in 70 patients (19%). Of the 226 patients with a preoperative GFR>30 mL/min/1.73 m2, 38 (17%) developed new-onset stage IV CKD during follow-up. On multivariate analysis, the WIT (P=.021), percentage of kidney preserved (P=.009), and preoperative GFR (P<.001) were significantly associated with acute renal failure, and only the percentage of kidney preserved (P<.001) and preoperative GFR (P<.001) were significantly associated with new-onset stage IV CKD during follow-up. Using our previously published cutpoint of 25 minutes, a WIT of >25 minutes remained significantly associated with new-onset stage IV CKD in a multivariate analysis adjusting for the quantity and quality factors (hazard ratio 2.27, P=.049)., Conclusion: Our results have validated that the quality and quantity of kidney are the most important determinants of renal function after PN. In addition, we have also demonstrated that the WIT remains an important modifiable feature associated with short- and long-term renal function. The precision of surgery, maximizing the amount of preserved, vascularized parenchyma, should be a focus of study for optimizing the PN procedure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Few studies assessing the functional change of each kidney following warm ischaemia after partial nephrectomy are available., Objectives: Our aim was to identify the effects of the warm ischaemic time (WIT) on renal function after partial nephrectomy under the pneumoperitoneum., Design, Setting, and Participants: Forty-four consecutive patients who underwent laparoscopic partial nephrectomy (LPN) or robot-assisted partial nephrectomy (RAPN) from June 2008 to May 2009 for a single cT1 renal tumour were included in this prospective protocol., Measurements: Technetium Tc 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scintigraphy was used to determine the glomerular filtration rate (GFR) of both kidneys and each kidney individually. Tc 99m-DTPA GFR was performed preoperatively and 3 mo postoperatively. In addition, we analysed Tc 99m-DTPA scintigraphy GFR regionally in the healthy areas of the affected kidney., Results and Limitations: Patients with WIT > 28 min had a significantly greater decrease in the GFR of the affected kidney (p = 0.031). The GFR of the affected kidney showed a significant decrease perioperatively (46.4 ± 14.3 to 37.9 ± 11.9 ml/min per 1.73 m²; p = 0.003). The functional change of the nonaffected kidney showed an increasing trend (47.5 ± 13.8 to 51.4 ± 14.3 ml/min per 1.73 m²), although it was not statistically significant (p=0.103). Regional Tc 99m-DTPA GFR of both affected kidney and nonaffected kidney showed no significant differences perioperatively (6.3 ± 1.8 to 6.1 ± 1.9 ml/min per 1.73 m²; p = 0.641; 6.6 ± 1.9 to 7.1 ± 2.0 ml/min per 1.73 m² ; p = 0.200). On multivariate analysis, preoperative GFR, resected volume of marginal healthy tissue, and WIT were independent predictors for functional reduction of the affected kidney (p < 0.05). The study was limited by small numbers and short follow-up periods., Conclusions: Stationary overall renal function after LPN or RAPN is masked possibly by functional compensation of the contralateral healthy kidney. The damage of the affected kidney estimated by scintigraphy occurs when WIT exceeds 28 min during partial nephrectomy under the pneumoperitoneum., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of Postcond on renal ischemia-reperfusion (I/R) injury in a canine model. I/R injury is the most common cause of renal dysfunction. Ischemic postconditioning (Postcond) is a phenomenon by which intermittent interruptions of blood flow in the early phase of reperfusion can protect organs from I/R injury., Material and Methods: Forty adult male mongrel dogs were randomly divided into five groups of eight dogs each. Animals underwent 60 minutes of renal pedicle occlusion followed by reperfusion for 72 hours. Postcond was performed by 15-second, 30-second, or 1-minute I/R for six or three cycles. Blood and urine were collected at different reperfusion time points (24, 48, and 72 hours), and blood urea nitrogen (BUN), creatinine (Cr) levels, urine N-acetyl-β-D-glucosaminidase (NAG), and Cr levels were assayed. Kidney samples were harvested after I/R, and renal superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) concentrations were measured, respectively. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) assay in the tissue samples., Results: Compared with the sham group, I/R resulted in renal dysfunction, decreased SOD levels, increased MDA and MPO levels, and increased apoptosis indexes. However, Postcond attenuated the aforementioned effects, the protection of which in the Postcond of 15-second reperfusion/ischemia for six cycles was the most notable., Conclusions: Postcond exerts protective effects on renal (I/R) injury. It may be a promising strategy against I/R injury in clinical practice. Its mechanisms may involve reduction of lipid peroxidation and cellular apoptosis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The safe duration of warm ischemia during partial nephrectomy (PN) remains controversial., Objective: To compare the short- and long-term renal effects of warm ischemia versus no ischemia in patients with a solitary kidney., Design, Setting, and Participants: Using the Cleveland Clinic and Mayo Clinic databases, we identified 458 patients who underwent open (n=411) or laparoscopic (n=47) PN for a renal mass in a solitary kidney between 1990 and 2008. Patients treated with cold ischemia were excluded., Measurements: Associations of ischemia type (none vs warm) with short- and long-term renal function were evaluated using logistic or Cox regression models., Results and Limitations: No ischemia was used in 96 patients (21%), while 362 patients (79%) had a median of 21 min (range: 4-55) of warm ischemia. Patients treated with warm ischemia had a significantly higher preoperative glomerular filtration rate (GFR; median: 6 ml/min per 1.73 m(2) vs 54 ml/min per 1.73 m(2); p<0.001) and larger tumors (median: 3.4 cm vs 2.5 cm; p<0.001) compared with patients treated with no ischemia. Warm ischemia patients were significantly more likely to develop acute renal failure (odds ratio [OR]: 2.1; p=0.044) and a GFR <15 ml/min per 1.73 m(2) in the postoperative period (OR: 4.2; p=0.007) compared with patients who did not have hilar clamping. Among the 297 patients with a preoperative GFR >or=30 ml/min per 1.73 m(2), patients with warm ischemia were significantly more likely to develop new-onset stage IV chronic kidney disease (hazard ratio: 2.3; p=0.028) during a mean follow-up of 3.3 yr. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of PN in a multivariable analysis. Limitations include surgeon selection bias when determining type of ischemia., Conclusions: Warm ischemia during PN is associated with adverse renal consequences. Although selection bias is present, PN without ischemia should be used when technically feasible in patients with a solitary kidney., ((c) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The safe duration of warm ischemia during partial nephrectomy remains controversial., Objective: Our aim was to evaluate the short- and long-term renal effects of warm ischemia in patients with a solitary kidney., Design, Setting, and Participants: Using the Cleveland Clinic and Mayo Clinic databases, we identified 362 patients with a solitary kidney who underwent open (n=319) or laparoscopic (n=43) partial nephrectomy using warm ischemia with hilar clamping., Measurements: Associations of warm ischemia time with renal function were evaluated using logistic or Cox regression models first as a continuous variable and then in 5-min increments., Results and Limitations: Median tumor size was 3.4 cm (range: 0.7-18.0 cm), and median ischemia time was 21 min (range: 4-55 min). Postoperative acute renal failure (ARF) occurred in 70 patients (19%) including 58 (16%) who had a glomerular filtration rate (GFR) <15 ml/min per 1.73 m(2) within 30 d of surgery. Among the 226 patients with a preoperative GFR >or=30 ml/min per 1.73 m(2) and followed >or=30 d, 38 (17%) developed new-onset stage IV chronic kidney disease during follow-up. As a continuous variable, longer warm ischemia time was associated with ARF (odds ratio: 1.05 for each 1-min increase; p<0.001) and a GFR<15 (odds ratio: 1.06; p<0.001) in the postoperative period, and it was associated with new-onset stage IV chronic kidney disease (hazard ratio: 1.06; p<0.001) during follow-up. Similar results were obtained adjusting for preoperative GFR, tumor size, and type of partial nephrectomy in a multivariable analysis. Evaluating warm ischemia in 5-min increments, a cut point of 25 min provided the best distinction between patients with and without all three of the previously mentioned end points. Limitations include the retrospective nature of the study., Conclusions: Longer warm ischemia time is associated with short- and long-term renal consequences. These results suggest that every minute counts when the renal hilum is clamped., ((c) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Although nephron-sparing surgery (NSS) has been reported not to affect total renal function, the functional damage of the operated kidney is masked by the contralateral kidney in elective indications., Objective: To determine ischemic renal damage after NSS., Design, Setting, and Participants: From August 2005 to October 2007, 32 consecutive patients with elective indications underwent NSS. The mean tumor diameter was 2.6 cm., Intervention: Of our patients, the open surgery was performed in 20 patients, and laparoscopic surgery was performed in 12 patients. NSS was performed by hilar clamping with a warm ischemic time of 24.3 min., Measurements: We analyzed effective renal plasma flow (ERPF) calculated from (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG-3) renal scintigraphy and renal parenchymal volume (RPV) measured from computed tomography (CT) scan. In addition, we analyzed (99m)Tc-MAG-3 uptake regionally in the surgically non-affected parts. (99m)Tc-MAG-3 and CT scans were performed preoperatively and 1 wk and 6 mo postoperatively., Results and Limitations: One week after NSS, ERPF of the operated kidney decreased by 28.7% (from 158.9 to 113.3 ml/min per 1.73 m(2), p<0.001), and RPV decreased by 12.6% (from 149.8 to 131.0 cm(3), p<0.001). These changes were stable for 6 mo. Regional (99m)Tc-MAG-3 uptake of the operated kidney with an ischemic time of > or = 25 min decreased to 61.8% after 1 wk and 70.9% after 6 mo. In contrast, with ischemic times within 25 min, regional (99m)Tc-MAG-3 uptake was 87.4% after 1 wk and 94.4% after 6 mo. This is a relatively small study, and the follow-up period is short. A larger sample size and longer follow-up may be required., Conclusions: Although total renal function was almost unaffected before and after NSS, a warm ischemic time of > or = 25 min caused irreversible damage distributed diffusely throughout the operated kidney.