This is 2 presentations on lap partial nephrectomy during the 2014 CUA advanced Lap Course.
laparoscopic partial nephrectomy
renal clamping
zero ischemia partial nephrectomy
margin status in partial nephrectomy
Standard partial nephrectomy vs eneucleation.
Superselective microdissection
This is 2 presentations on lap partial nephrectomy during the 2014 CUA advanced Lap Course.
laparoscopic partial nephrectomy
renal clamping
zero ischemia partial nephrectomy
margin status in partial nephrectomy
Standard partial nephrectomy vs eneucleation.
Superselective microdissection
This is 2 presentations on lap partial nephrectomy during the 2014 CUA advanced Lap Course.
laparoscopic partial nephrectomy
renal clamping
zero ischemia partial nephrectomy
margin status in partial nephrectomy
Standard partial nephrectomy vs eneucleation.
Superselective microdissection
ADVANCED LAPAROSCOPIC AND ROBOTIC UROLOGY SKILLS FORUM
BULLDOGS VS ENBLOC CLAMPING AND MINIMIZING WARM
ISCHEMIA Christopher French MD FRCSC Genitourinary Oncology/ EndoUrology Eastern Heath, Memorial University of Newfoundland June 2014 HILAR MANAGEMENT: CLAMP TIME!!! CLAMPLESS EVIDENCE TECHNIQUES RISKS Points of Discussion Contents Introduction 49 Indications and Contraindications 49 Surgical Technique 50 Comparison of Open and Laparoscopic Partial Nephrectomy 53 Complications of Laparoscopic Partial Nephrectomy 53 Current Issues and Future Directions 54 Renal Hilar Clamping 54 Laparoscopic Renal Hypothermia 55 Hemostatic Aids 55 Conclusions 56 References 56 Introduction With widespread use of modern imaging techniques, renal tumors are commonly diagnosed incidentally. These tumors are often small with favorable biological behavior, including a slow growth rate and a low inci- dence of local recurrence and metastasis. Moreover, small incidentally detected renal tumors have a 22% 40% chance of being benign on final pathological analysis [1]. With strong evidence supporting ne- phron-sparing surgery (NSS) for renal tumors less than 4 cm and the evolution of minimally invasive surgical technique, there has been a trend away from radical nephrectomy in the management of small renal tumors. In the past decade, several minimally invasive ther- apy options for NSS have been developed in an at- tempt to minimize operative morbidity while achiev- ing comparable oncological outcomes and preserving renal function. These minimally invasive procedures comprise tumor excision (laparoscopic partial ne- phrectomy), which aims to duplicate the established technique of open partial nephrectomy and probe-ab- lative strategies (cryotherapy and radiofrequency abla- tion). In this chapter, we discuss the current status of laparoscopic partial nephrectomy. Compared to radical nephrectomy, laparoscopic partial nephrectomy is a considerably more techni- cally challenging procedure. Issues of renal hypother- mia, renal parenchymal hemostasis, pelvicaliceal re- construction, and parenchymal renorrhaphy by pure laparoscopic techniques pose unique challenges to the surgeon. Nonetheless, ongoing advances in laparo- scopic techniques and operator skills have allowed the development of a reliable technique of laparoscopic partial nephrectomy, which aims to replicate the es- tablished procedure of open partial nephrectomy [2]. As such, laparoscopic partial nephrectomy is emerging as an attractive minimally invasive nephron-sparing option at select institutions. The worldwide experience with laparoscopic partial nephrectomy is summarized in Table 1 [39]. Indications and Contraindications Initially, laparoscopic partial nephrectomy was re- served for the select patient with a favorably located, small, peripheral, superficial, and exophytic tumor [1012]. With experience, we have carefully expanded the indications to select patients with more complex tumors: tumor invading deeply into the parenchyma up to the collecting system or renal sinus [13], upper pole tumors requiring concomitant adrenalectomy [14], completely intrarenal tumor, tumor abutting the renal hilum, tumor in a solitary kidney, or a tumor substantial enough to require heminephrectomy [15]. Although there is growing evidence supporting elec- tive partial nephrectomy for select tumors 47 cm in size [16], laparoscopic partial nephrectomy for these complex tumors is most often utilized in the setting of compromised or threatened global nephron mass wherein nephron preservation is an important con- 3.1 Laparoscopic Partial Nephrectomy Antonio Finelli, Inderbir S. Gill a 3.1 Laparoscopic Partial Nephrectomy 51 Fig. 1. Retroperitoneal laparoscopic partial nephrectomy. Because of the limited working space, the renal vein and artery were initially iso- lated and controlled with laparoscopic bull- dog clamps. A Satinsky clamp is now routinely used. Adapted from [2] Fig. 2. Transperitoneal laparoscopic partial nephrectomy. A laparo- scopic Satinsky clamp is used to clamp the hilum en bloc. Adapted from [2] a 3.1 Laparoscopic Partial Nephrectomy 51 Fig. 1. Retroperitoneal laparoscopic partial nephrectomy. Because of the limited working space, the renal vein and artery were initially iso- lated and controlled with laparoscopic bull- dog clamps. A Satinsky clamp is now routinely used. Adapted from [2] Fig. 2. Transperitoneal laparoscopic partial nephrectomy. A laparo- scopic Satinsky clamp is used to clamp the hilum en bloc. Adapted from [2] CLAMP TIME Less than 30 minutes !!!!! But there is no safe time Setup, parenchymal and deep sutures ready and prepared Early unclamping Artery only vs Hilum Tumors >4cm, central location and BMI >30 assoc with longer clamp times Vessels dissected and ready, clamped only if needed ? Partial arterial clamping Kidney Cancer Is Renal Warm Ischemia over 30 Minutes during Laparoscopic Partial Nephrectomy Possible? One-Year Results of a Prospective Study Francesco Porpiglia a, *, Julien Renard a , Michele Billia a , Francesca Musso a , Alessandro Volpe a , Rodolfo Burruni a , Carlo Terrone a , Loredana Colla b , Giorgina Piccoli b , Valerio Podio c , Roberto Mario Scarpa a a Department of Urology, University of Turin, San Luigi Hospital, Orbassano Torino, Italy b Department of Nephrology, University of Turin, San Giovanni Battista Hospital, Torino, Italy c Department of Radiology and Nuclear Medicin, University of Turin, San Luigi Hospital, Orbassano, Torino, Italy e ur op e an ur ol og y 5 2 ( 2 0 0 7 ) 1 1 7 0 1 1 7 8 avai l abl e at www. sci encedi r ect . com j our nal homepage: www. eur opeanur ol ogy. com Article info Article history: Accepted April 5, 2007 Published online ahead of print on April 11, 2007 Keywords: Laparoscopy Partial nephrectomy Renal function Warm ischemia Abstract Objective: To evaluate renal damage and impairment of renal function 1 yr after laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. Methods: From July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30 min. Kidney damage markers (daily protei- nuria and tubular enzymes) and renal function (serum creatinine, cysta- tin C, and creatinine clearances) were assessed on postoperative days 1 and 5 and at 12 mo. Glomerular ltration rate (GFR) was evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was performed using the Student t test and logistic regression analysis. Results: In terms of kidney damage and renal function markers, the statistical analysis demonstrated that at 1 yr there was complete return to the normal range and no statistical difference between the values at the various time points. The GFR was not signicantly different before and 3 mo after surgery. In terms of scintigraphy of the operated kidney, the values were 48.35 3.82%(4050%) before the procedure, 36.88 8.42 (1650%) on postoperative day 5 ( p = 0.0001), 40.56 8.96 (2050%) at 3 mo ( p = 0.003), and 42.8 7.2% (2050%) 1 yr after surgery ( p = 0.001). Conclusion: Our results demonstrate that kidney damage occurs during LPN when warm ischemia is >30 min. This damage is only partially reversible and efforts should be made to keep warm ischemia within 30 min. #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Torino, Italy. Tel. +39 011 9026558; Fax: +39 011 9026244. E-mail address: porpiglia@libero.it (F. Porpiglia). 0302-2838/$ see back matter #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2007.04.024 Kidney Cancer Is Renal Warm Ischemia over 30 Minutes during Laparoscopic Partial Nephrectomy Possible? One-Year Results of a Prospective Study Francesco Porpiglia a, *, Julien Renard a , Michele Billia a , Francesca Musso a , Alessandro Volpe a , Rodolfo Burruni a , Carlo Terrone a , Loredana Colla b , Giorgina Piccoli b , Valerio Podio c , Roberto Mario Scarpa a a Department of Urology, University of Turin, San Luigi Hospital, Orbassano Torino, Italy b Department of Nephrology, University of Turin, San Giovanni Battista Hospital, Torino, Italy c Department of Radiology and Nuclear Medicin, University of Turin, San Luigi Hospital, Orbassano, Torino, Italy e ur op e an ur ol og y 5 2 ( 2 0 0 7 ) 1 1 7 0 1 1 7 8 avai l abl e at www. sci encedi r ect . com j our nal homepage: www. eur opeanur ol ogy. com Article info Article history: Accepted April 5, 2007 Published online ahead of print on April 11, 2007 Keywords: Laparoscopy Partial nephrectomy Renal function Warm ischemia Abstract Objective: To evaluate renal damage and impairment of renal function 1 yr after laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. Methods: From July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30 min. Kidney damage markers (daily protei- nuria and tubular enzymes) and renal function (serum creatinine, cysta- tin C, and creatinine clearances) were assessed on postoperative days 1 and 5 and at 12 mo. Glomerular ltration rate (GFR) was evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was performed using the Student t test and logistic regression analysis. Results: In terms of kidney damage and renal function markers, the statistical analysis demonstrated that at 1 yr there was complete return to the normal range and no statistical difference between the values at the various time points. The GFR was not signicantly different before and 3 mo after surgery. In terms of scintigraphy of the operated kidney, the values were 48.35 3.82%(4050%) before the procedure, 36.88 8.42 (1650%) on postoperative day 5 ( p = 0.0001), 40.56 8.96 (2050%) at 3 mo ( p = 0.003), and 42.8 7.2% (2050%) 1 yr after surgery ( p = 0.001). Conclusion: Our results demonstrate that kidney damage occurs during LPN when warm ischemia is >30 min. This damage is only partially reversible and efforts should be made to keep warm ischemia within 30 min. #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Torino, Italy. Tel. +39 011 9026558; Fax: +39 011 9026244. E-mail address: porpiglia@libero.it (F. Porpiglia). 0302-2838/$ see back matter #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2007.04.024 Kidney Cancer Is Renal Warm Ischemia over 30 Minutes during Laparoscopic Partial Nephrectomy Possible? One-Year Results of a Prospective Study Francesco Porpiglia a, *, Julien Renard a , Michele Billia a , Francesca Musso a , Alessandro Volpe a , Rodolfo Burruni a , Carlo Terrone a , Loredana Colla b , Giorgina Piccoli b , Valerio Podio c , Roberto Mario Scarpa a a Department of Urology, University of Turin, San Luigi Hospital, Orbassano Torino, Italy b Department of Nephrology, University of Turin, San Giovanni Battista Hospital, Torino, Italy c Department of Radiology and Nuclear Medicin, University of Turin, San Luigi Hospital, Orbassano, Torino, Italy e ur op e an ur ol og y 5 2 ( 2 0 0 7 ) 1 1 7 0 1 1 7 8 avai l abl e at www. sci encedi r ect . com j our nal homepage: www. eur opeanur ol ogy. com Article info Article history: Accepted April 5, 2007 Published online ahead of print on April 11, 2007 Keywords: Laparoscopy Partial nephrectomy Renal function Warm ischemia Abstract Objective: To evaluate renal damage and impairment of renal function 1 yr after laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. Methods: From July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30 min. Kidney damage markers (daily protei- nuria and tubular enzymes) and renal function (serum creatinine, cysta- tin C, and creatinine clearances) were assessed on postoperative days 1 and 5 and at 12 mo. Glomerular ltration rate (GFR) was evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was performed using the Student t test and logistic regression analysis. Results: In terms of kidney damage and renal function markers, the statistical analysis demonstrated that at 1 yr there was complete return to the normal range and no statistical difference between the values at the various time points. The GFR was not signicantly different before and 3 mo after surgery. In terms of scintigraphy of the operated kidney, the values were 48.35 3.82%(4050%) before the procedure, 36.88 8.42 (1650%) on postoperative day 5 ( p = 0.0001), 40.56 8.96 (2050%) at 3 mo ( p = 0.003), and 42.8 7.2% (2050%) 1 yr after surgery ( p = 0.001). Conclusion: Our results demonstrate that kidney damage occurs during LPN when warm ischemia is >30 min. This damage is only partially reversible and efforts should be made to keep warm ischemia within 30 min. #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Torino, Italy. Tel. +39 011 9026558; Fax: +39 011 9026244. E-mail address: porpiglia@libero.it (F. Porpiglia). 0302-2838/$ see back matter #2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2007.04.024 WARM ISCHEMIA 18 patients Lap Partial with warm ischemia >30min serum creatinine, whereas creatinine clearance showed a paradoxical increase. The GFR (evaluated by nuclear medicine using 51 Cr-EDTA) was not significantly different before and 3 mo after the procedure: mean GFR was 91.60 22.68 ml/min/1.73 m 2 preoperatively and 79.12 13.69 ml/min/1.73 m 2 3 mo after surgery ( p = ns) (Table 5). As far as the contribution of the operated kidney to the overall renal function (evaluated by renal scintigraphy with 99m Tc-MAG3) is concerned, the preoperative value was 48.35 3.82% (range: 40 50%), 36.88 8.42%(range: 1650%) on postoperative day 5 ( p = 0.0001), 40.56 8.96% (range: 2050%) at 3 mo ( p = 0.003), and 42.8 7.2% (range: 2050%) 1 yr after surgery ( p = 0.001) (Table 5). One year after surgery, there is still a significant difference com- pared to the preoperative values, although it is evident that after an initial drop there is a trend toward a progressive recovery (Fig. 2). However, it is important to point out that the number of patients included in this study could affect the statistical power. At the 1-yr follow-up, no patient had developed new morbidities. As far as the logistic regression model is con- cerned, the statistical analysis demonstrated that the loss of function in the operated kidney (eval- uated by radionuclide scintigraphy) is not influ- enced by lesion size at pathology, patient age, and presence of comorbidities, but it is influenced significantly ( p < 0.05) by the maximum thickness of resected healthy parenchyma and duration of warm ischemia. The loss of renal function is maximal between 32 and 42 min of warm ischemia time, as shown by the drop of the curve in Fig. 3. Between 42 and 60 min, the curve flattens out, demonstrating a minor further loss of function when the warm ischemia time is in this range. 4. Discussion Althoughconsidereda challenging technique, LPNis gaining wide acceptance worldwide, especially in urologic departments where advanced laparoscopy is carried out [26]. To perform an accurate surgery, it is essential to resect the lesion and to obtain hemostasis in a short warm ischemia time to avoid kidney damage [3,27]. According to Rocca Rossetti [10], warm ischemia in open surgery can be classified as follows: (1) <10 minharmless; (2) up to 30 mingenerally reversible lesions; (3) >30 minrisk of irreversible parenchymal lesions increasing rapidly with the ischemic time; and(4) >60 minirreversible lesions. Regarding the site of kidney damage, the same author states that nephrons react differently to ischemia; glomeruli tolerate the ischemia better than tubular epithelia, whereas proximal convo- luted tubules are more sensitive to ischemic damage [10]. More recently, other authors suggested that warm ischemia determines a reduction in medul- lary blood flow causing hypoxic injury to the tubular structures in this region [9]. Furthermore, it seems that the degree of damage is proportional to the warm ischemia time. The higher sensitivity of the proximal tubuli to ischemia is due to a low capacity of the cells to generate adenosine triphosphate (ATP), whereas the remaining tubular cells are protected by the persistence of ATP. When warm ischemia is prolonged, the cells from the distal Fig. 2 Contribution of operated kidney to the overall renal function at the various time points (radionuclide renal scintigraphy with 99m Tc-mercaptoacetyltriglycine). POD = postoperative day. Fig. 3 Logistic regression model. Full orange curve = evolution of kidney damage over time; it is evident that between 32 and 42 min there is a major drop, corresponding to the phase in which parenchymal damage is maximum. The starting point of the critical phase of warm ischemia is at the 32-min time mark. The interrupted curves correspond to the confidence intervals. e ur op e an ur ol og y 5 2 ( 2 0 0 7 ) 1 1 7 0 1 1 7 8 1175 IS THERE A SAFE WARM ISCHEMIA TIME? Kidney Cancer Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney R. Houston Thompson a, *, Brian R. Lane b , Christine M. Lohse a , Bradley C. Leibovich a , Amr Fergany b , Igor Frank a , Inderbir S. Gill c , Steven C. Campbell b , Michael L. Blute a a Mayo Medical School and Mayo Clinic, Rochester, MN, USA b Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA c Keck School of Medicine, University of Southern California, Los Angeles, CA, USA E UR OP E AN UR OL OGY XXX ( 2 0 1 0 ) XXX XXX avai l abl e at www. sci encedi r ect . com j our nal homepage: www. eur opeanur ol ogy. com 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Article info Article history: Accepted May 31, 2010 Published online ahead of print on Keywords: Ischemia Kidney neoplasms Postoperative complications Nephrectomy Warm ischemia Abstract Background: The safe duration of warmischemia 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 identied 458 patients who underwent open (n = 411) or laparo- scopic (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: 455) of warm ischemia. Patients treated with warm ischemia had a signicantly higher preoperative glomerular ltration rate (GFR; median: 61 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 signicantly 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 30 ml/min per 1.73 m 2 , patients with warm ischemia were signicantlymorelikelytodevelopnew-onset stageIVchronickidneydisease(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 PNina multivariable analysis. Limitations include surgeon selection bias when determining type of ischemia. Conclusions: Warm ischemia during PN is associated with adverse renal conse- quences. Although selection bias is present, PN without ischemia should be used when technically feasible in patients with a solitary kidney. # 2010 Published by Elsevier B.V. on behalf of European Association of Urology. * Corresponding author. Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel. +507 284 3981; Fax: +507 284 4951. E-mail address: Thompson.robert@mayo.edu (R.H. Thompson). EURURO 3489 16 Please cite this article in press as: Thompson RH, et al. Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney. Eur Urol (2010), doi:10.1016/j.eururo.2010.05.048 0302-2838/$ see back matter #2010 Published by Elsevier B.V. on behalf of European Association of Urology. doi:10.1016/j.eururo.2010.05.048 1.73 m 2 and 30 d of GFR follow-up, 47 (16%) developed new-onset stage IV chronic kidney disease during follow-up. Within this subset, mean follow-up for patients treated without ischemia was 5.3 yr (median: 4.2; range: 0.218.2) and 2.7 yr (median: 1.6; range: 0.119.0) for patients treated withwarmischemia. MedianGFR(change frompreoperative GFR) at last follow-up for patients treated with no ischemia andwarmischemia was 54.3(0.9) and48.2(12.7) ml/min per 1.73 m 2 , respectively. Patients treated with warm ischemia were significantly more likely to develop new- onset stage IV chronic kidney disease (HR: 2.3; 95% CI, 1.1 4.9; p = 0.028) compared with patients treated with no ischemiaduringfollow-up(Fig. 1). Adjustingfor preoperative GFR, tumor size, and type of PN in a multivariable analysis, patients treated with warmischemia remained at significant risk of new-onset stage IV chronic kidney disease (HR: 2.6; 95% CI, 1.15.8; p = 0.022). When these analyses were repeated on the subset of patients treated with open PN only, warm ischemia remained significantly associated with these end points after multivariable adjustment for preoper- ative GFR and tumor size (Table 2, Fig. 2). 4. Discussion In this report, we update our previous collaboration evaluating renal functional outcomes in patients with a solitary kidney treated with PN. In these updated results, we include nearly twice as many patients (458 vs 259 treated with no ischemia or warmischemia), we better assess renal function with GFR (as opposed to serum creatinine alone), and we include patients treated with both open and laparoscopic approaches compared with our prior analysis [3]. Our data suggest that warm ischemia during PN is associated with an increased risk of ARF in the postopera- tive period and increased risk of new-onset stage IV chronic kidney disease during follow-up when compared with patients managed without hilar clamping. Although we did not observe an increased risk of dialysis (either temporary or permanent) for patients treated with warm ischemia, it should be noted that renal function decline in a graded fashion increases the risk of cardiovascular morbidity, hospitalization, and death from any cause [2]. For tumors amenable to enucleation, these observations support the use of no ischemia or regional compression during PN, especially in the setting of a solitary kidney. The renal cortex is exquisitely sensitive to warm ischemia, as metabolic activities are predominantly aerobic. Immediately following renal arterial occlusion, adenosine triphosphates begin to break down into monophosphate nucleotides, providing energy for structural and functional cellular integrity [11,12]. As energy sources become rapidly depleted in an anaerobic environment, cellular membrane transport mechanisms fail, and an influx of salt and water results in cellular edema and death [11]. Although the maximal safe duration of warm ischemia is controversial, our groups individually [7,8] and in collaboration [3] have observed that warm ischemia should be limited to 20 min whenever feasiblea notion that was recently supported by an international collaborative review of the literature [5]. However, the current analysis does not address the maximum time during which interruption of renal blood flow is best tolerated. Rather, we chose to focus on a group of patients for whom the surgeon decided that cold ischemia was not needed (ie, the tumor was sufficiently exophytic or small enough that the surgeon determined that the maximum duration of warm ischemia would be <2030 min). During the study time period, standard practice at both Mayo Clinic and Cleveland Clinic was to use hypothermic conditions for complex tumors where >2030 min of ischemia was anticipated. Thus, patients who received cold ischemia were excluded from this analysis. Although selection bias still exists among our cohort of patients, our results suggest that for tumors amenable to no ischemia, lack of hilar clamping may reduce the risk of ARF and chronic kidney disease. 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 Fig. 1 Evaluation of new-onset stage IV chronic kidney disease among 297 patients treated with no ischemia and warm ischemia during partial nephrectomy in the setting of a solitary kidney. GFR = glomerular filtration rate. Fig. 2 Evaluation of new-onset stage IV chronic kidney disease among 266 patients treated with no ischemia and warm ischemia during open partial nephrectomy (laparoscopic cases excluded) in the setting of a solitary kidney. GFR = glomerular filtration rate. E UR OP E A N UR OL OGY XXX ( 2 0 1 0 ) XXX XXX 4 EURURO 3489 16 Please cite this article in press as: Thompson RH, et al. Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney. Eur Urol (2010), doi:10.1016/j.eururo.2010.05.048 Kidney Cancer Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney R. Houston Thompson a, *, Brian R. Lane b , Christine M. Lohse a , Bradley C. Leibovich a , Amr Fergany b , Igor Frank a , Inderbir S. Gill c , Steven C. Campbell b , Michael L. Blute a a Mayo Medical School and Mayo Clinic, Rochester, MN, USA b Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA c Keck School of Medicine, University of Southern California, Los Angeles, CA, USA E UR OP E AN UR OL OGY XXX ( 2 0 1 0 ) XXX XXX avai l abl e at www. sci encedi r ect . com j our nal homepage: www. eur opeanur ol ogy. com 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Article info Article history: Accepted May 31, 2010 Published online ahead of print on Keywords: Ischemia Kidney neoplasms Postoperative complications Nephrectomy Warm ischemia Abstract Background: The safe duration of warmischemia 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 identied 458 patients who underwent open (n = 411) or laparo- scopic (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: 455) of warm ischemia. Patients treated with warm ischemia had a signicantly higher preoperative glomerular ltration rate (GFR; median: 61 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 signicantly 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 30 ml/min per 1.73 m 2 , patients with warm ischemia were signicantlymorelikelytodevelopnew-onset stageIVchronickidneydisease(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 PNina multivariable analysis. Limitations include surgeon selection bias when determining type of ischemia. Conclusions: Warm ischemia during PN is associated with adverse renal conse- quences. Although selection bias is present, PN without ischemia should be used when technically feasible in patients with a solitary kidney. # 2010 Published by Elsevier B.V. on behalf of European Association of Urology. * Corresponding author. Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel. +507 284 3981; Fax: +507 284 4951. E-mail address: Thompson.robert@mayo.edu (R.H. Thompson). EURURO 3489 16 Please cite this article in press as: Thompson RH, et al. Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney. Eur Urol (2010), doi:10.1016/j.eururo.2010.05.048 0302-2838/$ see back matter #2010 Published by Elsevier B.V. on behalf of European Association of Urology. doi:10.1016/j.eururo.2010.05.048 Interruption of renal blood flow via pedicle clamping is often necessary during PN, especially for complex tumors with deep parenchymal invasion. Vascular clamping aids in hemostasis and allows precise surgical closure of the collecting system and parenchymal defect. However, pre- dominately exophytic tumors without deep parenchymal invasioncanbeamenabletoenucleationwithout theneedfor hilar clamping. The theoretical concern of hemorrhage or urine leak fromlack of visualization was not observed in the current analysis. Infact, patients treatedwithwarmischemia were more likely to have intraoperative hemorrhage (5% vs 2%) and develop a postoperative urine leak (5% vs 1%) compared with patients treated without hilar clamping, although these differences were not statistically significant. Nevertheless, our results support that the use of no ischemia whentechnicallyfeasibleinproperlychosenpatients will not invite an excess risk of hemorrhage or urine leak. It is, however, important to point out that the majority of renal tumors are not amenable to no ischemia. For these patients, we advocate warm ischemia only if ischemia time is anticipated to be <20 min [3,5,7,8]. For laparoscopic cases, an early unclamping technique was recently reported to significantly reduce ischemia time [13], and robotic assist- ance may further reduce clamping times [14]. In addition, a novel selective vascular occlusion delivered via angiographic techniques was recently observed to hold promise [15]. However, for patients with complex tumors, where ischemic timesareanticipatedtobe>2030 min, strongconsideration shouldbe givento hypothermic conditions withice slush[5]. This study is not without limitations. The data were collected in a retrospective fashion, and our results are limited to the inherent biases associated with this approach. Additionally, there is a significant selection bias when comparing patients treated with no ischemia and warm ischemia. Patients treated with no ischemia were likely to have more exophytic and smaller tumors that were at a reduced risk of complications. However, patients treated with warm ischemia were, for the most part, thought to have tumors that were amenable to <2030 min of ischemia. Coupled with the fact that patients treated with no ischemia had reduced baseline renal function, our results support the use of no ischemia when technically feasible, especially in the setting of a solitary kidney. We do not submit that clamping should be avoided at all costs but rather support the use of no clamping in select patients with a tumor that is amenable to manual compression. 5. Conclusions Warm ischemia during PN is associated with an increased risk of ARF and chronic kidney disease. Although selection biases likely contributed to these results, PN with no ischemia should be used when technically feasible in patients with a solitary kidney. Other measures to protect against ischemic injury, including hypothermia and phar- macologic manipulations, should be studied in an effort to improve renal functional outcomes in this challenging patient population, many of whom require an ischemic interval to facilitate optimal PN. Author contributions: R. Houston Thompson had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Thompson, Lane, Campbell, Blute. Acquisition of data: Thompson, Lane, Lohse. Analysis and interpretation of data: Thompson, Lane, Campbell, Blute, Lohse. Drafting of the manuscript: Thompson, Lane. Critical revision of the manuscript for important intellectual content: Thompson, Lane, Campbell, Blute, Fergany, Gill, Leibovich. Statistical analysis: Lohse. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Campbell, Blute. Other (specify): None. Financial disclosures: I certify that all conicts of interest, including specic nancial interests andrelationships andafliations relevant tothe subject matter or materials discussed inthe manuscript (eg, employment/ afliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents led, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. Acknowledgment statement: The authors acknowledge the late Dr AndrewC. Novick, who operated on a majority of the patients included in this study. References [1] Thompson RH, Kaag M, Vickers A, et al. Contemporary use of partial nephrectomy at a tertiary care center in the United States. J Urol 2009;181:9937. [2] Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitali- zation. N Engl J Med 2004;351:1296305. [3] Thompson RH, Frank I, Lohse CM, et al. The impact of ischemia time during open nephron sparing surgery on solitary kidneys: a multi- institutional study. J Urol 2007;177:4716. [4] Godoy G, Ramanathan V, Kanofsky JA, et al. Effect of warmischemia time during laparoscopic partial nephrectomy on early postopera- tive glomerular ltration rate. J Urol 2009;181:243843, discussion 24435. [5] Becker F, Van Poppel H, Hakenberg OW, et al. Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol 2009;56: 62534. [6] La Rochelle J, Shuch B, Riggs S, et al. Functional and oncological outcomes of partial nephrectomy of solitary kidneys. J Urol 2009; 181:203742, discussion 2043. [7] Thompson RH, Leibovich BC, Lohse CM, Zincke H, Blute ML. Com- plications of contemporary open nephron sparing surgery: a single institution experience. J Urol 2005;174:8558. [8] Lane BR, Babineau DC, Poggio ED, et al. Factors predicting renal functional outcome after partial nephrectomy. J Urol 2008;180: 23638, discussion 23689. [9] RichstoneL, Kavoussi LR. Re:Theimpact of ischemiatime duringopen nephron sparing surgery on solitary kidneys: a multi-institutional study: R.H. Thompson, I. Frank, C.M. Lohse, I.R. Saad, A. Fergany, H. Zincke, B.C. Leibovich, M. L. Blute, and A. C. Novick. J Urol 2007; 178:1119, author reply 111920. [10] Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, Modica- tion of Diet in Renal Disease Study Group. A more accurate method 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 E UR OP E A N UR OL OGY XXX ( 2 0 1 0 ) XXX XXX 5 EURURO 3489 16 Please cite this article in press as: Thompson RH, et al. Comparison of Warm Ischemia Versus No Ischemia During Partial Nephrectomy on a Solitary Kidney. Eur Urol (2010), doi:10.1016/j.eururo.2010.05.048 WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT: BULLDOGS 12.5 Port lap Bulldog No need for extra port Less leaks always tag with vessel loop Less Handcufng 5 1 /1 Fixed applicator for temporary endoscopic vascular clips Shaft length: 34 cm Diameter: 12.5 mm PL531R CLIP APPLICATORS AND REMOVERS ATRAUMATIC ENDO VESSEL CLIPS (for temporary occlusion) Articulating applicator for temporary endoscopic vascular clips Shaft length: 34 cm Diameter: 12.5 mm PL530R 1 /1 Cat. No. Closing force Jaw length Jaw shape PL544S 350 g 25 mm short/straight PL545S 450 g 45 mm long/straight PL548S 350 g 25 mm short/curved PL549S 450 g 45 mm long/curved VASCULAR BULLDOG CLIP AND APPLIERS WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT: BULLDOGS 12.5 Port lap Bulldog No need for extra port Less leaks always tag with vessel loop, stitch ext Less Handcufng Less chance of over tightening WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT: SATINSKI Straight or slight curve easier to use in in port. Flex port available for others Sometimes in the way Leaks Extra post 4 Vascular Clamps for Temporary Occlusion PM171R* Satinsky Atraumatic Clamp, 38mm jaw, 5mm, 31cm PM711R PM973R PM177R* Satinsky Atraumatic Clamp, 51 mm jaw, 5mm, 31cm PM718R PM973R 1/2 PM173R Crafoord Endo-vascular Clamp, short jaw, 5mm, 31cm PM713R PM973R 1/2 Order by component De Bakey Atraumatic Clamp, straight, 50mm Jaw, 10mm, 22cm PM712R PM992R 1/2 PM175R* De Bakey Atraumatic Clamp, curved, 5mm, 31cm PM716R PM973R 1/2 PM176R* De Bakey Atraumatic Clamp, S-shaped, 5mm, 31cm PM717R PM973R 1/2 COMPONENTS COMPLETE JAW INSERT INSULATED STANDARD OPTIONAL INSTRUMENT OUTER TUBES HANDLE HANDLES Optional Handles for Customizing Instruments - Interchangeable for 5mm and 10mm instruments PO958R (Non-Ratchet) PO959R (Ratchet) PM950R (Non-Ratchet) PM951R (Ratchet) PM954R (Ratchet) PM955R (Non-Ratchet) PM957R (Ratchet) with lock Instruments may be ordered COMPLETE or assembled from COMPONENTS ordered separately *For use with 12.5mm flexible Trocars WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT: SATINSKI Faster than bulldogs More likely to incompletely clamp Less precise Fall off, knock off incomplete force at the tip Complex vasculature, less effective 4 Vascular Clamps for Temporary Occlusion PM171R* Satinsky Atraumatic Clamp, 38mm jaw, 5mm, 31cm PM711R PM973R PM177R* Satinsky Atraumatic Clamp, 51 mm jaw, 5mm, 31cm PM718R PM973R 1/2 PM173R Crafoord Endo-vascular Clamp, short jaw, 5mm, 31cm PM713R PM973R 1/2 Order by component De Bakey Atraumatic Clamp, straight, 50mm Jaw, 10mm, 22cm PM712R PM992R 1/2 PM175R* De Bakey Atraumatic Clamp, curved, 5mm, 31cm PM716R PM973R 1/2 PM176R* De Bakey Atraumatic Clamp, S-shaped, 5mm, 31cm PM717R PM973R 1/2 COMPONENTS COMPLETE JAW INSERT INSULATED STANDARD OPTIONAL INSTRUMENT OUTER TUBES HANDLE HANDLES Optional Handles for Customizing Instruments - Interchangeable for 5mm and 10mm instruments PO958R (Non-Ratchet) PO959R (Ratchet) PM950R (Non-Ratchet) PM951R (Ratchet) PM954R (Ratchet) PM955R (Non-Ratchet) PM957R (Ratchet) with lock Instruments may be ordered COMPLETE or assembled from COMPONENTS ordered separately *For use with 12.5mm flexible Trocars WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT: UNCLAMPED Unclamping is a viable option Based on surgeon experience Hilum ready during dissection Can minimize clamp time risk! Thus longer dissection without ischemia WHAT ARE YOUR OPTIONS FOR HILAR MANAGEMENT COMPLICATIONS Vascular Injuries Are Underreported Excluded from case series Complications from Lap Partial are decreasing with time in large series. Planning for NSS Planning for NSS (Part 2: (Part 2: You can do it to You can do it to ) ) Complications Complications Hemorrhage Hemorrhage Renal inIarction / loss Renal inIarction / loss Urinary leak or Iistula Urinary leak or Iistula Abscess Abscess Rates Rates Lap Lap PNx PNx - - 9 9 Open Open PNx PNx - - 6.3 6.3 RFA RFA - - 6 6 Lap Lap RNx RNx - - 3.4 3.4 Open Open RNx RNx - - 1.3 1.3 Partial Nephrectomy Planning: Partial Nephrectomy Planning: Everybody Everybody s doing it, you can to s doing it, you can to Brian R. Herts, MD Brian R. Herts, MD Associate ProIessor oI Radiology Associate ProIessor oI Radiology Head, Abdominal Imaging, Imaging Institute & Head, Abdominal Imaging, Imaging Institute & StaII, The StaII, The Glickman Glickman Urological and Kidney Inst. Urological and Kidney Inst. Cleveland Clinic Cleveland Clinic CLAMPING FORCE: Urologists are not routinely clamping vessels. What can we learn from vascular surgery? Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Vascular clampsendothelium and artery wall interactions: an experimental study in the sheep: A. I. Margovsky et al. characteristics, these studies consistently uncovered endothelial damage and other cellular injuries. The pressures generated by different types of clamps were occasionally measured [3, 4, 10, 13], but no previous studies graded the pressures applied to the vessel wall to the subsequent injury, nor have previous studies investigated clamp-related injuries in relation to differences in artery diameter. Investigators have generally used histological examination and scanning electron microscopy to determine vessel wall damage [1, 2, 5, 8, 9, 11, 12, 15]. Other methods for measuring the extent of injury include the assessment of functional ability [14], vasomotor responses [12] and local platelet uptake [4]. In vivo staining with Evans blue has also proved useful for dening the extent of endothelial disruption [3, 8], especially when a computer- assisted program was employed to calculate the dam- aged areas [16]. This study aimed to investigate the correlation between the forces generated by commonly used vas- cular clamps and the ensuing endothelial and artery wall damage. The carotid and femoral arteries of the sheep were studied in vivo to achieve a reproducible animal model. Materials and methods Experimental protocol Sheep were studied, as the carotid and femoral arteries are of similar calibre to those in man. The carotid and femoral arteries of four adult sheep weighing between 40 and 50 kg were used. A total of 16 arteries were subjected to varying clamp forces and the extent of endothelial damage was assessed by Evans blue staining, histological examination and scanning electron microscopy. Anesthaesia was induced using intravenous Nem- butal (15 mg/kg) and maintained using oxygen with 1.52.5% Halothane. An intravenous line provided uid replacement with normal saline through an external jugular vein. Systemic blood pressure was monitored through a catheter in the deep femoral artery and mean blood pressure was maintained between 90 and 100 mmHg. Both carotid arteries were exposed via a midline neck incision. The femoral arteries were exposed through groin incisions. An aliquot of 150 IU/kg of sodium Heparin was administered intravenously 5 min before the rst set of clamps was applied to the carotid arteries. Four identical angled DeBakey arterial clamps (Downs Surgical, UK) were placed on the middle section of each exposed artery at 1-cm intervals, avo- iding any branches and surrounding tissues, and commencing at the distal end to avoid clamping a collapsed vessel (Figure 1). The jaws of each clamp CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 458 Figure 1 Diagram showing four angled DeBakey vascular clamps applied to the artery with forces generated at (a) three notch, (b) four notch, (c) ve notch and (d) six notch, respectively. t thickness of clamped artery is proportional to the force applied were placed at right angles to the long axis of the vessel, with the vessel held 1 cm from the tip of the clamp. The four clamps were closed to three, four, ve and six notches, respectively, and left in place for 15 min. After the last clamp was removed, a 0.5% solution of Evans blue dye (up to a total volume of 3 ml/kg) was administered intravenously and allowed to circu- late for 30 min [16]. All carotid and femoral arteries were then removed, opened longitudinally and pinned at. The areas of blue staining were exam- ined under a dissecting microscope at 7 magni- cation. A video camera (KP-M1E, HitachiDenshi, Japan) connected to the viewing post of the micro- scope was used to acquire images. The images were transferred to a computer (Apple Macintosh, using Image Scion, version 1.51, National Institutes of Health, USA), which calculated the area of blue staining in each vessel using appropriate calibration. At the end of each experiment, the animals were humanely killed. Half of the samples were then xed in glutaraldehyde and prepared for scanning electron microscopy (Stereoscan S150, Cambridge Instru- ment CO, UK). The rest of the arterial specimens subjected to clamping were xed in 10% buffered formalin. The morphological changes were studied after staining the parafn sections with haematoxylin and eosin. Clamping force and pressure measurements Before the clamps were applied, the closing force for each notch of the DeBakey angled vascular clamps employed in this experiment was pre-measured by an electronic loading-cell device with 0.1 N resolution CLAMPING FORCE: Excessive clamping force can injure the renal artery. Ratcheting forces on satinski can be over applied more than bulldogs, active vs passive force Minimal force should only be applied There can be a lot of surgeon tension, dont let that translate to a vascular injury Lump of coal to diamond in sphincter syndrome Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Vascular clampsendothelium and artery wall interactions: an experimental study in the sheep: A. I. Margovsky et al. using the following procedure (Figure 2) where: A electronic load-cell measured force to 0.1 N resol- ution; and B electronic digital callipers measured distance to 0.01 mm resolution. For a given notch setting D refers to the displace- ment of the application point of the callipers. The force from the load cell (A) was correlated with the gap between the jaws of the arterial clamp (C) as measured by the gauge (B). The procedure was repeated for a range of gaps with the displacement determined by the screw thread (E). At any notch setting, ve different loads were applied giving a load in newtons (N)/deection (t mm) ratio for that notch setting. The measure- ments were repeated three times for each notch set- ting giving a family of curves. Using a statistical curve tting software package (Microsoft Excel 4.0) one empirical function was derived to obtain the gap thickness (deection) in terms of the two variables: No (the notch settings) and F (force). The family of curves was then replotted using this derived math- ematical function to ensure agreement with the orig- inal experimental data (Figure 3). The external diameters of the arteries and the thickness of the clamped arteries were measured using callipers. These measurements were used to calculate the average forces generated by the clamps, using the equation: F t (5.9957 1.4688 No) 0.4163 0.0172 No where: F force applied (newtons); t clamped thickness (mm); No notch number. The areas subjected to clamp application were cal- culated using the equation: A D (mm) 3 mm, where: A area of the clamped artery; D external Figure 2 Diagram showing setup for electronic loading-cell measure- ments of forces generated by clamps (explanation in text) CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 459 Figure 3 Diagram showing computer-analysed correlations between the clamped thickness and forces generated by DeBakey vascular clamp diameter of clamped artery; 3 mm width of the angled DeBakey vascular clamp. To calculate the specic compressive pressure (P) immediately under the clamp face, the estimated clamping force was divided by the compressed area, which is related to the area of the clamp face as fol- lows: P F/A, where: P pressure (newtons/mm 2 ); F force (newtons); A area of the clamped artery (mm 2 ). All the surgical and technical procedures were per- formed at the Department of Biomedical Engineer- ing of the University of NSW, with approval from the local Animal Care and Ethics Committee (ACEC). The data were analysed using the Wil- coxon signed-rank non-parametric statistical test. Values are shown as mean s.d. Results Clamping force and pressure measurements The mean external diameters were 7.2 0.8 mm for carotid arteries and 5.3 0.7 mm for femoral arteries. The clamping forces generated by the standard angled DeBakey vascular clamps were calculated for carotid and femoral arteries in relation to the thick- ness of the vessel clamped (Table 1). The mean area (mean s.d.) subject to clamp application in the carotid arteries was 67.86 7.5 mm 2 for carotid arteries and 49.95 6.5 mm 2 for the femoral arteries. The results of the specic compressive pressures were expressed as mean s.d. (Table 2). Other vari- ables, including systemic blood pressure and vessel elasticity, were not included in the calculations because all measurements were performed under Vascular clampsendothelium and artery wall interactions: an experimental study in the sheep: A. I. Margovsky et al. Figure 5 Scanning electron microscopy images at the sites of clamps application: a, b, c, d femoral artery (original magnication 25); e, f, g, h carotid artery (original magnication 25); a, e three notch; b, f four notch; c, g ve notch and d, h six notch In mild injuries, light microscopy analysis did not identify any signicant endothelial injury and the internal elastic lamina was intact. However, vacuoliz- ation of some smooth muscle cells in deep medial areas was observed in some specimens (Figure 6A). In moderate injuries, vacuolization of smooth muscle cells in the media was consistently detected. The internal elastic lamina was partially disrupted in ssures and the adjacent endothelial cells showed denite signs of injury within the ssure zone with- out extensive desquamation of the cells around the clamped site (Figure 6B). In severe injuries, the cell response was different compared with moderate injury, including complete desquamation of the endothelial cells in the zone of clamp application. Vacuolization of smooth muscle cells in the supercial and deeper part of media was CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 461 apparent. Continuity of the internal elastic lamina was broken in the ssure zone, with the ssure usu- ally extending through the medial layer to form a cavity often lled with thrombus (Figure 6C). Discussion Numerous reports conrm that vascular clamps can damage the vessel wall [1, 3, 57, 12, 1719]. Most of these studies evaluated different vascular clamps in a general way with relatively few analysing the effects of specic features of clamp design. Clamp geometry, closing force, weight and holding ability are known to inuence the extent of trauma. The architecture of the jaw face [3, 8, 10], the type of vessel [15] and the duration of clamping are also important. In the present study, the extent of endo- CLAMPING FORCE: Excessive clamping force can injure the renal artery. Ratcheting forces on satinki can be over applied more than bulldogs, design. Minimal force should only be applied There can be a lot of surgeon tension, dont let that translate to a vascular injury Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Cardiovascular Surgery, Vol. 7, No. 4, pp. 457463, 1999 ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 09672109/99 $20.00 0.00 www.elsevier.com/locate/cardiosur PII: S0967-2109(98)00154-9 The effect of increasing clamping forces on endothelial and arterial wall damage: an experimental study in the sheep A. I. Margovsky, A. J. Chambers and R. S. A. Lord Surgical Professorial Unit, St Vincents Hospital, University of NSW, Sydney, Australia Purpose: This study aimed to relate the level of physical force applied to the arterial wall by atraumatic clamps to the degree of endothelial and wall damage. Methods: Sixteen sheep carotid and femoral arteries were each demarcated into four segments 1 cm apart (total 64 segments). Each segment was clamped for 15 min with a standard angled DeBakey vascular clamp. Four levels of force were generated by closing the clamp at three, four, ve and six notches of closure. The extent of endothelial injury was assessed by using a dedicated com- puter assisted image acquisition program to measure the area stained by Evans blue dye. The extent of damage to the layers of the arterial wall was analyzed and compared by scanning electron microscopy and light microscopy. Results: For femoral arteries, the area of endothelial injury was considerably less for three notch (3.76 0.28 newtons) and four notch (5.68 0.29 newtons) closure compared with that for ve notch (6.19 0.31 newtons) and six notch (6.61 0.16 Newtons) closure (p 0.01). For carotid arteries, three notch (5.68 0.28 newtons) closure caused less damage than did four notch (7.98 0.29 newtons), ve notch (9.17 0.40 newtons) and six notch (9.57 0.64 newtons) closure (P 0.02). Scan- ning electron microscopy conrmed the extent and depth of arterial injury corresponded directly to the forces generated by the vascular clamps. Conclusions: The closing forces gener- ated by arterial clamps correlated positively with the extent of artery wall injury. Vascular clamps should be applied at the minimum level of force that will arrest blood ow. ! 1999 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved Keywords: arterial wall, endothelial wall, sheep, vascular clamp Introduction Clamps are used to arrest ow and to control bleed- ing from arteries [1], but they may also cause moder- ate to severe damage to the vessel wall [24], which could jeopardize an otherwise successful vascular reconstruction. Some of these complications, such as creation of a ap, dissection, through-and-through injury and arterio-venous stulae follow relatively gross instrumentation. Other effects, including intra- Correspondence to: Professor Reginald S. A. Lord, Surgical Prof- essorial Unit, Level 17, OBrien Building, St Vincents Hospital, Vic- toria Street, Darlinghurst, NSW 2010, Australia CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 457 vascular thrombosis and later stricture formation [5, 6], reect more subtle injuries including endothelial disruption [7]. Previous reports described some of the features of clamp design and the effects of different clamps on the vessel wall. These studies concentrated parti- cularly on relating available vascular atraumatic clamps in terms of their occlusive ability and holding capacity to the effect on the vessel wall [13, 5, 8 11]. In some of these reports, the arteries studied were relatively small, such as rat and rabbit aortas, and femoral arteries [5, 1214]. In other studies, canine arteries were employed [2, 3, 8, 9, 11]. Despite the differences in arterial diameters, wall thickness, lamellar units and other morphological Vascular clampsendothelium and artery wall interactions: an experimental study in the sheep: A. I. Margovsky et al. Figure 6 Light microscopy showing damage of the sheep carotid artery upon clamp application (original magnication 100). (A) Mild damage, (B) moderate damage, (C) severe damage thelial disruption has been directly correlated with increasing forces of clamp application, with the study design limiting the effect of other variables including the duration of clamping [16]. A sheep model was used in this investigation because ovine carotid and femoral arteries are com- parable in size to those in man. Standard angled DeBakey clamps were chosen because these clamps are commonly used in human vascular procedures. These clamps are similar to other serrated clamps that, in general, have proved to be most reliable and resistant to slipping. A further reason for using the DeBakey clamp in our study was that the DeBakey clamp ranked as average among other vascular atraumatic clamps [2]. The force needed to occlude a vessel is determined by four variables: vessel diameter, blood pressure, vessel elasticity and blade contact area. The closing pressure of clamps used to occlude small calibre ves- sels has been estimated [13], but the precise relation- ship between the forces generated by the clamp, the actual closing pressures, and the subsequent arterial wall injuries have not been quantied. Berlin and Berlin [10] established that com- pression forces of 50 to 75 g are needed to arrest ow in a vessel under 300 mm pressure. Most of the widely used vascular clamps examined, however, required 200 to 1000 g or even greater force to engage the latches [10]. Harvey and Gough [8] demonstrated that when a clamp was applied with sufcient force to occlude a vessel, the damage was considerably less than when the clamp was fully closed [8] and Pabst et al. [20] conrmed that excessive clamping forces caused sev- ere endothelial damage. In the present experiment, the forces generated at CARDIOVASCULAR SURGERY JUNE 1999 VOL 7 NO 4 462 three-notch clamping induced a signicantly smaller area of endothelial disruption than forces generated at four, ve and six notches. The area of damage reached a maximum level at ve notches, beyond which there was no further signicant change. The results indicate that damage to endothelium depends on the closing pressure of the specic clamp within a limited range, but increases in pressure beyond this have no additional effect on the endothelium. This observation may relate to blood vessels being viscoel- astic and thus sharing some of the characteristics of viscous liquids, namely, continuous deformation after a force is applied. Scanning electron microscopy demonstrated a direct relationship between vascular compressive forces and arterial wall damage. Higher magni- cation revealed deposition of platelets on the surface proportional to the endothelial lesions, but there was little evidence of thrombogenesis, perhaps because of the brief duration of clamp application. The minimal endothelial damage produced by forces generated at three-notch clamping suggests that effective occlusion of arteries 4.58 mm external diameter can be performed safely at this level of clamp closure. However, the amount of damage caused will be additionally inuenced by vessel size, systemic blood pressure, clamp jaw geometry, arterial wall elasticity and the duration of clamp application. Evans blue dye injected intravenously stains dam- aged endothelial cells, and this property has proved reliable in outlining the areas of clamp application [12]. The authors rened the use of Evans blue staining by a new method of computer-assisted analysis to achieve precise calculation of the dam- aged surface. Using this and other technology the OTHER MEANS OF CONTROL Vessel loop tourniquet Pre made on the bench Less Clamping force ?? Operator dependant OTHER MEANS OF CLAMPING Temporary Hemolocs on the artery Non red vascular stapler Not ideal, clamping force uncontrolled You are really doing a nephrectomy !!! high risk of injury Aberant Vessels Arterial anatomy Arterial anatomy Venous anatomy Venous anatomy Circumaortic leIt renal vein Retroaortic leIt renal vein Tumor position Tumor position Four renal segments, based on vascular territories Four renal segments, based on vascular territories apical anterior basilar posterior CASE STUDY 53 yo man presents with the above CT after an emergency visit for central abdominal pain. Pain settled, US normal except solid left renal mass CASE STUDY Mass is considered for biopsy but you decide that it wont change your management. Its 3.3cm solid enhancing, well circumscribed, 70% exophytic lateral mid polar, without nodes. CT chest normal. Hilum shows a single artery and vein Management? CASE STUDY Lap Left partial Clamp? Clampless? Technique. You go with Satinski. Blood loss100 cc, clamp time 13min Surgery goes well, you pat yourself on the back (a hero in your own mind), Beers taste good that evening. CASE STUDY Day 2 he develops Nausea and an ileus. You think he should be going home. Bloodwork. CBC, Lytes BUN Cr, LFTs and LDH Hb 134 Cr 140 (84 preop) AST 1.5Xnormal LDH 2Xnormal You order a Renogram to avoid dye CASE STUDY HILAR MANAGEMENT The current standards of Bulldogs or Satinky are not without aws Satinski can slip off or incompletely occlude but can be quick and require less meticulous hilar dissection Bulldogs require the vessels dissected clean which can lead to inadvertent injury or bleeding Dissection of the renal artery or atheroclerotic embolic events can occur and are underreported. Renal artery stenosis has been reported associated with hypertension post arterial clamping Excessive force of vessel loops can injure vessels. All methods of control need careful application of force to the minimal requirement Unexpected bleeding due to an unrecognized arterial unclamped branch should NOT mean more pressure on the clamp Incomplete occlusion of the artery with an occluded vein can lead to infarction from venous congestion, hemorrhage or poor visibility and poor renal defect closure USE THE TECHNIQUE THAT YOU ARE COMFORTABLE WITH TREAT THE VESSELS WITH CARE WHEN CLAMPING BULLDOGS ARE ARGUABLY LESS RISKY DUE TO THE PASSIVE FORCE SATINSKI REQUIRES AN EXTRA PORT PLACED CAREFULLY OUT OF THE WAY, BUT ARE QUICK VESSEL LOOPS ARE AN ALTERNATIVE CLAMPLESS IS THE ONLY TECHNIQUE WITHOUT ISCHEMIA CLAMP TIME IS CRITICAL WITH PRECISE SURGERY CLAMPLESS ALLOWS SLOWER NON ISCHEMIC MICRO DISSECTION, APPEARS TO BE ON THE RISE. Conclusion ABERRANT ANATOMY? CLAMP ARTERY ONLY TO AVOID VENOUS CONGESTION. SEGMENTAL ARTERY ONLY, WITHOUT VEIN IF BLEEDING WHEN CLAMPED, DO NOT CRANK RATCHET EXCESSIVELY, ITS PROB AN ACCESSORY VESSEL. TAG ALL BULLDOGS, ITS NO FUN LOOKING FOR ONE THAT HAS FALLEN OFF DO YOU NEED MORE THAN ONE TOOL FOR HILAR CONTROL. EFFECTIVE USE OF BULLDOGS OR SATINSKI, VESSEL LOOPS OR HAND PORT Conclusion ADVANCED LAPAROSCOPIC AND ROBOTIC UROLOGY SKILLS FORUM ENUCLEATION VS. EXCISION: MAINTAINING TUMOUR MARGINS Christopher French MD FRCSC Genitourinary Oncology/ Endourology Eastern Heath, Memorial University of Newfoundland June 2014 STANDARD PARTIAL NEPHRECTOMY VS ENUCLEATION thickness of 1 mm (range: 0.381.6) laying beyond the tumor pseudocapsule with signs of chronic inflammation [21]. This precious microscopic layer of renal parenchyma allows the presence of negative surgical margins also in patients with tumors extending beyond the pseudocapsule (Fig. 1). Taking into account the minimum thickness of the safety margin in the most recent NSS series, it is probable that in a significant percentage of cases the margin that resulted was 1 mm, substantially similar to the one reported by Minervini et al after simple enucleation [10,11,1316,21]. Therefore, sim- ple enucleation can be considered a safe technique, in perfect harmony with the EAU guidelines, which only recommend the presence of a minimal tumor- free surgical margin of healthy tissue in order to reduce the risk for local relapse [1]. Nevertheless, the study by Minervini et al raises new questions that will probably be solved in the future. From the surgical point of view, simple enuclea- tion is performed through an incision of the renal parenchyma at 12 mm from the neoplasia and through the blunt development of a space between the tumor pseudocapsule and the normal renal tissue, without any visible healthy parenchyma surrounding the tumor [1]. Starting from this assumption, how can we explain the presence of a 1-mm margin of kidney parenchyma around the pseudocapsule? Is it possible to think that the thickness of the healthy tissue surrounding the tumor is larger where the pseudocapsule is infil- trated by the tumor? Waiting for further studies confirming Minervini et als results [21], we believe it is only possible to formulate hypotheses. For example, the presence of chronic inflammation in the healthy tissue around the tumor could justify a stronger adhesion to the pseudocapsule, causing its involuntary removal during simple enucleation. This inflammation could be a direct consequence of the compression of the tumor on the healthy parenchyma or of a neoplastic infiltration of the pseudocapsule. To further inves- tigate this aspect, it could be useful to explore the correlations between the thickness of the tissue surrounding the neoplasia and the tumor size or the extension of the pseudocapsular infiltration. Even though the scientific attention is mostly focused on the parenchymal side of the tumor, the study by Minervini et al [21] highlights the impor- tance of the risk of infiltration also on the adipose slope of the tumor. Although less frequent than the parenchymal infiltration, from the oncologic point of view, the involvement of the perirenal fat has an Fig. 1 (a) Traditional partial nephrectomy with excision of an adequate additional margin of peritumor renal parenchyma (410 mm); (b) minimal partial nephrectomy with excision of a 1-mm safety margin. e ur op e an ur ol og y 5 5 ( 2 0 0 9 ) 1 3 1 5 1 3 2 0 1317 STANDARD PARTIAL NEPHRECTOMY As pioneered by Novick (open) Objectives are for complete tumour removal While preserving the largest part of healthy parenchyma Generally tumours less than 4cm requires closure/repair of calyces, central vessels Minimize vascular compromise of healthy remainder of kidney and Minimize warm ischemia STANDARD PARTIAL NEPHRECTOMY Pros Wide excision gives pathologist rim of healthy tissue This healthy rim should benet the patient Similar to open technique Less ambiguous pathology reports Our Traditional Training and comfort zone Less anxiety re Patient and Surgeon for follow up STANDARD PARTIAL NEPHRECTOMY Cons Can be more complicated Leaks, AVF, bleeding risks More difcult Lap Repair of defect longer warm ischemia ? No true surgical planes All factors that compromise the healthy remainder of kidney SIMPLE TUMOUR ENUCLEATION Terminology Super Selective Microdissection Minimal partial nephrectomy What is the Margin of safety? MARGIN OF SAFETY UROPEAN UROLOGY 55(2009) 1315-1320 presence of adjacent nodular areas, the percentage of tumor deepened into the kidney, and the relationships with the urinary collecting system. Currently, the impact of these factors on the thickness of the safety margins surrounding the resected tumor during partial nephrectomy has been scarcely addressed. The further emerging information is that the thickness of the parenchyma surrounding the tumor does not influence the long term progression-free survival in patients with negative surgical margins [16]. This informationhas beenacknowledgedby the most recent version of the European Association of Urology (EAU) guidelines recommending the pre- sence of a minimal tumor-free surgical margin of healthy renal parenchyma surrounding the resected tumor in order to reduce the risk of local relapse or progression, without specifying the exact minimum thickness to be taken [1]. In this scenario, simple enucleation has found a growing number of supporters as NSS for small RCC. This surgical technique consists of the incision of the renal parenchyma within a few millimeters from the tumor and the blunt dissection of a plan between the pseudocapsule of the tumor and the normal renal tissue without the inclusion in the removed tissue of any visible normal renal par- enchyma. Even though the simple enucleation might be correctly used in patients with bilateral kidney tumors and/or with solitary kidneys preserving most parenchyma possible, its use in patients with single tumors and contralateral normal kidney is more controversial considering the higher risk of local recurrences, particularly in patients with neoplastic infiltration of the tumor pseudocapsule [7,12,17]. Despite this skepticism, literature data show that simple enucleation provides oncologic results simi- lar to the conventional NSS. In a series of 232 patients who had undergone simple enucleation for 4 cm RCC, Carini et al reported 5-yr and 10-yr cancer-specific survival rates of 96.7% and 94.7%, respectively. Moreover, the authors observed no case of positive surgical margins or recurrence at the initial site of the tumor after a mean follow-up of 76 mo [18]. The absence of positive surgical margins should let us hypothesize the absence of neoplastic infiltration beyond the tumor pseudocapsule. This theory is inconflict with literature data, reporting an infiltration of the tumor pseudocapsule in percen- tages ranging between 15% and 100% [17,19,20]. In the current issue of European Urology, Minervini et al report the results of anaccurate histopathologic analysis on 90 consecutive patients who had under- gone simple enucleation for T1a RCC between 2006 and 2007 [21]. The prospective design of the study and the pathologic methodology allowed the authors to obtain a set of original morphological data on the status of tumor pseudocapsule and surgical margins in patients who had undergone simple enucleation. The thickness of tumor pseu- docapsule ranged between 0.04 mm and 0.79 mm. A neoplastic pseudocapsule infiltration was reported in 33% of cases. In detail, the parenchymal side of the pseudocapsule was involved in 26.6% of cases, while the extrarenal adipose side was infiltrated in 6.6% of cases. The pseudocapsule infiltration was more frequent in patients with larger tumors, higher nuclear grading, or coagulative tumor necrosis. Similar to most partial nephrectomy series, 14% of patients showed a neoplastic infiltration beyond the pseudocapsule toward the renal parenchyma. How is it possible to find and explain negative surgical margins in this group of patients after a simple enucleation? The most original data from Minervini et al consist of the description of a tissue with a median Table 1 Summary of the most recent data from the literature: analysis of the mean, minimum, and maximum values of the safety margin of healthy tissue around the tumor during partial nephrectomy Study Cases Safety margin Indications Mean value, mm Range, mm Piper et al [10] 67 4.5 112 A safety margin <1 mm is sufcient. Sutherland et al [11] 41 2.5 0.57 A minimum safety margin (25 mm) is sufcient. Castilla et al [16] 69 3.5 0.59.5 The extension of the safety margin is not related to disease progression in patients with negative surgical margins. Berdjis et al [13] 121 5 123 No correlations between safety margins and disease progression/local relapse. Timsit et al [14] 61 Cortical: 7 410 Tumor localization and its more or less intraparenchymatous penetration sometimes render difcult a safety margin of 1 cm. Bottom: 2 05 Li et al [15] 115 Cortical: 4.5 46 A <5-mm safety margin is sufcient. Bottom: 2.2 06 e ur op e a n ur o l og y 5 5 ( 2 0 0 9 ) 1 3 1 5 1 3 2 0 1316 SIMPLE TUMOUR ENUCLEATION Pros Debatable, but any margin in a T1a renal mass is safe. Surgical plane allowing blunt dissection Deep margin resection avoids larger vessels Avoids calyx Less complex closure less risk of delayed complications since less calyx entry less normal parenchyma removed. Less risk of ischemic normal tissue less bleeding Amenable to clamp less technique SIMPLE TUMOUR ENUCLEATION Cons Requires very clear visibility Easy to enter tumour capsule Cystic masses can be very difcult Multifocality 10% requires communication with pathologist Irregular borders/inammatory tumours more extensive fat dissection off tumour Not for T2 or high grade tumours Unclamped Hand-Assisted Laparoscopic Partial Nephrectomy for Predominantly Endophytic Renal Tumors Jason D. Engel, 1 Stephen B. Williams 2 Urology Journal Vol 10 No1 Winter 2013 769 Vol. 10 | No. 1 | Winter 2013 | UROLOGY JOURNAL Unclamped Hand-Assisted Laparoscopic Partial Nephectomy | Engel and Williams lows the inherent pyramidal anatomy to a single artery at its base. This artery is pinched oII between the thumb and index fnger, allowing Ior immediate removal oI the tumor Ior thor- ough pathologic examination Ior tumor type and adequacy of margins. As long as the plane has not been forced in any way, hemostasis, even at this point, is generally excellent with only a Iew points oI bleeding at the base oI the deIect. A single fnger can generally be gently placed in the deIect to hold pressure. II cortical bleeding occurs as well, this is eas- ily managed by manual compression of the defect. Bleeding is compressed Ior a Iull ten minutes, which occurs during pathologic analysis of the specimen. In the setting of negative margins, no further resection is per- formed. If there is a positive margin, or if there is clinical suspicion oI inadequate resection despite negative margins, careIul inspection oI the deIect can be perIormed with little blood loss to guide further resection. Nephrectomy is per- Iormed where there are multiIocal positive margins or where deeper resection is not safe or feasible. Bulldog clamps may be applied at this point if a more aggressive standard laparos- copy or open partial nephrectomy is deemed feasible. AIter checking Ior collecting system leaks with a retrograde Figure 1. Computed tomography scan revealing a 2.2 cm enhancing lesion in the anterior mid-pole and a 1.6 cm enhancing lesion in the postero-medial lower pole. Figure 2. The lesion before and after enucleation with use of the fnger fracture technique. NEPHRON SPARING CARINI ET AL 2009 40 E U R O P E A N U R O L O G I C A L R E V I E W Renal Cell Carcinoma Between January 2000 and June 2008, 269 patients had kidney surgery for pathologically confirmed pT1a RCC of whom 240 (89.2%) had NSS and 29 (10.8%) had RN. The number of NSS performed in our department for clinically T1a tumours has increased over time due to increasing surgical experience and better understanding of the technique. The ratio between NSS and RN has changed from 3:1 in the period between January 1986 and December 1999 to 9:1 in the period January 2000 to June 2008 (see Figure 2). Several papers have shown that NSS can be safely performed using a laparoscopic approach and could represent a viable alternative to open NSS with the goal of decreasing post-operative pain and speeding up the return to normal activities. Laparoscopic partial nephrectomy (LPN) has been shown to have intermediate oncological outcomes similar to those of open NSS. 13 A recent multi-institutional survey from 17 centres in the US and Europe, with 855 laparoscopic cases, using LPN for tumours <4cm showed an overall incidence of positive margins of 2.4%. This demonstrated that the oncological efficacy of LPN is comparable to that of open partial nephrectomy. 14 A recent comparison of the intra-operative, post-operative and oncological data of 771 LPN and 1,028 open NSS procedures collected from three large referral centres in the US concluded that equivalent functional and early oncological outcomes can be achieved with these two approaches. 15 Warm ischaemia time should always be limited to 2030 minutes, and these rules should also apply for LPN. Rocca-Rossetti et al. 16 studied 30 kidneys removed after 1560 minutes of warm ischaemia. Ultra-thin sections, using light and electron microscopy, showed distinct changes appearing mainly in the proximal tubules after ~20 minutes with rapidly increasing signs of cellular degeneration at 30 minutes. Independent of the preferred approach, the adoption of a conservative strategy for treating renal masses 4cm may reduce the incidence of RN for pathologically diagnosed benign lesions. In our department, during the period January 2000 to June 2008, 295 patients had NSS for tumours 4cm and of those 14.9% were diagnosed as benign lesions. The incidence of benign lesion was even higher in the paper by Frank et al., who evaluated 2,770 patients who had RN or NSS for sporadic, unilateral, non-metastatic, solid renal masses and found that 23% of renal tumours <4cm were benign. 17 Nephron-sparing Surgery for Intracapsular Renal Tumours >4cm NSS is widening its horizons to expand its indications to tumours >4cm, supported by the concept, reported by several recent papers, that multifocality is not directly related to a tumours greatest dimension. 1821 Lang et al. reported an incidence of multifocality for tumours 4cm and 7cm of 12.9 and 10.9%, respectively, showing no significant correlation between multifocality and tumour size. 20 DiMarco et al. retrospectively reviewed the pathological features associated with multifocality in a series of 2,373 patients treated by RN. 21 The incidence of multifocality in the pT1a and pT1b RCCs (clear cell and papillary cell subtypes, taken together) was 6.4 and 2.2%, respectively. A possible explanation for these findings can be found in an excellent retrospective review on 1,970 RCCs from the Mayo Clinic. 17 The authors found that each 1cm increase in tumour size was associated with a 17% increase in the odds of clear cell compared with papillary RCC. For smaller tumours (<4cm), the incidence of clear cell and papillary cell subtype was 66.3 and 30.6%, respectively. For tumours 47cm in size, the incidence of clear cell subtype increased to 82.7% and of papillary subtypes decreased to 14.1%. 17 The papillary histological subtype is the most accredited risk factor for multifocality along with peri-nephric invasion (pT3a). The indications for elective open NSS should be expanded to include all intracapsular renal tumours regardless of tumour size. A few studies published to date have specifically evaluated the role of open NSS for the treatment of RCC up to 7cm in greatest dimension (see Table 1) and have shown that these tumours behave in a more aggressive way than pT1a, yielding a poorer prognosis. Cancer-specific survival is not related to the type of surgical procedure used (NSS versus RN). 12,2227 Figure 1: Evaluation of Incidence Distribution of Nephron-sparing Surgery and Radical Nephrectomy, January 2000 to June 2008 0 140 RN NSS 120 110 80 60 40 47 33 29 61 49 102 87 115 28 52 20 20002001 20022003 20042005 20062007 2008 Figure 2: Evaluation of Incidence Distribution of Nephron-sparing Surgery and Radical Nephrectomy in Relation to Tumour Stage*, January 2000 to June 2008 0 300 RN NSS 250 29 240 55 51 20 11 200 150 100 50 pT1a pT1b pT2 NSS = nephron-sparing surgery; RN = radical nephrectomy. *pT1a, pT1b and pT2 renal cell carcinoma. NSS = nephron-sparing surgery; RN = radical nephrectomy. Laparoscopic partial nephrectomy has been shown to have intermediate oncological outcomes similar to those of open nephron-sparing surgery. Minervini_subbed.qxp 16/3/09 12:00 pm Page 40 LAPAROSCOPY IS NOT OPEN SURGERY Unique surgical environment C02 15mm, brief rises to 20 are felt to be safe Venous pressure 8-15mm High Magnication and visibility Specic surgical techniques, sliding clip repair, no knots hemostatic agents developed along side lap implementation Surgical tactile feedback maintained Should laparoscopy emulate what we do open? NEPHRON SPARING MARGINS AND STAGE CARINI ET AL 2009 surgery by comparing the results of PN versus RN in contemporary series of renal tumors >4 cm. Patard et al compared the specific survivals of two groups of T1T2 tumors treated either by PN (n = 379) or by RN (n = 1075) [5]. In patients treated by PN, the cancer deathrate was higher for tumors >4 cmcomparedto tumors 4 cm(6.2%vs. 2.2%, respectively). However, in the population of tumors >4 cm, disease-specific survival was not significantly different whether treated by PN or RN (6.2% vs. 9%, p = 0.8). Moreover, local and distant recurrence rates were comparable for larger and smaller tumors (3.6%and 7.1%vs. 2.3% and 15.6%, p = 0.5). Likewise, the group from the Mayo Clinic compared 60 patients with T1b tumors treated by PN to 534 patients with identical tumors treated by RN [6]. Their study included control groups of T1a tumors for each procedure. When adjusting for stage, grade, histologic subtype, and necrosis, no statistical difference concerning sur- vival was noted. However, neither of the two series distinguished between elective and necessary PN. Recently, a multicenter study including >700 elec- tive PNs showed that inthis highly selective group of patients, there was absolutely no difference interms of specific survival between tumors 4 and >4 cm [7]. Since then, numerous published series have confirmed the excellent survival outcome of patients with T1b renal tumors treated by elective PN(Table 1). Mitchell et al matched every patient of a group of 33 T1b RCC treated by PN to two patients with comparable tumors treated by RN. They showed that surgical technique did not affect survival and recurrence [8]. The analysis of a prospective series of 196 patients led Dash et al to the same conclusion [9]. Carini et al reported 71 tumorectomy procedures for renal lesions between 4 and 7 cm (including 31 pT1b tumors) with good oncologic outcomes [10]. However, survival for T1b tumors (83% at 5 yr) was inferior to those published in previous series although it was not significantly different from that of T1a tumors in this study ( p = 0.25). It should be noted that this series included mandatory PN and that the patients who died in the group of T1b tumors exhibited distant and not local recurrences, illustrating that oncologic outcomes are primarily driven by tumor biology rather than surgical technique (as long as a complete tumor excision is achieved). In another study, Becker et al reported excellent cancer control with very long- term follow-up (86.7% specific survival at 15 yr) in patients treated by PNfor tumors >4 cm[11]. Finally, in this issue of European Urology, Antonelli et al analyzed the outcomes of patients with renal tumors >4 cm treated by PN (n = 57) or RN (n = 346) [2]. Their study also included a T1a control group. Overall, they found increased progression and inferior survival rates for larger tumors. However, the type of surgery (PN or RN) did not have any significant impact on the results. Interestingly, in the larger tumor group, with a mean follow-up of 72 mo, the meanlocal recurrence rate was only 1.7%. 4. Widening the indications of PN: impact on surgical morbidity Raising the cut-off size for PN may be limited by an increase in morbidity. In a recent multicenter study by Patard et al, PNfor tumors >4 cmresulted inmore perioperative bleeding, higher transfusion rates, and a higher incidence of postoperative urinary fistulae than PN for tumors 4 cm. Still, this greater morbidity remains acceptable because the global rate of medical and surgical complications as well as length of stay did not differ between the two groups [7]. Table 1 Studies assessing oncologic control following nephron-sparing surgery in relation to tumor size >4 or =4 cm Authors No. of patients and pT stage Comparison between radical and partial nephrectomy Elective vs. imperative indication Mean follow-up, mo % local recurrence % death from cancer Patard et al [5] 65 (pT1b only) Yes Elective and imperative 51 3.6 6.2 Leibovich et al [6] 91 (30 pT1a, 60 pT1b et 1 pT3a) Yes Elective only 106 5.5 3.3 Carini et al [10] 71 (30 pT1a, 31 pT1b, 10 pT3, simple enucleation) No Elective and imperative 74 4.2 12.7 Becker et al [11] 69 (62 pT1b, 4 pT2, 3 pT3a) No Elective only 74 1.4 0 Dash et al [9] 45 (41 pT1b and 4 pT3) Yes Elective only 21 2.2 / Mitchell [8] 33 (21 pT1b and 12 pT3 ou +) Yes Elective and imperative 34 3 3 Patard et al [7] 81 (pT1b only) No Elective only 36 1.3 2.7 Antonelli et al [2] 57 (T1b, T3a) Yes Elective and imperative 72.1 1.7 / e ur op e a n ur o l o g y 5 3 ( 2 0 0 8 ) 6 9 1 6 9 3 692 SURGEONS CRITERIA FOR LAP PARTIAL: TUMOUR lap Partial is operator dependant. Time and efciency are critical!!! Complexity of cases should only increase with experience Dene your criteria! 1.5 - 3cm, >50% exophytic, polar or peripheral, solid and smooth normal opposite kidney, hand assist up to 4cm, min 30% exophytic, non hilar, solid, normal opposite kidney, no BMI limit, hand assist if necessary. SURGEONS CRITERIA FOR LAP PARTIAL: TECHNICAL Closure: Running sliding hemoloc, Hemoloc clip preloaded on loop of barbed suture, Floseal, Snow, gel foam ready. Anchor stitch in parenchyma before clamp. Plan ahead Consistant assistant Prepare Scrub nurse for the next step while completing current Time and Accuracy of dissection CASE STUDY 42 yo lady, with history of melanoma, has multiple UTIs Renal US imaging suggests complex cyst with calcication CT ndings CASE STUDY CASE STUDY Working Dx Complex cyst with stone may be benign calyces diver tic Decision, lap partial Amenable to minimal lap partial? Cystic component, risk of rupture and loss of planes. Deep border irregular. How would you approach this? CASE STUDY Clamp vs unclamp ? Enucleation vs Standard Partial ? Is this case in your criteria? Path? CASE STUDY CASE STUDY CASE STUDY Approach? Partial vs Rad Lap vs Open Clamp vs non clamp Standard Partial vs Enucleation thickness of 1 mm (range: 0.381.6) laying beyond the tumor pseudocapsule with signs of chronic inflammation [21]. This precious microscopic layer of renal parenchyma allows the presence of negative surgical margins also in patients with tumors extending beyond the pseudocapsule (Fig. 1). Taking into account the minimum thickness of the safety margin in the most recent NSS series, it is probable that in a significant percentage of cases the margin that resulted was 1 mm, substantially similar to the one reported by Minervini et al after simple enucleation [10,11,1316,21]. Therefore, sim- ple enucleation can be considered a safe technique, in perfect harmony with the EAU guidelines, which only recommend the presence of a minimal tumor- free surgical margin of healthy tissue in order to reduce the risk for local relapse [1]. Nevertheless, the study by Minervini et al raises new questions that will probably be solved in the future. From the surgical point of view, simple enuclea- tion is performed through an incision of the renal parenchyma at 12 mm from the neoplasia and through the blunt development of a space between the tumor pseudocapsule and the normal renal tissue, without any visible healthy parenchyma surrounding the tumor [1]. Starting from this assumption, how can we explain the presence of a 1-mm margin of kidney parenchyma around the pseudocapsule? Is it possible to think that the thickness of the healthy tissue surrounding the tumor is larger where the pseudocapsule is infil- trated by the tumor? Waiting for further studies confirming Minervini et als results [21], we believe it is only possible to formulate hypotheses. For example, the presence of chronic inflammation in the healthy tissue around the tumor could justify a stronger adhesion to the pseudocapsule, causing its involuntary removal during simple enucleation. This inflammation could be a direct consequence of the compression of the tumor on the healthy parenchyma or of a neoplastic infiltration of the pseudocapsule. To further inves- tigate this aspect, it could be useful to explore the correlations between the thickness of the tissue surrounding the neoplasia and the tumor size or the extension of the pseudocapsular infiltration. Even though the scientific attention is mostly focused on the parenchymal side of the tumor, the study by Minervini et al [21] highlights the impor- tance of the risk of infiltration also on the adipose slope of the tumor. Although less frequent than the parenchymal infiltration, from the oncologic point of view, the involvement of the perirenal fat has an Fig. 1 (a) Traditional partial nephrectomy with excision of an adequate additional margin of peritumor renal parenchyma (410 mm); (b) minimal partial nephrectomy with excision of a 1-mm safety margin. e ur op e an ur ol og y 5 5 ( 2 0 0 9 ) 1 3 1 5 1 3 2 0 1317 CASE STUDY What I did Lap Partial Clampless Enucleation (Selective microdissection) hemoloc on small vessels Hilar Vessels dissected with vessel loops around Bulldogs Near Temp 20mm Co2 5min EBL 100cc Time 65min thickness of 1 mm (range: 0.381.6) laying beyond the tumor pseudocapsule with signs of chronic inflammation [21]. This precious microscopic layer of renal parenchyma allows the presence of negative surgical margins also in patients with tumors extending beyond the pseudocapsule (Fig. 1). Taking into account the minimum thickness of the safety margin in the most recent NSS series, it is probable that in a significant percentage of cases the margin that resulted was 1 mm, substantially similar to the one reported by Minervini et al after simple enucleation [10,11,1316,21]. Therefore, sim- ple enucleation can be considered a safe technique, in perfect harmony with the EAU guidelines, which only recommend the presence of a minimal tumor- free surgical margin of healthy tissue in order to reduce the risk for local relapse [1]. Nevertheless, the study by Minervini et al raises new questions that will probably be solved in the future. From the surgical point of view, simple enuclea- tion is performed through an incision of the renal parenchyma at 12 mm from the neoplasia and through the blunt development of a space between the tumor pseudocapsule and the normal renal tissue, without any visible healthy parenchyma surrounding the tumor [1]. Starting from this assumption, how can we explain the presence of a 1-mm margin of kidney parenchyma around the pseudocapsule? Is it possible to think that the thickness of the healthy tissue surrounding the tumor is larger where the pseudocapsule is infil- trated by the tumor? Waiting for further studies confirming Minervini et als results [21], we believe it is only possible to formulate hypotheses. For example, the presence of chronic inflammation in the healthy tissue around the tumor could justify a stronger adhesion to the pseudocapsule, causing its involuntary removal during simple enucleation. This inflammation could be a direct consequence of the compression of the tumor on the healthy parenchyma or of a neoplastic infiltration of the pseudocapsule. To further inves- tigate this aspect, it could be useful to explore the correlations between the thickness of the tissue surrounding the neoplasia and the tumor size or the extension of the pseudocapsular infiltration. Even though the scientific attention is mostly focused on the parenchymal side of the tumor, the study by Minervini et al [21] highlights the impor- tance of the risk of infiltration also on the adipose slope of the tumor. Although less frequent than the parenchymal infiltration, from the oncologic point of view, the involvement of the perirenal fat has an Fig. 1 (a) Traditional partial nephrectomy with excision of an adequate additional margin of peritumor renal parenchyma (410 mm); (b) minimal partial nephrectomy with excision of a 1-mm safety margin. e ur op e an ur ol og y 5 5 ( 2 0 0 9 ) 1 3 1 5 1 3 2 0 1317