Laparoscopic Partial Nephrectomy versus Laparoscopic Cryoablation for Multiple Ipsilateral Renal Tumors

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1 european urology 53 (2008) available at journal homepage: Kidney Cancer Laparoscopic Partial Nephrectomy versus Laparoscopic Cryoablation for Multiple Ipsilateral Renal Tumors Yi-Chia Lin, Burak Turna, Rodrigo Frota, Monish Aron, Georges-Pascal Haber, Kazumi Kamoi, Philippe Koenig, Inderbir S. Gill * Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA Article info Article history: Accepted February 29, 2008 Published online ahead of print on March 18, 2008 Keywords: Cryoablation Kidney Laparoscopy Partial Nephrectomy Renal Tumor Abstract Background: Management of multiple ipsilateral renal tumors is a dilemma in clinical practice. The effects of minimally invasive nephron-sparing procedures in this group of patients have not been assessed. Objective: To evaluate the technical feasibility and outcomes of laparoscopic partial nephrectomy (LPN) and laparoscopic cryoablation (LCA) for multiple ipsilateral renal tumors. Design, Setting, and Participants: Between September 1999 and December 2006, 27 patients were treated with minimally invasive nephron sparing surgery (LPN or LCA) for synchronous multiple ipsilateral renal tumors in a single operating session at our institution. Fourteen patients with 28 tumors underwent LPN, and 13 patients with 31 tumors underwent LCA as the sole treatment modality. Intervention: Medical records were retrospectively reviewed and data were collected. Measurements: Demographic, intraoperative, postoperative, and intermediate-term follow-up data were compared between the two groups. Results and Limitations: Patients in the LPN group had fewer tumors (2 vs. 2.4, p = 0.04) and larger dominant tumor size (3.6 vs. 2.5 cm, p = 0.005) in the affected kidney and lower preoperative serum creatinine levels (1 vs. 1.4 mg/dl, p = 0.02). Compared to the LCA group, patients in the LPN group had greater estimated blood loss (200 vs. 125 ml, p = 0.02) and longer hospital stays (90 vs h, p= 0.02). There were no open conversions, and no kidneys were lost. Complication rate, renal functional outcomes, and intermediateterm cancer-specific survival rates were similar between the two groups. Conclusions: Both LPN and LCA are viable options for patients with multiple ipsilateral renal tumors in select patients. Renal functional outcomes, complication rates, and intermediate-term survival rates are comparable between the two groups in this small series. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic Foundation, A-100, Cleveland, Ohio 44195, USA. Tel ; Fax: addresses: burakturna@gmail.com (B. Turna), gilli@ccf.org (I.S. Gill) /$ see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 european urology 53 (2008) Introduction The aim of nephron-sparing procedures is oncologic control with maximum preservation of renal function. For small, localized, renal cell carcinoma (RCC) open partial nephrectomy (OPN) is the reference standard, because long-term survival and local recurrence rates are comparable to radical nephrectomy, with superior long-term preservation of renal function [1]. Over the past decade, minimally invasive nephron-sparing surgery (MINSS) has been increasingly employed for select patients who have small renal masses with promising oncologic and functional outcomes [2 5]. For multiple tumors in the ipsilateral kidney, radical nephrectomy is the reference standard. However, nephron-sparing surgery (NSS) is a viable option for select patients, especially those who have a solitary kidney, bilateral tumors, or chronic renal insufficiency. We have previously reported our experience of laparoscopic NSS in the setting of multiple tumors, with a special emphasis on the judicious adjunctive use of LCA or LPN [6]. However, to date, no study has compared the outcomes of single-modality LPN versus LCA for multiple ipsilateral renal tumors. Herein, we report our experience with LPN and LCA in patients with multiple ipsilateral renal tumors. 2. Methods Between September 1999 and December 2006, 14 patients underwent LPN and 13 patients underwent LCA for synchronous multiple ipsilateral renal tumors at our institution. These 27 patients with 59 tumors, identified from a prospectively maintained institutional review board approved database, formed the basis of the present study. Indication for NSS was imperative in 22 patients (81.5%): bilateral renal tumors (n = 13), solitary kidney (n = 3), chronic kidney disease (CKD) (n = 3), bilateral renal tumors and CKD (n = 2), and solitary kidney and CKD (n = 1). All patients underwent preoperative triphasic computed tomography (CT) scans with three-dimensional reconstruction for surgical planning. The criteria for treatment for each patient depended on the patient s age and associated co-morbidities, preoperative renal function, tumor size, number of tumors, the interrelationship of the ipsilateral tumors, and the surgeon s personal judgment. Our operative techniques for LPN and LCA have been described previously [2,3]. Intraoperative ultrasonography was performed in all patients to guide tumor ablation or excision. Postoperative follow-up consisted of serum creatinine measurement at 1 mo, and abdominal CT or magnetic resonance imaging (MRI) at 6 mo and yearly thereafter in patients with pathologically confirmed RCC. Local recurrence for LCA was defined as an enlarging or persistently enhancing treatment site on follow-up imaging; recurrence of tumor in the operated kidney was considered failure for LPN. Renal functional outcomes were evaluated with serum creatinine and estimated glomerular filtration rate (EGFR) using the Modification of Diet in Renal Disease (MDRD) equation [7]. If a patient could not be present for a followup appointment in the outpatient clinic, our dedicated research team conducted follow-up by telephone contact with the patient, family, or referring physician to obtain the information of recurrence and status of survival. Descriptive statistics are presented as median/range or frequency/proportion. Wilcoxon rank sum test was conducted for continuous variables, and chi-square test was used for categorical variables. Differences were considered to be statistically significant if p-value was less than Results Twenty-seven patients underwent either LPN (n = 14; 28 tumors) or LCA (n = 13; 31 tumors) for synchronous multiple ipsilateral renal tumors as the sole treatment modality in a single operating session (Table 1). All patients were available for Table 1 Demographic data LPN (n = 14) LCA (n = 13) p-value Age (yr) 58 (23 70) 69 (39 84) 0.01 Gender (M/F) 8:6 11:2 BMI 28.1 ( ) 25.9 ( ) 0.08 ASA score 3 (2 3) 3 (2 4) 0.5 Tumor laterality (R/L) 10:4 5:8 No. tumor per kidney 2 (2 2) 2.4 (2 3) 0.04 Dominant tumor size (cm) 3.6 ( ) 2.5 (1.5 3) Preop serum creatinine (mg/dl) 1.0 ( ) 1.4 ( ) 0.02 No. previous contralateral kidney surgery (%) 2 (14.2) 9 (69.2) No. solitary kidney (%) 1 (7.1) 3 (23.1) 0.24 No. bilateral tumor (%) 7 (50) 8 (61.5) 0.5 No. preop chronic kidney disease (%) 2 (14.2) 4 (30.8) 0.3 Data presented as median/range or frequency/proportion. BMI: body mass index, ASA: American Society of Anesthesiologists.

3 1212 european urology 53 (2008) follow-up in this series. Patients in the LPN group were younger (58 vs. 69 yr, p = 0.01). Median body mass index (BMI), American Society of Anesthesiologists (ASA) score, and tumor laterality were similar between the groups. Patients in the LPN group had fewer tumors (2 vs. 2.4, p = 0.04), larger dominant tumor size (3.6 vs. 2.5 cm, p = 0.005), and lower serum creatinine level (1 vs. 1.4, p = 0.02). Bilateral tumors were noted in seven patients in the LPN group (50%) and eight in the LCA group (61.5%). One patient in the LPN group (7.1%) and three patients in the LCA group (23.1%) had a solitary kidney. Preoperative CKD (serum creatinine > 1.5 mg/dl) was present in two patients (14.2%) in the LPN group and four patients (30.8%) in the LCA group. Imperative indication for NSS existed in 10 of 14 (71.4%) and 12 of 13 (92.3%) patients in the LPN and LCA groups, respectively. The remaining five patients underwent MINSS for multiple tumors because of intraoperative discovery of another tumor (n = 1), multiple comorbidities (n = 1), and surgeon preference/high index of suspicion for benign tumor (n = 3). History of prior contralateral renal surgery was present in two patients in the LPN group (radical nephrectomy [n = 1], embolization of angiomyolipoma [n = 1]) and nine patients in the LCA group (radical nephrectomy [n = 2], simple nephrectomy [n = 1], partial nephrectomy [n = 5], and LCA [n = 1]). Table 2 details the tumor characteristics in the LPN group. A total of 28 tumors were excised. Median warm ischemia time was 36 min (12 48) in 12 patients. Laparoscopic ice-slush renal hypothermia [8] was employed in two patients, with a median cold ischemia time of 40 min. Single LPN excision encompassing both tumors (en-bloc excision) was conducted in seven patients for tumors close to each other with a median warm ischemia time of 35 min (12 48). In the remaining seven patients, individual laparoscopic excision of discrete tumors located at a distance from each other was undertaken under cold ischemia in two patients (median cold ischemia time: 40 min) and under warm ischemia in five patients (median warm ischemia time: 41 [23 46] min). Patient 2 (Table 2) in the LPN group underwent clamped LPN for the larger tumor (diameter 3.4 cm) under cold ischemia and subsequent harmonic scalpel excision of the second tumor (diameter 1.2 cm) without hilar clamping. However, bleeding from the excision bed necessitated hilar re-clamping and subsequent suture repair under warm ischemia time of 3 min. In six of 14 patients, more than 30% of kidney parenchyma was excised (heminephrectomy). Median percentage of preserved renal parenchyma following LPN was 75% (60% to 95%). All 14 procedures were successfully completed without conversion to radical nephrectomy or open surgery. In all patients undergoing LPN, margins were negative for cancer, with a median margin thickness of 0.5 cm ( cm). Pathology confirmed RCC in 14 tumors (50%): five papillary, five clear cell, three chromophobe, and one cystic RCC. Histology in the remaining 14 tumors was angiomyolipoma (n = 7), oncocytoma (n = 4), malignant epithelioid tumor (n = 2), and fibrosis (n = 1). Table 3 provides the characteristics of the 31 tumors in the LCA group. Median cryo-time was 13.5 min (12 59 min) per lesion. Pre-ablation Table 2 Tumor characteristics in the LPN group No. tumors Location (aspect-pole) Indication Tumor size (cm) Warm ischemia time (min) Cold ischemia time (min) No. excision Histopathology 1 2 Hilum/Pos-Mid CKD 1.8/ RCC(papillary)/RCC(papillary) 2 2 Lat-Mid/Med-Low Solitary 3.4/ RCC(clear cell)/rcc(clear cell) 3 2 Med-Upp/Med-Upp Bilateral 2.9/ RCC(cystic)/RCC(clear cell) 4 2 Lat-Mid/Med-Low Elective 3.2/ RCC(chromophobe)/RCC(chromophobe) 5 2 Ant-Upp/Lat-Upp Elective 4.5/ AML/AML 6 2 Lat-Low/Ant-Low Bilateral 4.1/ RCC(chromophobe)/RCC(papillary) 7 2 Lat-Upp/Lat-low Bilateral 6.5/2.0 37/23 2 AML/AML 8 2 Lat-Mid/Lat-Mid Elective 7.7/ AML/fibrosis 9 2 Pos-Low/Lat-Low Bilateral 3.3/ RCC(papillary)/RCC(papillary) 10 2 Lat-Upp/Lat-Mid Bilateral 5.6/ Malignant epithelioid tumor/ Malignant epithelioid tumor 11 2 Lat-Low/Lat-Low CKD 1.5/ RCC(clear cell)/rcc(clear cell) 12 2 Ant-Mid/Lat-Mid Bilateral 10.3/ AML/AML 13 2 Pos-Mid/Pos-Low Bilateral 1.5/ Oncocytoma/oncocytoma 14 2 Lat-Low/Ant-Low Elective 3.7/ Oncocytoma/oncocytoma Lat: lateral, Med: medial, Ant: anterior, Pos: posterior, Upp: upper, Mid: middle, Low: lower, CKD: chronic kidney disease, RCC: renal cell carcinoma, AML: angiomyolipoma.

4 european urology 53 (2008) Table 3 Tumor characteristics in the LCA group No. tumors Location (aspect-pole) Indication Tumor size (cm) Cryo-time (min) No. probe Histopathology 1 2 Pos-Mid/Pos-Mid Solitary and CKD 2.8/2.3 15/11 1 Benign/RCC (clear cell) 2 2 Lat-Mid/Lat-Low CKD 1.5/1.4 23/12 2 Benign/inflammation 3 3 Ant-Upp/Pos-Mid/Med-Low Bilateral 2.2/2.0/0.9 21/20/15 3 RCC(clear cell)/rcc(clear cell)/benign 4 3 Lat-Mid/Lat-Low/Ant-Low Solitary 1.5/1.5/1.4 17/20/20 2 RCC(papillary)/RCC(papillary)/benign 5 2 Pos-Mid/Cen-Mid Bilateral 2.5/ /12 2 Benign/benign 6 3 Ant-Upp/Pos-Mid/Lat-Low Bilateral 2.5/2.0/1.2 17/19/12 1 Fibrosis/RCC(papillary)/RCC(papillary) 7 2 Ant-Low/Ant-Low Bilateral 2.3/1.6 17/ RCC(papillary)/RCC(papillary) 8 2 Ant-Mid/Lat-Mid Bilateral 2.5/1.4 10/15 2 RCC(papillary)/RCC(papillary) 9 2 Pos-Low/Pos-Low Bilateral 2.0/1.8 21/20 2 RCC(papillary)/benign 10 2 Pos-Mid/Lat-Upp Elective 3.0/2.1 17/15 2 Inflammation/RCC(clear cell) 11 3 Ant-Mid/Ant-Upp/Lat-Low Solitary 3.0/2.6/2.5 13/7 2 Oncocytoma/oncocytoma/Benign 12 3 Lat-Upp/Lat-Mid/Med-Low Bilateral & CKD 2.5/2.4/2.0 24/20/ Oncocytoma/oncocytoma/benign 13 2 Lat-Mid/Pos-Low Bilateral & CKD 2.0/1.8 16/13 1 RCC(clear cell)/rcc(clear cell) Lat: lateral, Med: medial, Ant: anterior, Pos: posterior, Cen: central, Upp: upper, Mid: middle, Low: lower, CKD: chronic kidney disease, RCC: renal cell carcinoma. Table 4 Comparison of perioperative outcomes (LPN versus LCA) LPN (n = 14) LCA (n = 13) p-value Approach (TP/RP) 13:1 6:7 EBL (ml) 200 (50 600) 125 (50 200) 0.02 OR time (min) 281 ( ) 240 (90 330) 0.17 No. blood transfusion (%) 1 (7.1) 0 (0) Hospital stay (hr) 90 (40 138) 52.3 (23 144) 0.02 No. complications (%) 3 (21.4) 4 (30.8) 0.68 DVT/PE (1) ileus (1) pneumonia (1) confusion (1) postop hemorrhage (1) retroperitoneal hematoma (1) urine leak (1) No. secondary surgical intervention None Ureteral stent (1) Data presented as median/range or frequency/proportion. TP: transperitoneal; RP: retroperitoneal; EBL: estimated blood loss; operating room (OR); DVT: deep vein thrombosis, PE: pulmonary embolism. core needle biopsy revealed RCC in 15 patients (papillary [n = 10], clear cell [n = 5]), benign parenchyma in nine patients, oncocytoma in four patients, and inflammation/fibrosis in three patients. Perioperative outcomes are summarized in Table 4. The LPN group had greater estimated blood loss (EBL) (200 vs. 125 ml, p = 0.02) and longer hospital stays (90 vs h, p = 0.02). Median operating room (OR) time and overall complication rate were comparable. Blood transfusion was required in one LPN and no LCA patients. The sole urine leak occurred in one patient in the LCA group 4 d after the procedure, requiring an ureteral stent. There was no mortality, open conversion, or lost kidneys. Renal functional outcomes are presented in Table 5. Preoperative serum creatinine level was lower in the LPN group (1 vs. 1.4 mg/dl, p = 0.02). However, there was no significant difference in postoperative percent change in serum creatinine. With regard to preoperative, postoperative, and percent change in EGFR, no significant change was noted between the two groups. In addition to the six preoperative CKD patients, post-operative CKD (serum creatinine > 1.5 mg/dl) occurred in three more patients in the LPN group and no patients in the LCA group. In this series, no patient required temporary or permanent dialysis even in patients Table 5 Renal functional outcomes after LPN and LCA LPN LCA p-value Serum creatinine (mg/dl) Preoperative 1.0 ( ) 1.4 ( ) 0.02 Postoperative 1.5 ( ) 1.4 ( ) 0.1 % increase 30 (0 70) 20 (0 90) 0.38 Estimated GFR * Preoperative 78.5 (45 133) 69 (23 114) 0.06 Postoperative 51.5 (42 110) 48 (17 83) 0.13 % decrease 23.5 (0 51.9) 26.1 (0 42.2) 0.27 Data presented as median/range. * Renal function evaluation included serum creatinine and estimated glomerular filtration rate (EGFR) using Modification of Diet in Renal Disease (MDRD) equation [7].

5 1214 european urology 53 (2008) with solitary kidneys and/or preexisting renal insufficiency. At a median follow-up of 38.5 mo (range 5 40) for the LPN and 24 mo (range 5 82) for the LCA group, there were no local recurrences. Distant metastasis occurred in one patient in the LCA group; that patient died 1 yr later. Overall and cancer-specific survival rates were 100% and 100% for the LPN group at 3 yr and 92% and 89% for the LCA group at 2 yr, respectively. 4. Discussion Multifocality of RCC is a concern in patients undergoing NSS for renal tumor. A retrospective study documented the incidence of multifocality to be 6% to 25% [9]. Whang et al, in a prospective study of radical nephrectomy patients, believed to be potential candidates for NSS, found a 25% incidence of multifocality [10]. Kletscher et al showed a 16% multifocality rate in radical nephrectomy specimens [11]. In our previous report on multiple tumors and laparoscopic NSS, we found a 4.5% multifocality rate [6]. Factors contributing to multifocality in sporadic, non-familial cases remain uncertain. Tumor stage [9,10], papillary or mixed histology [11], and intra-renal vascular invasion [12] are known to be associated with multifocality. In the present series, multifocality was seen in 3.7%. However, it is noteworthy that our patients constitute a highly select group in which the available pathology specimen is not the entire kidney; hence, this may not reflect the true incidence of multifocality. The reference standard for patients with multiple ipsilateral tumors is radical nephrectomy. However, optimal management of this cohort is debatable in the setting of an imperative indication for NSS. Contemporary evidence suggests that NSS can achieve oncologic outcomes comparable to those of radical nephrectomy for patients with multiple tumors. Blute et al [13] reported treatment of patients with multiple ipsilateral tumors containing at least one RCC; both radical nephrectomy and NSS provided similar cancer-specific survival. We consider NSS to be a viable treatment option for patients with multiple tumors in the setting of a solitary kidney, bilateral tumors, or CKD [6]. The safe limit of renal warm ischemia time has traditionally been considered 30 min. Preservation of renal function is crucial in patients with imperative indications. In our series, an imperative indication existed in 71% of patients treated with LPN and 92% of patients treated with LCA, respectively. Although warm ischemia time in the present series is longer compared to our entire series (36 vs. 32 min), postoperative renal function was preserved in all patients in the intermediate term (33 mo). Furthermore, the percent change in renal function (serum creatinine and EGFR) after the two procedures was comparable. Although no patient required dialysis in this series, three additional patients in the LPN group shifted toward the CKD category. Bhayani et al evaluated the effect of variable durations of warm ischemia on long-term renal function in 118 patients undergoing LPN [14]. The authors demonstrated that warm ischemia up to 55 min was not associated with significant deterioration of renal function. However, until more objective data are available, maximum effort should be made to keep warm ischemia time as short as possible. The LPN group showed significantly more EBL and longer hospital stays. However, there was no difference in terms of OR time, change in renal function, and overall complication rate. Also, both LPN and LCA were performed successfully without open conversion. Margins for cancer were negative in all patients receiving LPN. Intermediate-term (33 mo) oncologic outcomes were also favorable, and comparable between the two groups. Five patients in this series underwent MINSS (LPN [n = 4], LCA [n = 1]) for elective indications. One patient underwent LPN for preoperative diagnosis of a single tumor; a second, smaller tumor was incidentally discovered during intraoperative ultrasonography. Three other patients in the LPN group underwent elective LPN: in two patients, there was a high index of suspicion for benign mass on preoperative CT scan, and in one patient, the tumors were so close that en-bloc excision of adjacent tumors was considered feasible. The sole elective LCA was performed in the setting of multiple comorbidities (diabetes, hypertension, and abdominal aortic aneurysm) and borderline elevation of serum creatinine. In these patients, no recurrence or postoperative renal functional impairment was noted. We have previously reported feasibility of MINSS for multiple tumors as well as excellent 5-yr outcomes after single-tumor LPN and LCA [6,15 17]. Given the tremendous experience of the senior author, it is reasonable to expect that the complication rate may be somewhat higher in the hands of less-experienced surgeons, especially for LPN, which is technically more challenging than LCA. Until the global dissemination of minimally invasive techniques occurs, the management of such

6 european urology 53 (2008) complex cases should be undertaken by centers of excellence through computer-based networks and collaborations between the centers of excellence and the urological community. There is still a strong need for increased advanced laparoscopic training for urologists, which can be accomplished by expanding training facilities (dry lab and wet lab), increasing the number of preceptorship programs (local and international), increasing the number of minimally invasive surgery educational courses (including hands-on training), local endourologic societies taking more action (inviting experts in laparoscopy), and urologic journals including more surgery-related publications (eg, Surgery in Motion). Cost considerations are increasingly playing a major role in how physicians treat their patients. Mouraviev et al reported a comparative financial analysis of minimally invasive surgery (handassisted laparoscopic nephrectomy, LPN, and LCA) versus open surgery in 184 patients with small renal tumors [18]. The authors found that the costs of minimally invasive surgery were competitive with traditional open surgery. Because of unresolved critiques of renal probeablation namely, leaving the tumor in situ, lack of long-term oncologic data, and lack of histologic confirmation of complete tumor destruction our personal preference is still to employ LPN for the larger tumor, when tumors are widely separated from each other. In the setting of tumors that are widely separated, where the second, smaller tumor is very exophytic, we would perform clamped LPN for the larger tumor and unclamped LPN for the smaller, exophytic tumor. Currently, we cryoablate a lesion if the patient has advanced CKD, if a second LPN would unduly prolong warm ischemia, or if the location of the tumor is such that considerable renal parenchyma would need to be sacrificed for safe excision. As expected, we prefer en-bloc LPN for tumors that are close to each other. We have modified our LPN technique so that our warm ischemia time is consistently less than 15mininthemajorityofcases[19]. Weadvocate the use of a hybrid technique in select patients, where a judicious combination of LPN and LCA is employed in the individual patient to maximize oncologic and renal functional outcomes. Finally, a patient whose solitary kidney harbors multiple tumors in difficult locations would still remain a candidate for highly specialized OPN. As such, the treatment plan should be tailored to the individual patient depending on patient, renal, and tumor characteristics. The limitations of this report are inherent to the retrospective nature of the data analysis and relatively small numbers in each group. The limited power of our analysis may not be large enough to detect clinically significant differences between LPN and LCA for some of the outcomes. Therefore, one must be careful in interpreting our results. Also, the median age, dominant tumor size, and preoperative creatinine levels were different in the two groups, and these factors may cause selection bias. However, data were prospectively collected, follow-up duration was reasonable, and patient numbers were comparable in both groups. 5. Conclusions Given adequate experience, LPN is an acceptable treatment option for patients with multiple ipsilateral renal tumors. LCA is emerging as an effective and safe treatment alternative in select patients. Renal functional outcomes, complication rates, and intermediate-term survival rates are comparable between the two groups in this small series. However, LPN is associated with higher EBL and longer hospital stays. The treatment plan should be tailored to surgeon expertise as well as individual patient and tumor characteristics. Finally, an evaluation and comparison between the percutaneous and laparoscopic probe-ablative treatments would be of value. Author contributions: Inderbir S. Gill 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: Lin, Turna, Haber, Gill. Acquisition of data: Lin, Koenig, Frota. Analysis and interpretation of data: Lin, Turna, Frota, Koenig, Kamoi. Drafting of the manuscript: Lin, Turna, Frota, Aron. Critical revision of the manuscript for important intellectual content: Lin, Turna, Aron, Haber, Gill. Statistical analysis: Lin, Koenig, Kamoi. Obtaining funding: none. Administrative, technical, or material support: none. Supervision: Gill. Other (specify): none. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none. Funding/Support and role of the sponsor: none.

7 1216 european urology 53 (2008) References [1] Fergany AF, Hafez KS, Novick AC. Long-term results of nephron sparing surgery for localized renal cell carcinoma: 10-year followup. J Urol 2000;163: [2] Aron M, Gill IS. Minimally invasive nephron-sparing surgery (MINSS) for renal tumours. Part I: laparoscopic partial nephrectomy. Eur Urol 2007;51: [3] Aron M, Gill IS. Minimally invasive nephron-sparing surgery (MINSS) for renal tumours. Part II: probe ablative therapy. Eur Urol 2007;51: [4] Mouraviev V, Joniau S, Van Poppel H, Polascik TJ. Current status of minimally invasive ablative techniques in the treatment of small renal tumours. Eur Urol 2007;51: [5] Wyler SF, Sulser T, Ruszat R, et al. Intermediate-term results of retroperitoneoscopy-assisted cryotherapy for small renal tumours using multiple ultrathin cryoprobes. Eur Urol 2007;51: [6] Steinberg AP, Kilciler M, Abreu SC, et al. Laparoscopic nephron-sparing surgery for two or more ipsilateral renal tumors. Urology 2004;64: [7] Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130: [8] Gill IS, Abreu SC, Desai MM, et al. Laparoscopic ice slush renal hypothermia for partial nephrectomy: the initial experience. J Urol 2003;170:52 6. [9] Baltaci S, Orhan D, Soyupek S, Beduk Y, Tulunay O, Gogus O. Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma. J Urol 2000;164: [10] Whang M, O Toole K, Bixon R, et al. The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. J Urol 1995;154: [11] Kletscher BA, Qian J, Bostwick DG, Andrews PE, Zincke H. Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy. J Urol 1995;153: [12] Gohji K, Hara I, Gotoh A, et al. Multifocal renal cell carcinoma in Japanese patients with tumors with maximal diameters of 50 mm. or less. J Urol 1998;159: [13] Blute ML, Thibault GP, Leibovich BC, Cheville JC, Lohse CM, Zincke H. Multiple ipsilateral renal tumors discovered at planned nephron sparing surgery: importance of tumor histology and risk of metachronous recurrence. J Urol 2003;170: [14] Bhayani SB, Rha KH, Pinto PA, et al. Laparoscopic partial nephrectomy: effect of warm ischemia on serum creatinine. J Urol 2004;172: [15] Lane BR, Gill IS. 5-Year outcomes of laparoscopic partial nephrectomy. J Urol 2007;177:70 4. [16] Desai MM, Aron M, Gill IS. Laparoscopic partial nephrectomy versus laparoscopic cryoablation for the small renal tumor. Urology 2005;66:23 8. [17] Hegarty NJ, Gill IS, Desai MM, Remer EM, O Malley CM, Kaouk JH. Probe-ablative nephron-sparing surgery: cryoablation versus radiofrequency ablation. Urology 2006;68: [18] Mouraviev V, Nosnik I, Robertson C, Albala D, Walther P, Polascik TJ. Comparative financial analysis of minimally invasive surgery to open surgery for small renal tumours 3.5 cm: a single institutional experience. Eur Urol 2007;51: [19] Nguyen MM, Gill IS. Halving the ischemia time during laparoscopic partial nephrectomy. J Urol 2008;179: Editorial Comment on: Laparoscopic Partial Nephrectomy Versus Laparoscopic Cryoablation for Multiple Ipsilateral Renal Tumors Didier Jacqmin IRO EAU d.jacqmin@uroweb.org Lin et al [1] address the best management of multiple ipsilateral tumors in kidney cancer, which a rare situation to find in standard practice. They ask, is laparoscopic partial nephrectomy better than laparoscopic cryoablation? Their methodology raises some questions. Because of the rare occurrence of such a situation, the number of patients (27) is limited. Two groups of 14 versus 13 are presented. The two groups, as expected, are not equivalent in numbers of tumors, size, location, creatinin level, blood loss, hospital stay, and so forth. This study is monocenter, nonprospective, and nonrandomized. Finally, these two options are neither considered to be validated nor recommended in guidelines. The study presents preliminary results with maybe a level 4 of evidence. It also raises questions about the validity of proposed therapeutic options described in many papers in the urologic literature. Laparoscopic partial nephrectomy is not yet validated. Even in expert hands, it seems that the technique still induces higher morbidity and positive margin rates than open surgery [2]. No comparable prospective study is currently available. Even open partial nephrectomy, usually considered as a standard treatment, has not been fully evaluated prospectively despite the efforts of the European Organization for Research and Treatment of Cancer (EORTC) and of Hein Van

8 european urology 53 (2008) Poppel. The only prospective trial had to be stopped because of poor recruitment related to the arrival of laparoscopic surgery [3]. This comment is not directed against the authors of this paper, who have raised interesting questions. The real problems are more general: (1) we have to improve the methodologies of the papers we propose to urological journals; (2) it is the role of journals to push us in that direction; and (3) if we do not improve our work, others specialties such as oncology or radiotherapy will continue to have reason to criticize urologists, our papers, and our journals. Urologists all around the world should be more scientific; should define methodologies for the evaluation of surgical studies; should define criteria to express toxicity (mortality and morbidity) of surgical procedures as it is available for chemotherapy; and should define criteria to confirm, as fast as possible, the efficacy of novel procedures. It is impressive to see the small number of evidence level 1 or 2 in the guidelines for surgical aspects of urology. We have to wake up as fast as possible and realize that we are living in the 21st century. If we don t do it ourselves, others specialties will do it for us, if not patient organizations or health care authorities. References [1] Lin Y-C, Turna B, Frota R, et al. Laparoscopic partial nephrectomy versus laparoscopic cryoablation for multiple ipsilateral renal tumors. Eur Urol 2008;53: [2] Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007;178:41 6. [3] Van Poppel H, Da Pozzo L, Albrecht W, et al. A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2007;51: DOI: /j.eururo DOI of original article: /j.eururo Editorial Comment on: Laparoscopic Partial Nephrectomy versus Laparoscopic Cryoablation for Multiple Ipsilateral Renal Tumors David C. Miller Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA dcmiller@mednet.ucla.edu This paper is important because it depicts the frontier for applying minimally invasive, nephron-sparing therapies in patients with renal cortical neoplasms [1]. Although many patients faced with the complex dilemma of multiple tumors in the same kidney undergo radical nephrectomy, a growing body of evidence supports the long-term benefits of renal function preservation and motivates use of nephron-sparing surgery whenever oncologically prudent and technically feasible [2]. Accordingly, the authors ability to provide this complex group of patients with not only a nephron-sparing therapy, but also the easier convalescence of a minimally invasive approach serves as a technical benchmark for the larger urologic community. Nonetheless, widespread clinical implementation of the findings from this paper is likely to require concerted efforts to dismantle residual barriers to surgeons adoption of partial nephrectomy and laparoscopy, whose dissemination has been protracted and inconsistent [3,4]. The solution to this challenge may ultimately involve some combination of educational programming, policy-based interventions (eg, selective referrals), and sustained collaboration among urologists in surgical practice-based research networks [5]. References [1] Lin Y-C, Turna B, Frota R, et al. Laparoscopic partial nephrectomy versus laparoscopic cryoablation for multiple ipsilateral renal tumors. Eur Urol 2008;53: [2] Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol 2006;7: [3] Miller DC, Taub DA, Dunn RL, Wei JT, Hollenbeck BK. Laparoscopy for renal cell carcinoma: diffusion versus regionalization? J Urol 2006;176:

9 1218 european urology 53 (2008) [4] Miller DC, Hollingsworth JM, Hafez KS, Daignault S, Hollenbeck BK. Partial nephrectomy for small renal masses: an emerging quality of care concern? J Urol 2006;175:853 7, discussion 858. [5] Corica FA, Boker JR, Chou DS, et al. Short-term impact of a laparoscopic mini-residency experience on postgraduate urologists practice patterns. J Am Coll Surg 2007;203: DOI: /j.eururo DOI of original article: /j.eururo