Articles

Positive Surgical Margins After Nephron-Sparing Surgery

By: Martin Marszaleka b lowast , Marco Carinic, Piotr Chlostad, Klaus Jeschkee, Ziya Kirkalif, Ruth Knüchelg, Stephan Madersbachera, Jean-Jacques Patardh and Hendrik Van Poppeli

Published online: 01 April 2012

Keywords: Margin, Partial nephrectomy, Nephron-sparing surgery, Frozen section, Recurrence

Abstract Full Text Full Text PDF (168 KB)

Abstract

Context

Little is known on the natural history of positive surgical margins (PSMs) in partial nephrectomy (PN). Accumulating data suggest that secondary nephrectomy might not be necessary in all patients with PSMs after PN.

Objective

Provide an overview on incidence and risk factors for PSMs after partial nephrectomy and on the rate of local and distant disease recurrence related to PSMs. We also provide recommendations on how to avoid and how to treat PSMs after PN.

Evidence acquisition

A nonsystematic literature research was based on Medline, Scopus, and Web of Science queries on these keywords: nephron-sparing surgery, partial nephrectomy/ies, and margin. Only human studies (original research) published in English were included.

Evidence synthesis

PSMs are present in 0–7% of patients after open PN, in 0.7–4% after laparoscopic PN, and in 3.9–5.7% after robot-assisted PN. The thickness of healthy parenchyma surrounding the tumour is irrelevant as long as complete tumour removal is achieved. The coincidence of a highly malignant tumour and PSM increases the risk of local recurrence. Intermediate follow-up data indicate that the vast majority of patients with PSMs will not experience local or distant tumour recurrence. Frozen-section analysis for evaluation of resection margins during PN is of minor clinical significance, as the surgeon's gross assessment of macroscopically negative margins provides reliable results.

Conclusions

PSMs in PN are rare. As indicated by intermediate follow-up data, the majority of patients with PSMs after PN remain without disease recurrence, and a surveillance strategy seems preferable to surgical reintervention.

Take Home Message

Positive surgical margins (PSMs) in partial nephrectomy occur in 0–7% of cases, regardless of the surgical technique applied. The majority of patients with PSMs will not experience disease recurrence at intermediate follow-up. Therefore, a surveillance strategy seems preferable to surgical reintervention in such patients.

Keywords: Margin, Partial nephrectomy, Nephron-sparing surgery, Frozen section, Recurrence.

1. Introduction

A lower risk of chronic kidney disease (CKD), as expected from nephron-sparing surgery, reduces the risk of cardiovascular events and directly translates into improved overall survival [1], [2], and [3]. The risk of incomplete tumour removal, however, is of concern with PN. Little is known of the natural history of positive surgical margins (PSMs) in kidney cancer surgery, although it seems that the majority of these patients neither progress locally nor experience distant metastasis [4]. Although complete tumour removal is an oncologic principle of paramount importance, accumulating data suggest that secondary nephrectomy might not be the treatment of choice in all patients with PSMs after PN. However, it is unclear how to define the patient at risk for a PSM and for disease recurrence after PSM and if the incidence of PSM is related to the surgical approach or technique (eg, open vs laparoscopic vs robot-assisted PN, simple tumour enucleation).

This review provides a comprehensive overview of incidence and significance of PSMs after nephron-sparing surgery for renal tumours. We outline information on the risk factors for PSMs and highlight the rate of local and distant disease recurrence related to a PSM. Finally, this review provides recommendations on how to avoid and how to treat PSMs after nephron-sparing surgery.

2. Evidence acquisition

A comprehensive nonsystematic literature research was based on free-text queries on Medline, Scopus, and Web of Science on the combination of the keywords nephron sparing surgery, partial nephrectomy/ies, and margin from 1 January 2001 to 10 July 2011. Only human studies (original research) published in English were included. Reference lists in the respective articles were surveyed for related literature. Review articles were screened for missing articles but excluded from the final reference list, as were meeting abstracts and articles on paediatric surgery. Because of the absence of randomised trials and the low prevalence of PSMs, weighted cumulative analysis and comparative analyses were not performed.

3. Evidence synthesis

Articles including larger cohorts of patients with PSMs after PN are scarce. Therefore, conclusions were mainly based on small series of patients with limited follow-up. As not a single randomised controlled trial is available, the included studies (n=69) are case series and nonrandomised comparisons with level ≤3 evidence.

3.1. Incidence and risk of positive surgical margins after partial nephrectomy

A PSM after PN is a rare event. In the current literature, overall rates of PSMs range from 0% to 7% [4], [5], [6], [7], [8], and [9]. According to the surgical approach, PSM rates are 0–7% after open PN (OPN), 0.7–4% after laparoscopic PN (LPN), and 3.9–5.7% after robot-assisted PN (RAPN) (Table 1). Few authors have reported PSM rates as high as 18% in selected patient cohorts containing larger tumours or undergoing PN for imperative indications (Table 2).

Table 1 Studies reporting positive surgical margin rates after partial nephrectomy

Study Patient s, no. Surgical technique Tumor size, cm PSM rate, % Comment
Patard et al. [6] 1048 OPN 3.4 1.5 (<4 cm) 1.3 (>4 cm) Similar PSM rates in tumours <4cm and >4 cm
Kwon et al. [7] 777 OPN 2.6 7 Higher local recurrence rate in highly malignant tumours and PSM
Saranchuk et al. [10] 54 OPN 3.4 15 Solitary kidneys
Zigeuner et al. [12] 117 OPN 3.4 5 PSM do not reliably predict residual tumour tissue
Van Poppel et al. [14] 268 OPN 5.1 Tumor size <5cm in 98.9%
Bernhard et al. [55] 809 OPN 3.4 1.5 PSM are independent risk factor for ipsilateral tumor recurrence (8.1% LPN included)
Duvdevani et al. [57] 301 OPN 3.6/3.2* 0.6/4.2* No vascular occlusion may increase risk of PSM
Duvdevani et al. [64] 301 OPN 3.6 2 Accuracy of frozen-section analysis is questionable
Lifshitz et al. [9] 184 LPN 2.5 3 PSM rate similar in first and last 50 patients of surgeon experience
Porpiglia et al. [18] 90 LPN 3.1 4.4 Higher PSM rate in patients with complications
Permpongkosol et al. [19] 511 LPN 2.8 1.8 PSM does not necessarily indicate residual disease
Link et al. [25] 223 LPN 2.6 3.5 PSM rate comparable to open series of PN
Porpiglia et al. [44] 100 LPN 2.4 (<4 cm) 5 (<4 cm) 3.9 (<4 cm) 0.3 (>4 cm) Comparable PSM rates in tumours <4cm and >4 cm
Breda et al. [46] 855 LPN 2.7 2.5 Discrepancy between frozen-section and final pathology
Frank et al. [47] 363 LPN 3.0 (central tumor) 2.4 (peripheral tumor) 0.8 (central tumor) 0.7 (peripheral tumor) PSM status similar in central and peripheral tumors
Venkatesh et al. [49] 123 LPN 2.6 2.5 PSM rate during initial surgeon experience
Scoll et al. [13] 100 RAPN 2.8 5.7
Rogers et al. [21] 148 RAPN 2.8 4
Mottrie et al. [22] 62 RAPN 2.8 2
Gill et al. [5] 200 LPN 2.8 3.0
OPN 3.3 0.0
Gill et al. [15] 1800 LPN 2.6 2.9 PSM rate for cancer: 1.6 (OPN), 1.0% (LPN)
OPN 3.3 1.3
Marszalek et al. [16] 200 LPN 2.8 4 Similar rates of PSM in matched-pair comparison of LPN and OPN
OPN 2.9 2
Gong et al. [17] 153 LPN 2.9 1.3 PSM rate comparable in LPN and OPN
OPN 2.5 1.3
Benway et al. [26] 247 LPN 2.5 1.0 A learning curve exists for RAPN with regard to margin status
RAPN 2.8 3.9
Yossepowitch et al. [4] 1390 NA 3.5 5.5 Select patients with a PSM can be offered vigilant monitoring

PSM=positive surgical margin; PN=partial nephrectomy; NA=not applicable; RAPN=robot-assisted laparoscopic nephrectomy; LPN=laparoscopic partial nephrectomy; OPN=open partial nephrectomy.

Table 2 Studies reporting positive surgical margins in patients undergoing partial nephrectomy in an imperative indication

Study Patients with imperative indication, no. Patients with PSM, no. Follow-up, mo Tumor size, cm Patients with local recurrence, no. Patients with distant metastasis, no.
Saranchuk et al. [10] 54 8 40.5 3.4 2 3
Peycelon et al. [11] 40 11 70.7 5.6 1 2
Lee at al [42] 30 5 29.0 3.3 2 NA
Wszolek [43] 101 9 56.0/59.0* 3.6/4.1* NA NA

* Nonclamping/clamping group.

PSM=positive surgical margin; NA=not applicable.

3.2. Surgical technique

3.2.1. Does the surgical approach have any influence on the occurrence of positive surgical margins?

PN is performed by open, laparoscopic, and, in recent series, robot-assisted surgery. Several studies have shown the oncologic efficacy of OPN with regard to surgical margin (SM) status [4], [5], [12], [13], and [14]. In recent years, LPN, either by the trans- or retroperitoneal approach, became increasingly available. Although LPN reduces the morbidity of the procedure and allows for quicker reconvalescence, the demanding technical complexity of LPN requires an experienced laparoscopic surgeon. Few comparative studies provide data on OPN and LPN with regard to SM status (Table 1); no randomised trials are available. The largest multi-institutional study by far, performed by Gill et al, revealed comparable PSM rates of 1.3% and 2.8% in OPN and LPN [15]. Similar results were reported by others [16], [17], [18], [19], and [20]. As an evolution of the laparoscopic technique, RAPN is gaining acceptance. Improved visualisation of the surgical field and the advantage of fully articulating instruments seem to eclipse the adherent economic burden. PSM rates after RAPN are within the range of OPN and LPN [13], [21], [22], [23], and [24].

The impact of the learning curve on PSM rate is difficult to assess; more demanding tumours will be approached with increasing experience. An impact of the learning curve of PN on PSM rate cannot be derived from initial institutional results [9], [13], [25], and [26].

3.2.2. Thickness of healthy parenchyma surrounding the tumour/tumour enucleation

Historically, a 1-cm rim of regular renal tissue was recommended to ensure complete tumour removal [27]. Meanwhile, accumulating data underscore that a minimum of regular renal parenchyma covering the tumour provides the oncologic safety required for PN without an additional risk of complications and the unnecessary loss of healthy tissue [28] and [29]. Furthermore, margin status is the most important end point [28], [29], [30], [31], [32], [33], [34], [35], and [36]; safety margin thickness does not correlate with disease progression [29]. The 2011 edition of the European Association of Urology guidelines on the treatment of localised renal cell cancer (RCC) also considers a minimal tumour-free margin sufficient to avoid local tumour recurrence [37].

Simple tumour enucleation yielded oncologic results comparable to PN [36], [38], [39], and [40], although a prospective randomised trial comparing PN and simple enucleation of renal masses has not been conducted. During tumour enucleation, a natural cleavage plane between the tumour pseudocapsule and regular kidney parenchyma allows for blunt dissection without entering the tumour [36]. Even in the case of neoplastic pseudocapsule invasion, a thin layer of chronic inflammatory tissue may still prevent a PSM [36]. However, a pseudocapsule serving as landmark for simple enucleation will be missing in some tumours [34]. These patients are exposed to the risk of a PSM by an attempted tumour enucleation. The largest retrospective study to date on enucleation of renal masses was conducted by Minervini et al. [41] and compared 537 patients after tumour enucleation to 982 patients after standard PN at a median follow-up of 54.4 mo. The 10-yr cancer-specific survival was similar in both groups, but the PSM rate was higher after PN (3.4% vs 0.2%) [41]. Multi-institutional long-term follow-up data are awaited to confirm these results.

3.2.3. Influence of imperative versus elective indication

Patients with an imperative indication for PN present often with larger tumours, unfavourable tumour localisation, and tumours that otherwise would have undergone radical nephrectomy. Therefore, a higher incidence of PSM is observed in imperative indications (Table 2). In a series of 54 patients with solitary kidneys undergoing OPN for renal masses, Saranchuk et al. reported a PSM rate of 15% [10].

3.2.4. Positive surgical margins and tumour size

The correlation of tumour size and PSM rate is still subject to debate. Patard and others found comparable PSM rates in tumours smaller and larger than 4cm [6] and [44]. However, higher PSM rates with decreasing tumour size were also observed [4] and [45]. Small tumour size might prevent the surgeon from accurately estimating tumour extension and thereby provoke a PSM. A missing or incompletely developed pseudocapsule, particularly present in smaller tumours, may also contribute to higher PSM rates. Finally, accidental disintegration of the resection margin is more likely to occur in smaller tumours.

3.2.5. Positive surgical margins and tumour localisation

Studies on the relationship of PSM and tumour localisation are rare [46], [47], [48], and [49]. PSM rates for central and peripheral tumours are either comparable [47] or higher in central tumours [48] and [49]. In a retrospective multicentre analysis, Bensalah et al. compared 111 patients with PSMs to 664 patients with negative SM (NSM). Centrally located tumours were present in 29% of patients with PSMs but in only 9.1% of those with NSM [48]. None of the studies available applied reproducible nephrometry scores [50] and [51], a useful tool that will improve comparability of future studies. Therefore, conclusions that can be drawn are limited by the arbitrary definition of tumour localisation. After all, the complexity of PN seems to translate into SM status, as small and endophytic tumours may be more demanding of the surgeon's skills than larger exophytic ones.

3.3. Impact of histologic subtype

Only two studies present data on the relation of PSM and tumour histology. In their analysis of 777 OPN, Kwon et al. found comparable PSM rates in tumours with low (oncocytoma, angiomyolipoma, papillary RCC type I, chromophobe RCC, and other benign lesions) and high malignant potential (clear cell RCC, collecting-duct carcinoma, papillary RCC type II, and tumours with sarcomatoid differentiation) based on the Heidelberg classification of histologic subtypes [7]. Tumour histology was not predictive of SM status. In patients with PSMs, local or distant disease recurrence (n=4) was only observed in those with highly malignant tumours. No patient with a tumour of low malignant potential showed local recurrence. The authors concluded that patients with highly malignant tumours and PSMs are at higher risk of local recurrence. Others observed higher proportions of high-grade tumours in patients with PSMs [48]. This could be related to tumour morphology, for example, infiltrative growth and not well delineated tumours. Finally, an impact of tumour morphology on PSM rate cannot be excluded.

3.4. Positive surgical margins, tumour recurrence, and survival

The results of nephron-sparing surgery for small RCC are excellent; however, the risk of disease recurrence, although minimal, is of concern. Whether or not a PSM is a risk factor for disease recurrence after PN has been controversial, but results are comparable in most series: PSMs increase the risk of disease recurrence, but influence on survival is limited [11] and [16] (Table 3). One of the largest studies on patients with PSMs after PN did not observe an increased risk of local recurrence or metastatic progression (median follow-up: 3.4 yr) [4]. The only predictor of local and distant disease recurrence was tumour size. Also at longer follow-up (80.5 mo), patients with PSMs did not experience any recurrences [53]. However, other investigators reported higher recurrence rates with PSMs [19], [48], and [55]. A recent analysis of 809 PN identified PSM as an independent risk factor for ipsilateral tumour recurrence [55]. The PSM rate in this analysis was 1.5%. One-third of those patients developed local recurrence (median time to detection: 23.2 mo). Another survey of 775 patients after PN also observed an increased risk of and a shorter time to disease recurrence with PSM [48]. However, cancer-specific and overall survival were not affected by margin status (mean follow-up: 37 mo). The combination of highly malignant tumours and PSMs may also increase the risk of local recurrence [7]. In summary, PSMs after PN harbour an increased risk of disease recurrence, especially in patients with tumours of high malignant potential. The vast majority of patients with PSMs do not experience local or distant tumour recurrence, but only intermediate follow-up data are available. Given a vigilant monitoring protocol, surveillance seems to be a viable alternative to salvage surgery in those patients, thereby preventing overtreatment and further renal function loss.

Table 3 Studies reporting recurrence data related to positive surgical margins

Study Follow-up, mo Patients with PSM, no. Patients with local recurrence, no. Patients with distant metastasis, no. Patients with NED, no. Comment
Yossepowitch et al. [4] 39.6 77 NA NA NA PSM not associated with increased risk of local recurrence or metastatic disease
Kwon et al. [7] 22 57 2 2 53 Higher local recurrence rate in highly malignant tumours with PSM
Lifshitz et al. [9] 18 6 0 0 6 PSM rate in initial and advanced experience
Zigeuner et al. [12] 76/85* 6 2 3 3 PSM are frequently caused artificially
Scoll et al. [13] 12.7 5 0 0 5 Patients after RAPN
Gill et al. [15] 22.8 21 1 1 20 Results of 1800 patients undergoing LPN/OPN
Permpongkosol et al. [19] 32 7 0 1 6 PSM do not necessarily indicate residual disease
Benway et al. [21] 26 7 0 0 7 Patients after RAPN
Benway et al. [26] 48/12 1/5 0 0 6 LPN/RAPN
Piper et al. [32] 60 7 0 2 5 Questions the necessity of 1-cm margin width
Minervini et al. [41] >51 26 1 NA NA Patients after standard PN and simple enucleation
Raz et al. [45] 40 4 0 0 4 Avoid nephrectomy as response to PSM
Bensalah et al. [48] 37 111 7 4 NA PSM occur more frequently in imperative cases. PSM associated with increased risk of recurrence, but do not affect CSS
Desai et at [52] 56.4 5 0 0 5 Surveillance in selected patients may be adequate without sacrificing oncologic control
Lopez-Costea et al. [53] 80.5 9 0 0 9 Manage microscopic PSM conservatively
Ray et al. [54] 24.0 8 0 0 8 OPN
Duvdevani et al. [64] 53.4 4 1 0 3 Accuracy of frozen sections in PN questionable

* Elective versus imperative indication group.

PSM=positive surgical margin; NED=no evidence of disease; NA=not applicable; RAPN=robot-assisted laparoscopic nephrectomy; LPN=laparoscopic partial nephrectomy; OPN = open partial nephrectomy; CSS=cancer-specific survival.

3.5. How to avoid a positive surgical margin

Several circumstances might pave the way for the occurrence of a PSM, such as impaired intraoperative visibility, poor orientation, and rather small but deeply infiltrating tumours. Small, entirely exophytic tumours may be safely resected without hilar clamping, although some authors underline the role of temporary vascular occlusion to improve visualisation of the resection margin [22], [56], and [57]. However, no difference in PSM rate was observed in a recent analysis comparing PN with and without hilar clamping [58]. Another method to achieve NSM is ultrasound-guided placement of a curved needle around the intraparenchymal portion of the tumour [59], helping the laparoscopic surgeon remain in the resection plane. However, PSMs may still occur laterally to the needle's plane, limiting the clinical benefit of this method.

Endophytic growth pattern or adherent perinephric fat may obviate tumour localisation. In such cases, intraoperative ultrasound and, recently, near-infrared fluorescence imaging can be valuable in correctly defining tumour extent, intended resection line, and renal vasculature [60] and [61]. Augmented reality navigation systems are able to superimpose virtually created and real-time images, thereby facilitating laparoscopy port placement and identification of tumour and adjacent structures [62]. Such auxiliaries may potentially increase the precision of PN in the future, although their impact on PSM rates remains to be determined.

3.6. Frozen section analysis: useful or useless?

Methods for intraoperative evaluation of SMs are routine frozen-section analysis, on-site pathologic examination, gross inspection of the resection margin by the surgeon, and on-demand frozen section in ambiguous cases. The accuracy of frozen-section analysis, in particular, met with criticism due to intermittent false-negative or inconclusive results that did not correlate well with final pathology [12], [32], [38], [63], [64], and [65]. Accurate diagnosis is also hampered by insufficient minute fragments of tissue sent to the pathologist for frozen-section analysis [66]. Tumour-bed biopsies represent only a small fraction of the resection margin and, in general, deliver unreliable results. In select cases, frozen-section analysis of suspicious areas of the resected specimen may improve diagnostic accuracy [67]. A robust accordance exists between gross SM interpretation by the surgeon and final histologic analysis [68]. The surgeon's gross interpretations provide reliable results sufficient for intraoperative decision making and particularly for avoiding false-negative results. Furthermore, with LPN and RAPN, tumour extraction is usually the final step after renal repair, which obviates the time-consuming process of frozen-section analysis. Finally, an additional safety margin created by intensive fulguration of the resection bed by cautery or argon beam may render PSMs clinically insignificant. Against this background, routine frozen-section analysis delivers no additional information of clinical significance.

3.7. Management of positive surgical margins

Disease recurrence rate after PSMs is low and impact on survival is limited. When counselling patients with PSMs, all therapeutic options—radical nephrectomy, repeat PN, energy ablation, and observation—should be taken into consideration. Radical nephrectomy may adequately address a PSM from an oncologic point of view, but the nephrectomy specimen after PN will only contain tumour remnants in 6.9% to 15% of cases [45] and [69]. In addition, radical nephrectomy will sacrifice well functioning renal tissue, thus elevating the risk of CKD, which, in turn, leads to decreased survival [2] and [3]. For these reasons, radical nephrectomy after PN with PSM is not the optimal strategy. Repeat PN to achieve NSM is aimed at preserving the renal unit, but it is technically demanding and may result in loss of the kidney due to difficulties such as intraoperative bleeding or surgical complications. In addition, as with radical nephrectomy, viable tumour will rarely be found in the resected tissue [45], [54], and [69]. However, repeat PN may be considered with tumours presenting aggressive or high-grade features (eg, Fuhrman grade III–IV, papillary RCC type II, and sarcomatoid differentiation). Radiofrequency ablation and cryotherapy of PSMs after PN are minimally invasive treatment options, but both share the same disadvantages: No tissue is retrieved for histologic evaluation and follow-up is hampered by artificial tissue alterations. According to the data available, watchful waiting seems to be the most appropriate option for the management of PSMs after PN, preserving a maximum of renal units and sparing the patient needless surgery in the majority of cases [9] and [52]. The few patients affected by disease recurrence will benefit from a vigilant surveillance protocol enabling early salvage treatment. However, no validated follow-up scheme exists for patients with PSMs after PN.

4. Conclusions

The achievement of NSMs as a principle of oncologic surgery is of utmost importance and remains the preferential aim of the uro-oncologic surgeon. PSMs in PN occur in 0–7% of cases and seem associated with smaller and endophytic tumours. Gross evaluation of resection margins by the surgeon delivers reliable results, rendering routine frozen-section analysis clinically superfluous. A PSM raises the risk of disease recurrence, especially in tumours of high malignant potential. The lack of large-scale data and of prospective trials including nephrometry scores and long-term follow-up obviates a definitive statement. Intermediate follow-up data available indicate that the majority of patients with PSMs after PN will not experience disease recurrence. Therefore, a surveillance strategy with adherence to a vigilant follow-up protocol seems to be preferable over surgical reintervention.

Author contributions: Martin Marszalek 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: Marszalek, Madersbacher, Van Poppel.

Acquisition of data: Marszalek, Carini, Knüchel, Patard, Van Poppel.

Analysis and interpretation of data: Marszalek, Carini, Knüchel, Madersbacher, Patard, Van Poppel.

Drafting of the manuscript: Marszalek.

Critical revision of the manuscript for important intellectual content: Carini, Chlosta, Jeschke, Kirkali, Knüchel, Madersbacher, Patard, Van Poppel.

Statistical analysis: None.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Marszalek, Van Poppel.

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.

References

  • [1] B.R. Lane, A.F. Fergany, W.M. Linehan, G. Bratslavsky. Should preservable parenchyma, and not tumour size, be the main determinant of the feasibility of partial nephrectomy?. Urology. 2010;76:608-609 Crossref.
  • [2] A.S. Go, G.M. Chertow, D. Fan, C.E. McCulloch, C. Hsu. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-1305 Crossref.
  • [3] C.G. Weight, B.T. Larson, A.F. Fergany, et al. Nephrectomy induced chronic renal insufficiency is associated with increased risk of cardiovascular death and death from any cause in patients with localized cT1b renal masses. J Urol. 2010;183:1317-1323 Crossref.
  • [4] O. Yossepowitch, R.H. Thompson, B.C. Leibovich, et al. Positive surgical margins at partial nephrectomy: predictors and oncological outcomes. J Urol. 2008;179:2158-2163 Crossref.
  • [5] I.S. Gill, S.F. Matin, M.M. Desai, et al. Comparative analysis of laparoscopic versus open partial nephrectomy for renal tumours in 200 patients. J Urol. 2003;170:64-68 Crossref.
  • [6] J.-J. Patard, A.J. Pantuck, M. Crepel, et al. Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication. Eur Urol. 2007;52:148-154 Abstract, Full-text, PDF, Crossref.
  • [7] E.O. Kwon, B.S. Carver, M.E. Snyder, P. Russo. Impact of positive surgical margins in patients undergoing partial nephrectomy for renal cortical tumours. BJU Int. 2007;99:286-289 Crossref.
  • [8] K. Kieran, J.S. Montgomery, S. Daignault, W.W. Roberts, J.S. Wolf. Comparison of intraoperative parameters and perioperative complications of retroperitoneal and transperitoneal approaches to laparoscopic partial nephrectomy: support for a retroperitoneal approach in selected patients. J Endourol. 2007;21:754-759 Crossref.
  • [9] D.A. Lifshitz, S.A. Shikanov, T. Deklaj, et al. Laparoscopic partial nephrectomy: a single-center evolving experience. Urology. 2010;75:282-287 Crossref.
  • [10] J.W. Saranchuk, A.K. Touijer, P. Hakimian, M.E. Snyder, P. Russo. Partial nephrectomy for patients with a solitary kidney: the Memorial Sloan-Kettering experience. BJU Int. 2004;94:1323-1328 Crossref.
  • [11] M. Peycelon, V. Hupertan, E. Comperat, et al. Long-term outcomes after nephron sparing surgery for renal cell carcinoma larger than 4cm. J Urol. 2009;181:35-41 Crossref.
  • [12] R. Zigeuner, F. Quehenberger, K. Pummer, P. Petritsch, G. Hubmer. Long-term results of nephron-sparing surgery for renal cell carcinoma in 114 patients: risk factors for progressive disease. BJU Int. 2003;92:567-571 Crossref.
  • [13] B.J. Scoll, R.G. Uzzo, D.Y. Chen, et al. Robot-assisted partial nephrectomy: a large single-institutional experience. Urology. 2010;75:1328-1334 Crossref.
  • [14] H. Van Poppel, L. Da Pozzo, W. Albrecht, 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;51:1606-1615 Abstract, Full-text, PDF, Crossref.
  • [15] I.S. Gill, L.R. Kavoussi, B.R. Lane, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumours. J Urol. 2007;178:41-46 Crossref.
  • [16] M. Marszalek, H. Meixl, M. Polajnar, M. Rauchenwald, K. Jeschke, S. Madersbacher. Laparoscopic and open partial nephrectomy: a matched-pair comparison of 200 patients. Eur Urol. 2009;55:1171-1178 Abstract, Full-text, PDF, Crossref.
  • [17] E.M. Gong, M.A. Orvieto, K.C. Zorn, A. Lucioni, G.D. Steinberg, A.L. Shalhav. Comparison of laparoscopic and open partial nephrectomy in clinical T1a renal tumours. J Endourol. 2008;22:953-957
  • [18] F. Porpiglia, C. Fiori, C. Terrone, E. Bollito, D. Fontana, R.M. Scarpa. Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery. J Urol. 2005;173:1098-1101 Crossref.
  • [19] S. Permpongkosol, J.R. Colombo Jr., I.S. Gill, L.R. Kavoussi. Positive surgical parenchymal margin after laparoscopic partial nephrectomy for renal cell carcinoma: oncological outcomes. J Urol. 2006;176:2401-2404 Crossref.
  • [20] I.S. Gill, K. Kamoi, M. Aron, M.M. Desai. 800 Laparoscopic partial nephrectomies: a single surgeon series. J Urol. 2010;183:34-42 Crossref.
  • [21] B.M. Benway, S.B. Bhayani, C.G. Rogers, et al. Robot-assisted partial nephrectomy: an international experience. Eur Urol. 2010;57:815-820 Abstract, Full-text, PDF, Crossref.
  • [22] C.G. Rogers, M. Menon, E.S. Weise, et al. Robotic partial nephrectomy: a multi-institutional analysis. J Robotic Surg. 2008;2:141-143 Crossref.
  • [23] A. Mottrie, G. De Naeyer, P. Schatteman, P. Carpentier, M. Sangalli, V. Ficarra. Impact of the learning curve on perioperative outcomes in patients who underwent robotic partial nephrectomy for parenchymal renal tumours. Eur Urol. 2010;58:127-133 Abstract, Full-text, PDF, Crossref.
  • [24] G. Spana, G.P. Haber, L.M. Dulabon, et al. Complications after robotic partial nephrectomy at centers of excellence: multi-institutional analysis of 450 cases. J Urol. 2011;186:417-422 Crossref.
  • [25] R.E. Link, S.B. Bhayani, M.E. Allaf, et al. Exploring the learning curve, pathological outcomes and perioperative morbidity of laparoscopic partial nephrectomy performed for renal mass. J Urol. 2005;173:1690-1694 Crossref.
  • [26] B.M. Benway, S.B. Bhayani, C.G. Rogers, et al. Robot assisted partial nephrectomy versus laparoscopic partial nephrectomy for renal tumours: a multi-institutional analysis of perioperative outcomes. J Urol. 2009;182:866-872
  • [27] R.G. Uzzo, A.C. Novick. Nephron sparing surgery for renal tumours: indications, techniques and outcomes. J Urol. 2001;166:6-18
  • [28] S.E. Sutherland, M.I. Resnick, G.T. Maclennan, H.B. Goldman. Does the size of the surgical margin in partial nephrectomy for renal cell cancer really matter?. J Urol. 2002;167:61-64
  • [29] E.A. Castilla, L.S. Liou, N.A. Abrahams, et al. Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma. Urology. 2002;60:993-997 Crossref.
  • [30] H. Van Poppel, R. Van Reusel. How much margin to spare in partial nephrectomy?. J. De La Rosette, C. Sternberg, H.P. Van Poppel (Eds.) Renal cell cancer: diagnosis and therapy (Springer, London, 2008) 229-235
  • [31] N. Berdjis, O.W. Hakenberg, S. Zastrow, S. Oehlschläger, V. Novotny, M.P. Wirth. Impact of resection margin status after nephron-sparing surgery for renal cell carcinoma. BJU Int. 2006;97:1208-1210 Crossref.
  • [32] N.Y. Piper, J.T. Bishoff, C. Magee, et al. Is a 1-cm margin necessary during nephron-sparing surgery for renal cell carcinoma?. Urology. 2001;586:849-852 Crossref.
  • [33] P. Puppo, C. Introini, P. Calvi, A. Naselli. Long term results of excision of small renal cancer surrounded by a minimal layer of grossly normal parenchyma: review of 94 cases. Eur Urol. 2004;46:477-481 Crossref.
  • [34] Q.-L. Li, H.-W. Guan, Q.-P. Zhang, L.-Z. Zhang, F.-P. Wang, Y.-J. Liu. Optimal margin in nephron-sparing surgery for renal cell carcinoma 4cm or less. Eur Urol. 2003;44:448-451 Crossref.
  • [35] Q.L. Li, L. Cheng, H.W. Guan, Y. Zhang, F.P. Wang, X.S. Song. Safety and efficacy of mini-margin nephron-sparing surgery for renal cell carcinoma 4-cm or less. Urology. 2008;71:924-927 Crossref.
  • [36] A. Minervini, C. di Cristofano, A. Lapini, et al. Histopathologic analysis of peritumoral pseudocapsule and surgical margin status after tumor enucleation for renal cell carcinoma. Eur Urol. 2009;55:1410-1418 Abstract, Full-text, PDF, Crossref.
  • [37] B. Ljungberg, N.C. Cowan, D.C. Hanbury, et al., European Association of Urology Guideline Group. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol. 2010;58:398-406 Abstract, Full-text, PDF, Crossref.
  • [38] M. Carini, A. Minervini, A. Lapini, L. Masieri, S. Serni. Simple enucleation for the treatment of renal cell carcinoma between 4 and 7cm in greatest dimension: progression and long-term survival. J Urol. 2006;175:2022-2026 Crossref.
  • [39] M. Carini, A. Minervini, L. Masieri, A. Lapini, S. Serni. Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year experience. Eur Urol. 2006;50:1263-1271 Abstract, Full-text, PDF, Crossref.
  • [40] A. Minervini, S. Serni, A. Tuccio, et al. Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study. BJU Int. 2011;107:1394-1399 Crossref.
  • [41] A. Minervini, V. Ficarra, F. Rocco, et al. Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study. J Urol. 2011;185:1604-1610 Crossref.
  • [42] D.J. Lee, G. Hruby, M.C. Benson, J.M. McKiernan. Renal function and oncologic outcomes in nephron sparing surgery for renal masses in solitary kidneys. World J Urol. 2011;29:343-348 Crossref.
  • [43] M.F. Wszolek, P.A. Kenney, Y. Lee, J.A. Libertino. Comparison of hilar clamping and non-hilar clamping partial nephrectomy for tumours involving a solitary kidney. BJU Int. 2010;107:1886-1892
  • [44] F. Porpiglia, C. Fiori, R. Bertolo, R.M. Scarpa. Does tumour size really affect the safety of laparoscopic partial nephrectomy?. BJU Int. 2010;108:268-274
  • [45] O. Raz, S. Mendlovic, Y. Shilo, et al. Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron sparing surgery. Urology. 2010;75:277-280 Crossref.
  • [46] A. Breda, S.V. Stepanian, J. Liao, et al. Positive margins in laparoscopic partial nephrectomy in 855 cases: a multi-institutional survey from the United States and Europe. J Urol. 2007;178:47-50 Crossref.
  • [47] I. Frank, J.R. Colombo Jr., M. Rubinstein, M. Desai, J. Kaouk, I.S. Gill. Laparoscopic partial nephrectomy for centrally located renal tumors. J Urol. 2006;175:849-852 Crossref.
  • [48] K. Bensalah, A.J. Pantuck, N. Rioux-Leclercq, et al. Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol. 2010;57:466-473 Abstract, Full-text, PDF, Crossref.
  • [49] R. Venkatesh, K. Weld, C.D. Ames, et al. Laparoscopic partial nephrectomy for renal masses: effect of tumor location. Urology. 2006;67:1169-1174 Crossref.
  • [50] V. Ficarra, G. Novara, S. Secco, et al. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol. 2009;56:786-793 Abstract, Full-text, PDF, Crossref.
  • [51] A. Kutikov, R.G. Uzzo. The R.E.N.A.L. nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol. 2009;182:844-853 Crossref.
  • [52] P.J. Desai, P.E. Andrews, R.G. Ferrigni, E.P. Castle. Laparoscopic partial nephrectomy at the Mayo Clinic Arizona: follow-up surveillance of positive margin disease. Urology. 2008;71:283-286 Crossref.
  • [53] M.A. Lopez-Costea, L. Fumadó, D. Lorente, L. Riera, E.F. Miranda. Positive margins after nephron-sparing surgery for renal cell carcinoma: long-term follow-up of patients on active surveillance. BJU Int. 2010;106:645-648 Crossref.
  • [54] E.R. Ray, B.W. Turney, R. Singh, A. Chandra, D.W. Cranston, T.S. O’Brien. Open partial nephrectomy: outcomes from two UK centres. BJU Int. 2006;97:1211-1215 Crossref.
  • [55] J.-C. Bernhard, A.J. Pantuck, H. Wallerand, et al. Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma. Eur Urol. 2010;57:1080-1086 Abstract, Full-text, PDF, Crossref.
  • [56] R. Bollens, A. Rosenblatt, B.P. Espinoza, et al. Laparoscopic partial nephrectomy with “on-demand” clamping reduces warm ischemia time. Eur Urol. 2007;52:804-810 Abstract, Full-text, PDF, Crossref.
  • [57] M. Duvdevani, Y. Mor, A. Kastin, et al. Renal artery occlusion during nephron-sparing surgery: retrospective review of 301 cases. Urology. 2006;68:960-963 Crossref.
  • [58] G.L. Smith, P.A. Kenney, Y. Lee, et al. Non-clamped partial nephrectomy: techniques and surgical outcomes. BJU Int. 2011;107:1054-1058 Crossref.
  • [59] T.T. Nguyen, J.P. Parkinson, D.M. Kuehn, H.N. Winfield. Technique for ensuring negative surgical margins during laparoscopic partial nephrectomy. J Endourol. 2005;19:410-415 Crossref.
  • [60] T.J. Polascik, M.V. Meng, J.I. Epstein, F.F. Marshall. Intraoperative sonography for the evaluation and management of renal tumors: experience with 100 patients. J Urol. 1995;154:1676-1680
  • [61] S. Tobis, J. Knopf, C. Silver, et al. Near infrared fluorescence imaging with robotic assisted laparoscopic partial nephrectomy: initial clinical experience for renal cortical tumors. J Urol. 2011;186:47-52 Crossref.
  • [62] D. Teber, S. Guven, T. Simpfendörfer, et al. Augmented reality: a new tool to improve surgical accuracy during laparoscopic partial nephrectomy? Preliminary in vitro and in vivo results. Eur Urol. 2009;56:332-338 Abstract, Full-text, PDF, Crossref.
  • [63] M.E. Allaf, S.B. Bhayani, C. Rogers, et al. Laparoscopic partial nephrectomy: evaluation of long-term oncological outcome. J Urol. 2004;172:871-873 Crossref.
  • [64] M. Duvdevani, M. Laufer, A. Kastin, et al. Is frozen section analysis in nephron sparing surgery necessary? A clinicopathological study of 301 cases. J Urol. 2005;173:385-387 Crossref.
  • [65] D.J. Kubinski, P.E. Clark, D.G. Assimos, M.C. Hall. Utility of frozen section analysis of resection margins during partial nephrectomy. Urology. 2004;64:31-34 Crossref.
  • [66] Z. Kirkali, F. Algaba, M. Scarpelli, I. Trias, F.P. Selvaggi, H. Van Poppel. What does the urologist expect from the pathologist (and what can the pathologists give) in reporting on adult kidney tumour specimens?. Eur Urol. 2007;51:1194-1201 Abstract, Full-text, PDF, Crossref.
  • [67] I.S. Hagemann, J.S. Lewis Jr. A retrospective comparison of 2 methods of intraoperative margin evaluation during partial nephrectomy. J Urol. 2009;181:500-505 Crossref.
  • [68] M.O. Timsit, J.P. Bazin, N. Thiounn, et al. Prospective study of safety margins in partial nephrectomy: intraoperative assessment and contribution of frozen section analysis. Urology. 2006;67:923-926 Crossref.
  • [69] V. Sundaram, R.S. Figenshau, T.M. Roytman, et al. Positive margin during partial nephrectomy: does cancer remain in the renal remnant?. Urology. 2011;77:1400-1403 Crossref.

Footnotes

a Department of Urology and Andrology, Donauspital, Vienna, Austria

b Department of Urology, Graz Medical University, Graz, Austria

c Department of Urology, University of Florence, Careggi Hospital, Florence, Italy

d Department of Urology, Institute of Oncology, Kielce, Poland

e Department of Urology, Klagenfurt General Hospital, Klagenfurt, Austria

f Department of Urology, Dokuz Eylul University School of Medicine, Izmir, Turkey

g Institute of Pathology, Aachen University, Aachen, Germany

h Department of Urology, Bicêtre Hospital, Paris XI University, Kremlin Bicêtre, France

i Department of Urology, University Hospital Leuven, Leuven, Belgium

lowast Corresponding author. Department of Urology and Andrology, Sozialmedizinisches Zentrum Ost - Donauspital, Langobardenstrasse 122, A-1220 Vienna, Austria.