Radiofrequency Ablation of T1a Renal Cell Carcinomas within Renal Transplant Allografts: Oncologic Outcomes and Graft Viability

CLINICAL STUDY

Radiofrequency Ablation of T1a Renal Cell Carcinomas within Renal Transplant Allografts: Oncologic Outcomes and Graft Viability Derek W. Cool, MD, PhD, FRCPC, and John R. Kachura, MD, FRCPC, FSIR

ABSTRACT Purpose: To evaluate oncologic outcomes and graft viability after percutaneous RF ablation of renal cell carcinoma (RCC) developing within renal transplant allografts. Materials and Methods: A single-institution, retrospective study reviewed all patients treated with RF ablation for RCC between February 2004 and May 2016. Ten patients were identified (age 49.6 y ± 12.6; 9 men, 1 woman) with 12 biopsy-confirmed RCC tumors within the allograft (all T1a, mean diameter 2.0 cm ± 0.7). Mean time from transplant to RCC diagnosis was 13.2 years ± 6.3. RF ablation was performed on an outpatient basis using conscious sedation. Procedural efficacy, complications, oncologic outcomes, and allograft function were evaluated. Statistical analysis with t tests and Pearson correlation compared allograft function before and after RF ablation and impact of proportional ablation size to allograft volume on function after ablation. Results: Technical success rate and primary technique efficacy were 100% (12/12). No local or distant RCC progression was seen at mean follow-up of 54.3 months ± 38.7 (range, 9–136 months). Graft failure requiring hemodialysis or repeat transplantation occurred in 3 patients (26, 354, and 750 d after RF ablation), all of whom had glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 before ablation. For all patients, mean GFR 6 months after RF ablation (35.8 mL/min/1.73 m2 ± 17.7) was not significantly different (P ¼ .8) from preprocedure GFR (36.2 mL/min/1.73 m2 ± 14.3). Proportional volume of allograft that was ablated did not correlate with immediate or long-term GFR changes. One patient died of unrelated comorbidities 52 months after ablation. No major complications occurred. Conclusions: RF ablation of renal allograft RCC provided effective oncologic control without adverse impact on graft viability.

ABBREVIATIONS GFR ¼ glomerular filtration rate, RCC ¼ renal cell carcinoma

The development of renal cell carcinoma (RCC) within transplant allografts is rare, with an estimated incidence of 0.18%–0.26% (1–3). A meta-analysis of renal allograft RCC treatment identified 267 de novo RCC tumors reported in 70

From the Division of Vascular and Interventional Radiology, Department of Medical Imaging, University of Toronto, University Health Network, 200 Elizabeth St., Toronto, M5G 2C4, Canada. Received April 25, 2017; final revision received July 17, 2017; accepted July 23, 2017. Address correspondence to D.W.C.; E-mail: [email protected] Neither of the authors has identified a conflict of interest. From the SIR 2017 Annual Scientific Meeting. © SIR, 2017 J Vasc Interv Radiol 2017; ▪:1–6 http://dx.doi.org/10.1016/j.jvir.2017.07.023

publications between 1992 and December 2014, most of which were case reports and small case series (2). Nephronsparing treatment in transplant-dependent patients with allograft RCCs is preferred to achieve oncologic control while maintaining graft viability. Radiofrequency (RF) ablation has shown excellent outcomes for RCC within native kidneys, with 5-year survival rates of 90%–95% (4–6). However, the applicability of these results to patients with renal transplants cannot be assumed, as the histologic makeup of allograft RCCs differs from RCCs seen in native kidneys. Patients with renal transplants have a higher proportion of papillary subtype histology (43%–75% of RCC cases) (2,3,7). Furthermore, the impact of RF ablation on graft viability is unknown. This study evaluated the intermediate-term oncologic outcomes and graft viability from a single-center experience of RF ablation of 12 allograft RCC tumors. The transplant allograft function was

2 ▪ RF Ablation of RCC within Renal Transplant Allografts

evaluated to determine possible impact of RF ablation on graft viability.

MATERIALS AND METHODS Institutional research ethics review board approval was obtained to perform this retrospective study. All renal RF ablation procedures performed in 355 patients between February 2004 and May 2016 were reviewed. The mean number of renal transplant surgeries performed at this institution during the study period was 153 kidneys/y ± 20 (range, 115–190 kidneys/y). Ten renal transplant patients (mean age 49.6 y ± 12.6; range, 28–66 y; 9 men and 1 woman) were identified with 12 de novo allograft RCC tumors (2.0 cm ± 0.7; range, 1.0–3.1 cm). All tumors were found incidentally during annual Doppler ultrasound (US) scanning for transplant surveillance. Of 10 patients, 9 were Eastern Cooperative Oncology Group 0 and 1 was Eastern Cooperative Oncology Group 1. Eight patients had solitary tumors, and 2 patients had synchronous tumors (mean R.E.N.A.L. Nephrometry score 6.5 ± 1.6; range, 4–10) (8). All patients had confirmed RCC on core biopsy. The mean time from transplantation to RCC diagnosis was

Cool and Kachura ▪ JVIR

13.2 years ± 6.3 (range, 0.8–21.1 y). All patients had functioning renal transplants before RF ablation with immunosuppression regimens that included prednisone and 1 or a combination of the following agents: tacrolimus, cyclosporine, or mycophenolate. Patient demographics and tumor characteristics are listed in the Table. Patients were selected for RF ablation after discussion at a biweekly multidisciplinary tumor board where other treatment options, such as active surveillance, partial nephrectomy, or transplantectomy, were considered. The institutional preference for patients with T1a renal tumors (< 4 cm) diagnosed after transplant and functioning allografts is thermal ablation therapy; at the time of this study, RF ablation was the only thermal therapy available at the institution. All RF ablation procedures were performed by 1 operator (J.R.K.) with 17 years of RF ablation experience. The procedures were performed percutaneously on an outpatient basis with conscious sedation using intravenous fentanyl and midazolam. Immunosuppression medications were not modified before or after the procedure, and prophylactic antibiotics were not administered. The same multitined RF electrode system (LeVeen; Boston Scientific, Marlborough,

Table. Individual Patient and Tumor Characteristics Sex

Age (y) at Diagnosis

Type of Transplant

RCC Subtype*

Tumor Diameter (cm)

Tumor Location†

Transplant Outcome

M

60

Cadaveric

Papillary, grade 2

3.1

Lower pole, exophytic, 4 mm

M

45

Cadaveric

Papillary, grade 2

1.0

Interpolar, exophytic

Graft failure requiring repeat transplant 11.8 months after RF ablation

F

44

Livingrelated

Papillary, grade 2

2.9

Upper pole, exophytic, 7 mm

Graft failure requiring dialysis 25 months after RF ablation. Transplantectomy for benign adenomas on failed transplant

M

55

Livingrelated

Papillary, grade 1

3.0

Upper pole, exophytic, 6 mm

Died 51.6 months after RF ablation without chronic graft failure or identified RCC recurrence

M

59

Cadaveric

Papillary, grade 2

1.4, 1.7

M

50

Livingrelated

Papillary, grade 1

2.2

M

58

Cadaveric

Papillary, g rade 2

2.1, 1.8

Lower pole, exophytic, < 1 mm and interpolar, exophytic, < 1 mm

M

28

Livingrelated

Tubulocystic, grade 1

1.5 cm

Upper pole, exophytic, 4 mm

M

31

Livingrelated

Papillary, grade 1

1.4 cm

Interpolar, mixed exophytic and endophytic, 14 mm

M

66

Cadaveric

Papillary, grade 2

2.3

Interpolar, parenchymal, 3 mm

Interpolar, exophytic, 1 mm and lower pole, exophytic, 3 mm Lower pole, parenchymal, < 1 mm

F ¼ female; M ¼ male; RCC ¼ renal cell carcinoma. *From core biopsy. † Pole, parenchyma location, minimum distance to renal collecting system.

Graft failure requiring dialysis 26 days after RF ablation.

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

Massachusetts) was used for all ablations. The electrode tine diameter was selected for a circumferential tumor ablation margin of 5–10 mm (tine diameters used: 3 cm  1, 3.5 cm  9, 4 cm  2). All electrodes were inserted under US guidance. Noncontrast computed tomography was performed to confirm appropriate electrode position and ensure adequate separation from adjacent structures before beginning ablation. US alone was used to monitor ablation volume progression and completion. Impedance-based ablations were performed according to the manufacturer’s protocol with 2 energy delivery phases performed per electrode position (peak energies: 190–200 W for phase 1 and 133–140 W for phase 2). The endpoint for each phase was impedance roll-off, defined as measured impedance increasing to > 400 Ω. Mean total ablation time per tumor was 10.0 minutes ± 4.1 (range, 5.5–17.6 min). All tumors were ablated using a single electrode position except for a 3.0-cm upper pole tumor that required 2 overlapping electrode positions. The 2 patients with synchronous tumors had RF ablation of both tumors in a single session. No concomitant agents or combination or concurrent therapies were added to the ablation. Clinical and imaging follow-up with the treating interventional radiologist occurred at 2 months, 6–8 months, and 1 year after ablation and annually thereafter. Imaging surveillance was performed with contrast-enhanced US (7 of 10 patients), triphasic contrast-enhanced computed tomography (2 of 10 patients), or multiphase gadolinium-enhanced magnetic resonance imaging (1 of 10 patients). Contrastenhanced US is generally the preferred imaging modality for patients with transplants and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 owing to the low risk of the US contrast material. All imaging interpretation was performed by subspecialized abdominal radiologists working at a large academic tertiary care center. Established ablation terminology and reporting guidelines were followed (9,10). Technical success was defined as the ability to perform the intended ablation therapy with complete coverage of the tumor by the echogenic ablation margin on US. Primary technique efficacy was assessed at the first follow-up examination (typically 2 months after ablation) and was defined as complete coverage of the tumor by the ablation coagulation zone without any enhancement to suggest residual viable tumor. Local tumor progression was defined as new enhancement within a previously successfully treated RCC tumor. Procedure-related complications were categorized using the Society of Interventional Radiology (SIR) classification system and divided into immediate (within 24 h after ablation), periprocedural (within 30 d after ablation), and delayed (> 30 d after ablation) events (11). The impact of RF ablation on transplant allograft function was evaluated using creatinine levels and estimated GFR levels collected before and after ablation. GFR was calculated using the MDRD (Modification of Diet in Renal Disease) Study equation (12). A paired Student t test was used to assess for significant change in renal function after

3

ablation, and the assumption of paired difference normality was confirmed with Q–Q plot and Shapiro-Wilk test. The proportion of the total renal transplant volume ablated during RF ablation was estimated and compared with the change in GFR after RF ablation using Pearson product correlation. Total renal volume was calculated from the US measurements using a prolate ellipsoid formula (height  width  length  π/6) (13,14). Ablation volume was estimated with the ellipsoid formula based on the manufacturer’s expected ablation dimensions. A 2-tailed t test compared the proportion of the renal transplant ablated between patients with functioning transplants and patients who required dialysis or repeat transplant after RF ablation. Statistical analysis was performed with SAS Studio 3.5 (SAS Institute Inc, Cary, North Carolina). Time to dialysis or repeat transplant was also recorded.

RESULTS All 10 patients were successfully treated on an outpatient basis with a technical success rate of 100% (12 of 12 tumors). Ancillary procedures were performed in 5 of the 10 patients to avoid collateral thermal injury to adjacent structures. In 4 patients, peritransplant air and 5% dextrose solution hydropneumodissection was performed for small bowel, colonic, or abdominal wall muscle protection (Fig 1a–c). Air was used rather than carbon dioxide, as it was readily available, and given the relatively small volume, it was unlikely to cause significant pneumoperitoneum pain as seen in laparoscopy (15). The final patient had chilled saline infused through a percutaneous nephrostomy catheter (700 mL over 30 min or 23 mL/min) for thermal protection of the proximal ureter that was located < 1 mm from a 3.1-cm partially posteriorly exophytic tumor (Fig 1a–c). A Foley catheter was inserted to ensure continuous drainage of the chilled saline from the bladder. No major complications occurred, and no patients required hospital admission or emergency dialysis. Two patients developed minor, transient numbness in the ipsilateral groin and lateral thigh (presumed genitofemoral nerve injury) after RF ablation in right lower quadrant transplants. The patient’s functional capacity was not limited in either case, and both cases resolved within 1 year after RF ablation (SIR class A complication—no therapy, no consequence). All tumors showed complete coagulation without residual enhancement on imaging performed 2 months after ablation (primary technique efficacy ¼ 100%). Mean follow-up time after ablation was 54.3 months ± 38.7 (median 42.7 months; range, 9–136 months) without any evidence of local tumor progression or RCC recurrence. One patient died 4.3 years after RF ablation. The cause of the death was not available for review from an outside hospital; however, the patient died without known RCC recurrence, and the GFR was 54 mL/min/1.73 m2 8 days before his death. A transplantectomy was performed on another patient for multiple new tumors that developed within the allograft, which had ceased functioning 2.1 years after RF ablation. The new

4 ▪ RF Ablation of RCC within Renal Transplant Allografts

Cool and Kachura ▪ JVIR

Figure 1. Transplant allograft ablation challenges. (a) A 60-year-old man with exophytic lower pole RCC (arrowheads) located < 1 mm from ureter (arrow). (b) Percutaneous nephrostomy and bladder Foley catheter insertion provided continuous chilled saline ureter irrigation during ablation. (c) A 50-year-old man with lower pole RCC (arrowhead) contacting abdominal oblique muscles. Hydropneumodissection was performed for thermal protection without any pain or muscle injury after RF ablation.

allograft tumors were benign adenomas on final pathology; histologic assessment of the RCC tumor previously treated with RF ablation demonstrated complete coagulation without any viable malignancy. Transplant allograft renal function did not significantly change after RF ablation (P ¼.8) with mean GFR levels 6 months before and 6 months after treatment of 36.2 mL/min/ 1.73 m2 ± 14.3 and 35.8 mL/min/1.73 m2 ± 17.7, respectively (Fig 2). Of the 5 patients (60%) with at least 1 GFR level < 30 mL/min/1.73 m2 within the 6 months before RF ablation, 3 developed graft failure requiring dialysis or repeat transplant. The time to dialysis or transplant after RF ablation in the 3 patients was 26 days, 355 days, and 750 days. The ages of the grafts at the time of RF ablation were 11.9 years, 21.7 years, and 12.6 years, with tumor sizes of 1.5 cm, 1.0 cm, and 2.9 cm. The other 2 patients with GFR < 30 mL/min/1.73 m2 before RF ablation have functioning transplants at 9 and 24 months after RF ablation. The patient who required dialysis 26 days after RF ablation had a pre-existing failing graft with a GFR that had steadily declined from 37 mL/min/1.73 m2 to 15 mL/min/1.73 m2 in the 14 months before RF ablation. RF ablation was chosen over surgical transplant removal for

this patient in hopes of prolonging any remaining graft function. None of the 5 patients with GFR levels > 30 mL/ min/1.73 m2 before RF ablation have required dialysis or repeat transplant at a median follow-up of 48 months (range, 15–136 months). The mean estimated RF ablation volume to transplant allograft volume ratio was not significantly different (p ¼ .32) for the patients who required dialysis or transplant (11.3% ± 4.1) and the patients with preserved function (13.1% ± 3.8). No correlation was found between the proportion of transplant graft ablated and the GFR changes after RF ablation at 6 months or the duration of clinical follow-up (r ¼ .2 and r ¼ .3).

DISCUSSION In this study, RF ablation of RCC T1a tumors within transplant allografts provided excellent oncologic control with no clear adverse impact on transplant allograft function. No recurrences occurred for any of the 12 treated tumors at a mean follow-up of 4.5 years. Outcomes of RF ablation treatment of RCC tumors within allografts in the literature have mostly been limited to single-center case series of 3–5 patients with a mean follow-up of < 3 years

Volume ▪ ▪ Number ▪ ▪ Month ▪ 2017

Figure 2. Scatterplot of mean renal function GFR in 6 months before and 6 months after RF ablation with line of equality overlaid.

(7,16–20). The meta-analysis by Tillou et al (2) identified 17 published reports describing 48 patients with RCC tumors within transplant allografts treated with RF ablation or cryoablation (38 patients with RF ablation and 10 patients with cryoablation). The meta-analysis reported a mean follow-up of 1.7 years ± 1.6 with the largest single-center study having 5 patients treated with RF ablation (21). One local recurrence was found in the 48 tumors treated with RF ablation or cryoablation (mean follow-up 1.7 y ± 1.6), which occurred 24 months after RF ablation of a 3.2-cm papillary RCC (2). The mean tumor diameter in this study was similar to that of the meta-analysis (2.0 cm ± 0.7 and 2.1 cm ± 0.8, respectively) (2). The impact of RF ablation on the long-term viability of renal transplant function is unknown and was not addressed in the meta-analysis (2). In this study, 3 patients (30%) developed graft failure that required long-term dialysis or repeat transplantation; all 3 patients had chronically elevated creatinine levels with at least 1 estimated GFR value < 30 mL/min/1.73 m2 within 6 months before RF ablation. For all patients, the mean GFR did not significantly change 6 months before and 6 months after RF ablation, and there was no correlation between the proportion of the total transplant volume that was ablated and the decrease in GFR; this suggests that RF ablation is likely not a major factor impacting long-term graft viability. A retrospective study comprising 20 patients (15 receiving RF ablation and 5 receiving cryoablation) in 11 centers in 5 countries demonstrated no significant change in creatinine clearance 3 months before ablation and 3 months after ablation (7). Nephron-sparing partial nephrectomy is an alternative to thermal ablation and has been reported in 95 patients (mean

5

follow-up 2.7 y ± 2.1) with 1 local recurrence that occurred 12 months postoperatively (2). Tillou et al (22) presented the largest multicenter study comprising 43 patients who had nephron-sparing resections of renal masses within the transplant allograft (41 of which were RCC). There was no disease recurrence in the cohort (mean follow-up 2.4 y; range, 0.1–9.2 y); 1 patient developed graft failure requiring dialysis (22). Surgical resection, instead of ablation, can be more challenging in a transplanted kidney, as adhesions and postsurgical scarring make safe mobilization of the allograft more difficult (23). In the meta-analysis, the rate of complications requiring some form of treatment (Clavien grade II or higher) after nephron-sparing surgery was 10.8% compared with 4.7% for thermal ablation (RF ablation and cryoablation—urinary infection and abscess) (2,24). In the present study, all procedures were performed on an outpatient basis, and no complications occurred after RF ablation that required treatment, hospitalization, or intervention. Papillary RCC represents a disproportionately higher percentage of RCC tumors in patients with renal transplants and hemodialysis compared with the normal population (2,3), and it represented 92% of the treated tumors in this study. Other published studies of transplant allograft RCC treated with RF ablation had rates of papillary RCC of 57.1%–75% (2,7). Although it has been suggested that papillary RCC is less aggressive than clear cell RCC, the impact of the histologic subtype on prognosis for similar stage of disease remains controversial (25–29). Limitations of this study include the retrospective nature, small sample size, and lack of a comparative control group. A prospective study is likely impractical given the disease rarity; however, the retrospective nature may not have captured all patients with transplant allograft RCCs, as some may have proceeded to nephrectomy (especially larger tumors) or been monitored on active surveillance—leading to selection bias. All the treated tumors were T1a RCCs ( 3.1 cm); therefore, the oncologic outcome and allograft function after RF ablation of larger renal masses ( 4 cm) cannot be assumed. As a single-center, single-operator study, the clinical outcomes may not be reproducible for the broader population of academic and nonacademic practices. Furthermore, any complication or recurrence after RF ablation that may have been managed at an outside center would have been recorded only if the patient communicated that information during the routine follow-up clinic visits with the treating interventional radiologist (recall bias). Finally, although this study has the longest published mean follow-up time for thermal ablation in transplant allografts (4.5 y), long-term data (> 5 y) are needed. In conclusion, RF ablation of small RCC tumors within renal transplant allografts provides excellent oncologic control without clear evidence of adversely affecting graft function. Further evaluation of long-term RF ablation outcomes and prospective comparison of RF ablation with other treatment modalities (eg, cryoablation, partial nephrectomy) for small ( 4 cm) and medium-sized (4–5 cm) tumors would be helpful.

6 ▪ RF Ablation of RCC within Renal Transplant Allografts

REFERENCES 1. Ianhez LE, Lucon M, Nahas WC, et al. Renal cell carcinoma in renal transplant patients. Urology 2007; 69:462–464. 2. Tillou X, Guleryuz K, Collon S, Doerfler A. Renal cell carcinoma in functional renal graft: toward ablative treatments. Transplant Rev (Orlando) 2016; 30:20–26. 3. Troxell ML, Higgins JP. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma. Hum Pathol 2016; 57: 28–36. 4. Psutka SP, Feldman AS, McDougal WS, McGovern FJ, Mueller P, Gervais DA. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol 2013; 63:486–492. 5. Olweny EO, Park SK, Tan YK, Best SL, Trimmer C, Cadeddu JA. Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up. Eur Urol 2012; 61:1156–1161. 6. Zhang F, Chang X, Liu T, et al. Prognostic factors for long-term survival in patients with renal-cell carcinoma after radiofrequency ablation. J Endourol 2016; 30:37–42. 7. Cornelis F, Buy X, Andre M, et al. De novo renal tumors arising in kidney transplants: midterm outcome after percutaneous thermal ablation. Radiology 2011; 260:900–907. 8. Kutikov A, Uzzo RG. 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. 9. Ahmed M, Solbiati L, Brace CL, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria—a 10-year update. Radiology 2014; 273:241–260. 10. Clark TW, Millward SF, Gervais DA, et al. Reporting standards for percutaneous thermal ablation of renal cell carcinoma. J Vasc Interv Radiol 2009; 20(7 Suppl):S409–S416. 11. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14(9 Pt 2): S199–S202. 12. 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; 130:461–470. 13. Jones TB, Riddick LR, Harpen MD, Dubuisson RL, Samuels D. Ultrasonographic determination of renal mass and renal volume. J Ultrasound Med 1983; 2:151–154. 14. Mancini M, Mainenti PP, Speranza A, et al. Accuracy of sonographic volume measurements of kidney transplant. J Clin Ultrasound 2006; 34: 184–189.

Cool and Kachura ▪ JVIR

15. Ikechebelu JI, Obi RA, Udigwe GO, Joe-Ikechebelu NN. Comparison of carbon dioxide and room air pneumoperitoneum for day-case diagnostic laparoscopy. J Obstet Gynaecol 2005; 25:172–173. 16. Su MZ, Campbell NA, Lau HM. Management of renal masses in transplant allografts at an Australian kidney-pancreas transplant unit. Transplantation 2014; 97:654–659. 17. Christensen SF, Hansen JM. Donor kidney with renal cell carcinoma successfully treated with radiofrequency ablation: a case report. Transplant Proc 2015; 47:3031–3033. 18. Swords DC, Al-Geizawi SM, Farney AC, et al. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution. Clin Transplant 2013; 27:E199–E205. 19. Veltri A, Grosso M, Castagneri F, et al. Radiofrequency thermal ablation of small tumors in transplanted kidneys: an evolving nephron-sparing option. J Vasc Interv Radiol 2009; 20:674–679. 20. Olivani A, Iaria M, Missale G, et al. Percutaneous ultrasound-guided radiofrequency ablation of an allograft renal cell carcinoma: a case report. Transplant Proc 2011; 43:3997–3999. 21. Vegso G, Toronyi E, Deak PA, Doros A, Langer RM. Detection and management of renal cell carcinoma in the renal allograft. Int Urol Nephrol 2013; 45:93–98. 22. Tillou X, Guleryuz K, Doerfler A, et al. Nephron sparing surgery for De Novo kidney graft tumor: results from a multicenter national study. Am J Transplant 2014; 14:2120–2125. 23. Ribal MJ, Rodriguez F, Musquera M, et al. Nephron-sparing surgery for renal tumor: a choice of treatment in an allograft kidney. Transplant Proc 2006; 38:1359–1362. 24. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240:205–213. 25. Zucchi A, Novara G, Costantini E, et al. Prognostic factors in a large multiinstitutional series of papillary renal cell carcinoma. BJU Int 2012; 109: 1140–1146. 26. Pignot G, Elie C, Conquy S, et al. Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. Urology 2007; 69:230–235. 27. Gontero P, Ceratti G, Guglielmetti S, et al. Prognostic factors in a prospective series of papillary renal cell carcinoma. BJU Int 2008; 102: 697–702. 28. Nguyen DP, Vertosick EA, Corradi RB, et al. Histological subtype of renal cell carcinoma significantly affects survival in the era of partial nephrectomy. Urol Oncol 2016; 34:259.e1–259.e8. 29. Crepel M, Isbarn H, Capitanio U, et al. Does histologic subtype affect oncologic outcomes after nephron-sparing surgery? Urology 2009; 74: 842–845.