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Nephron sparing surgery in von Hippel-Lindau associated renal cell carcinoma; clinicopathological long-term follow-up

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Abstract

We evaluated the clinicopathological outcome of von Hippel-Lindau (VHL)-patients who had mainly undergone nephron sparing surgery (NSS) for renal cell carcinoma (RCC) when the tumour diameter has reached 4.0 cm. Multiple, bilateral RCC with high recurrence rates and subsequent repeated interventions, followed by increasing risk for end-stage renal failure and metastases is characteristic for VHL. NSS is widely used for VHL-associated RCC at 3.0 cm cut-off. 54 VHL patients underwent NSS, nephrectomy or thermal ablation for RCC. We analysed time to second treatment, overall and cancer specific survival, intra- and post-operative data as well as tumour characteristics. We also examined the effects of delaying removal of RCC to 4.0 cm cut-off. Median follow-up was 67 months. 54 patients underwent 97 kidney treatments. 96 % of first and 67 % of second interventions comprised of NSS. 0 % metastases were observed in the group with largest tumour size ≤4 cm. The probability for second surgery was 21 %, at 5 years and 42 % at 10 years. Median time to second NSS was 149.6 months. The overall and cancer specific survival rate was 96.5 and 100 % at 5-year follow-up, and 82.5 and 90.5 % respectively at 10-year follow-up. Median delay to second NSS at 4.0 cm cut-off versus 3.0 cm was 27.8 months. NSS was both successfully used in first and second surgery and to some extent even in third surgery. By following a strict surveillance protocol it is possible to support a 4.0 cm-threshold strategy for NSS, based on the assumption that delaying time to second NSS prevents patients from premature renal failure.

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Abbreviations

VHL:

von Hippel-Lindau

NSS:

Nephron sparing surgery

RCC:

Renal cell carcinoma

RFTA:

Radio frequency thermal ablation

SD:

Standard deviation

CI:

Confidence interval

References

  1. Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, Ferguson-Smith MA (1990) Clinical features and natural history of von Hippel-Lindau disease. Q J Med 77(283):1151–1163

    Article  PubMed  CAS  Google Scholar 

  2. Goldfarb DA, Neumann HP, Penn I, Novick AC (1997) Results of renal transplantation in patients with renal cell carcinoma and von Hippel-Lindau disease. Transplantation 64(12):1726–1729

    Article  PubMed  CAS  Google Scholar 

  3. Gnarra JR, Glenn GM, Latif F, Anglard P, Lerman MI, Zbar B, Linehan WM (1993) Molecular genetic studies of sporadic and familial renal cell carcinoma. Urol Clin North Am 20(2):207–216

    PubMed  CAS  Google Scholar 

  4. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L et al (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260(5112):1317–1320

    Article  PubMed  CAS  Google Scholar 

  5. Neumann HP, Wiestler OD (1991) Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet 337(8749):1052–1054

    Article  PubMed  CAS  Google Scholar 

  6. Whaley JM, Naglich J, Gelbert L, Hsia YE, Lamiell JM, Green JS, Collins D, Neumann HP, Laidlaw J, Li FP et al (1994) Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma. Am J Hum Genet 55(6):1092–1102

    PubMed  CAS  Google Scholar 

  7. Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin MA et al (2009) Patterns of gene expression and copy-number alterations in von Hippel-Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res 69(11):4674–4681

    Article  PubMed  CAS  Google Scholar 

  8. Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN (2003) Human gene mutation database (HGMD): 2003 update. Hum Mutat 21(6):577–581

    Article  PubMed  CAS  Google Scholar 

  9. Beroud C, Joly D, Gallou C, Staroz F, Orfanelli MT, Junien C (1998) Software and database for the analysis of mutations in the VHL gene. Nucleic Acids Res 26(1):256–258

    Article  PubMed  CAS  Google Scholar 

  10. Nordstrom-O’Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, van Brussel A, Voest EE, Giles RH (2010) Genetic analysis of von Hippel-Lindau disease. Hum Mutat 31(5):521–537

    PubMed  Google Scholar 

  11. Neumann HP, Bender BU, Berger DP, Laubenberger J, Schultze-Seemann W, Wetterauer U, Ferstl FJ, Herbst EW, Schwarzkopf G, Hes FJ et al (1998) Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma. J Urol 160(4):1248–1254

    Article  PubMed  CAS  Google Scholar 

  12. Filling-Katz MR, Choyke PL, Oldfield E, Charnas L, Patronas NJ, Glenn GM, Gorin MB, Morgan JK, Linehan WM, Seizinger BR et al (1991) Central nervous system involvement in von Hippel-Lindau disease. Neurology 41(1):41–46

    Article  PubMed  CAS  Google Scholar 

  13. Neumann HP, Eggert HR, Scheremet R, Schumacher M, Mohadjer M, Wakhloo AK, Volk B, Hettmannsperger U, Riegler P, Schollmeyer P et al (1992) Central nervous system lesions in von Hippel-Lindau syndrome. J Neurol Neurosurg Psychiatr 55(10):898–901

    Article  PubMed  CAS  Google Scholar 

  14. Walther MM, Choyke PL, Glenn G, Lyne JC, Rayford W, Venzon D, Linehan WM (1999) Renal cancer in families with hereditary renal cancer: prospective analysis of a tumor size threshold for renal parenchymal sparing surgery. J Urol 161(5):1475–1479

    Article  PubMed  CAS  Google Scholar 

  15. USRDS (2010) Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD

  16. Walther MM, Lubensky IA, Venzon D, Zbar B, Linehan WM (1995) Prevalence of microscopic lesions in grossly normal renal parenchyma from patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no renal disease: clinical implications. J Urol 154(6):2010–2014; discussion 2014–2015

    Google Scholar 

  17. Herring JC, Enquist EG, Chernoff A, Linehan WM, Choyke PL, Walther MM (2001) Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience. J Urol 165(3):777–781

    Article  PubMed  CAS  Google Scholar 

  18. Joly D, Mejean A, Correas JM, Timsit MO, Verkarre V, Deveaux S, Landais P, Grunfeld JP, Richard S (2011) Progress in nephron sparing therapy for renal cell carcinoma and von Hippel-Lindau disease. J Urol 185(6):2056–2060

    Article  PubMed  Google Scholar 

  19. Roupret M, Hopirtean V, Mejean A, Thiounn N, Dufour B, Chretien Y, Chauveau D, Richard S (2003) Nephron sparing surgery for renal cell carcinoma and von Hippel-Lindau’s disease: a single center experience. J Urol 170(5):1752–1755

    Article  PubMed  Google Scholar 

  20. Ploussard G, Droupy S, Ferlicot S, Ples R, Rocher L, Richard S, Benoit G (2007) Local recurrence after nephron-sparing surgery in von Hippel-Lindau disease. Urology 70(3):435–439

    Article  PubMed  Google Scholar 

  21. Duffey BG, Choyke PL, Glenn G, Grubb RL, Venzon D, Linehan WM, Walther MM (2004) The relationship between renal tumor size and metastases in patients with von Hippel-Lindau disease. J Urol 172(1):63–65

    Article  PubMed  Google Scholar 

  22. Matin SF, Ahrar K, Wood CG, Daniels M, Jonasch E (2008) Patterns of intervention for renal lesions in von Hippel-Lindau disease. BJU Int 102(8):940–945

    Article  PubMed  Google Scholar 

  23. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213

    Article  PubMed  Google Scholar 

  24. Becker F, Van Poppel H, Hakenberg OW, Stief C, Gill I, Guazzoni G, Montorsi F, Russo P, Stockle M (2009) Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol 56(4):625–634

    Article  PubMed  Google Scholar 

  25. Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF, Sinescu IC (2010) EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 58(3):398–406

    Article  PubMed  Google Scholar 

  26. Johnson A, Sudarshan S, Liu J, Linehan WM, Pinto PA, Bratslavsky G (2008) Feasibility and outcomes of repeat partial nephrectomy. J Urol 180(1):89–93 (discussion 93)

    Google Scholar 

  27. Shuin T, Yamasaki I, Tamura K, Okuda H, Furihata M, Ashida S (2006) Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment. Jpn J Clin Oncol 36(6):337–343

    Article  PubMed  Google Scholar 

  28. Rocco MV, Frankenfield DL, Hopson SD, McClellan WM (2006) Relationship between clinical performance measures and outcomes among patients receiving long-term hemodialysis. Ann Int Med 145(7):512–519

    PubMed  Google Scholar 

  29. Gupta GN, Peterson J, Thakore KN, Pinto PA, Linehan WM, Bratslavsky G (2010) Oncological outcomes of partial nephrectomy for multifocal renal cell carcinoma greater than 4 cm. J Urol 184(1):59–63

    Article  PubMed  Google Scholar 

  30. Magera JS Jr, Frank I, Lohse CM, Leibovich BC, Cheville JC, Blute ML (2008) Analysis of repeat nephron sparing surgery as a treatment option in patients with a solid mass in a renal remnant. J Urol 179(3):853–856

    Article  PubMed  Google Scholar 

  31. Bratslavsky G, Liu JJ, Johnson AD, Sudarshan S, Choyke PL, Linehan WM, Pinto PA (2008) Salvage partial nephrectomy for hereditary renal cancer: feasibility and outcomes. J Urol 179(1):67–70

    Article  PubMed  Google Scholar 

  32. Choyke PL, Glenn GM, Walther MM, Zbar B, Weiss GH, Alexander RB, Hayes WS, Long JP, Thakore KN, Linehan WM (1992) The natural history of renal lesions in von Hippel-Lindau disease: a serial CT study in 28 patients. AJR Am J Roentgenol 159(6):1229–1234

    PubMed  CAS  Google Scholar 

  33. Pahernik S, Ziegler S, Roos F, Melchior SW, Thuroff JW (2007) Small renal tumors: correlation of clinical and pathological features with tumor size. J Urol 178(2):414–417 (discussion 416–417)

    Google Scholar 

  34. Remzi M, Ozsoy M, Klingler HC, Susani M, Waldert M, Seitz C, Schmidbauer J, Marberger M (2006) Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter. J Urol 176(3):896–899

    Article  PubMed  Google Scholar 

  35. Jilg CA, Neumann HP, Gläsker S, Schäfer O, Ardelt PU, Schwardt M, Schultze-Seemann W (2012) Growth Kinetics in Von Hippel-Lindau-associated renal cell carcinoma. Urol Int 88(1):71–78

    Google Scholar 

  36. Steinbach F, Novick AC, Zincke H, Miller DP, Williams RD, Lund G, Skinner DG, Esrig D, Richie JP, de Kernion JB et al (1995) Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study. J Urol 153(6):1812–1816

    Article  PubMed  CAS  Google Scholar 

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Jilg, C.A., Neumann, H.P.H., Gläsker, S. et al. Nephron sparing surgery in von Hippel-Lindau associated renal cell carcinoma; clinicopathological long-term follow-up. Familial Cancer 11, 387–394 (2012). https://doi.org/10.1007/s10689-012-9525-7

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