Hervé Baumert

Recommandations en Onco-Urologie 2010 : Cancer du rein

Il s’agit d’une maladie a transmission autosomique dominante, a forte penetrance (95 % a 60 ans), pour laquelle un seul gene est en cause : le gene VHL situe sur le bras court du chromosome 3 (3p25-p26) (Tableau 1) [1]. La mutation causale du gene VHL est identifiable chez presque tous les patients atteints de cette affection. Il s’agit le plus souvent de mutations ponctuelles (75 % des cas) portant sur la sequence codante, mais des microdeletions, des micro-insertions, des deletions etendues ou une hypermethylation le plus souvent du promoteur ont egalement ete observees. Plus de 150 mutations differentes ont ete repertoriees sur l’ensemble des 3 exons [3-4]. Une consultation d’oncogenetique et un typage genetique du ou des sujets atteints puis des membres de la famille permet la mise en evidence de mutations du gene VHL et l’identification des sujets predisposes a cette maladie (Niveau de preuve 1). Il est recommande de depister les enfants a partir de 5 ans. Une imagerie abdominale annuelle est souhaitable car il existe un risque de 2,7 % de decouverte par an de nouvelle lesion renale (Niveau de preuve 4) [5-6].

Protection of autotransplanted pig kidneys from ischemia-reperfusion injury by polyethylene glycol

Background. Ischemia-reperfusion injury (IRI) is often responsible for graft rejection and leads to delayed graft function of cadaveric kidneys. We have shown that adding polyethylene glycol (PEG 20M) to the preservation solutions helps protect isolated perfused pig kidneys against cold ischemia and reperfusion injury. Methods. We compared the effects of adding PEG to a simplified high-K+ perfusion solution of cold-stored kidneys to Euro-Collins or University of Wisconsin solutions on the function of reperfused autotransplanted pig kidneys. The left kidney was cold-flushed with the preservation solutions and stored for 48 hr at 4°C before reimplantation. Creatinine clearance and fractional excretion of sodium were analyzed 2 days before surgery and over 7 days after transplantation. Histological sections were obtained 40 min after reperfusion and on day 7 after surgery. Results. Adding PEG to the perfusate significantly reduced IRI from autotransplanted pig kidneys. Creatinine clearance was significantly higher and fractional excretion of sodium was significantly lower in pigs transplanted with kidneys cold-flushed with PEG-supplemented perfusate than in those flushed with Euro-Collins or University of Wisconsin solutions. PEG supplementation also better preserved the integrity of kidney cells and markedly reduced interstitial cell infiltrates. Conclusion. PEG protects against IRI and reduces early cellular inflammation. PEG may impair the recruitment and migration of leukocytes into retransplanted pig kidneys. Cold preservation of donor organs with PEG-supplemented solutions may therefore help limit IRI in human renal transplantation.

Citrate, acetate and renal medullary osmolyte excretion in urine as predictor of renal changes after cold ischaemia and transplantation.

Abstract In organ transplantation, the determination of reliable parameters to assess ischaemic damage is essential to predict renal injury after preservation. The aim of this study was to assess renal medullary injury by 1H NMR (proton nuclear magnetic resonance) spectroscopy after preservation and reperfusion. Three experimental groups of pigs were examined during a 2-week period: control group (n = 4), Euro-Collins group (EC) (cold flushed and 48 h cold storage of kidney in EC and autotransplantation, n = 7), and University of Wisconsin (UW) group (cold flushed and 48 h cold storage of kidney in UW and autotransplantation, n = 7). Creatinine and urea were improved in the two cold stored groups. The most relevant resonances determined by 1H NMR spectroscopy after transplantation were those arising from citrate and acetate in urine and trimethylamine-N-oxide (TMAO) in urine and plasma. We demonstrate that graft dysfunction is associated with damage to the renal medulla as determined by TMAO release in urine and plasma. Conversely, citrate excretion can discriminate kidneys with favourable outcome. This study outlines the specific and beneficial impact of UW solution on renal preservation and suggests that 1H NMR spectroscopy is efficient both to detect ischaemic damage of preserved kidneys and to discriminate the preservation quality between different preservation solutions.

Renoprotective effects of trimetazidine against ischemia-reperfusion injury and cold storage preservation: a preliminary study.

BACKGROUND Initial ischemia-reperfusion injury is associated with organ retrieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction. We have recently shown that the protective agent trimetazidine (TMZ) added to preservation solutions: Euro-collins (EC) and University of Wisconsin (UW) was efficient to protect kidneys from ischemia-reperfusion injury in an isolated perfused kidney model. We extended these observations to investigate the role of this drug in the development and progression of organ dysfunction in the autotransplant pig kidney model. METHODS Five experimental groups were studied. After 48-hr cold preservation, autotransplantation and immediate controlateral nephrectomy was then performed in group EC (EC+placebo (n=8), EC+TMZ (n=8), UW+placebo (n=7), and (UW+TMZ) (n=7) and compared with control group (uninephrectomized, n=4) during 14 days. Blood and urine samples were collected for the measurement of creatinine and blood urea nitrogen on postoperative days 1, 3, 5, 7, 11, and 14. Histological analysis was performed after reperfusion and at day 14. RESULTS Survivals were 100% in group B and D versus 42% in group A and 57% in group C. Urine production occurred earlier after autotransplantation from TMZ preserved kidneys than in placebo preserved groups. Peak creat and blood urea nitrogen was significantly greater in groups B and D than in groups A and C. TMZ was also efficient both to reduce ischemia-reperfusion injury and to decrease cellular infiltration. CONCLUSION These results support the beneficial effect of TMZ against ischemia-reperfusion injury and its early effects on grafts in the form of delayed graft function and decreased graft survival. In addition, TMZ reduces inflammatory cellular infiltration in the renal parenchyma.

Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors

Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases. Only 1 metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only 2 cases that showed gain of chromosome 10 as well as loss of chromosomes 9, 11q, and X. The present work studied the genomic characteristics of 2 additional cases of JGCT by comparative genomic hybridization. Similarly to the 2 previously reported cases, these 2 tumors showed loss of chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, 1 case showed gain and loss of entire chromosomes, similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential and then necessitates a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity.

Evidence for a mitochondrial impact of trimetazidine during cold ischemia and reperfusion.

In organ transplantation, ischemia-reperfusion injury (IRI) has been implicated in delayed graft function (DGF) as well as in short- and long-term complications. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na+ version of UW (HEH) or Celsior (CEL) a newly developed high-Na+ solution, with or without trimetazidine (TMZ). Kidney function was better preserved in CEL, UW and particularly HEH in combination with TMZ, particularly after 48 and 72 h. Mitochondria integrity was improved in TMZ-preserved groups. This study indicates that TMZ is efficiently protective against IRI even after prolonged preservation and in different preservation solutions.

Impact of Learning Curve in Laparoscopic Radical Prostatectomy on Margin Status: Prospective Study of First 100 Procedures Performed by One Surgeon

PURPOSE To describe the experience of a single surgeon with his first 100 laparoscopic radical prostatectomies and determine the impact of the learning curve on the surgical margin status according to the rate of nervesparing procedures. PATIENTS AND METHODS Between December 2000 and April 2002, 100 laparoscopic radical prostatectomies were performed by one surgeon without any selection of patients and without the help of any other surgeon. The procedures were divided in four groups of 25 consecutive cases. There was no significant difference among the groups in terms of age, clinical and pathological stage, or Gleason score. Nerve-sparing (NS) dissection was performed when the procedure was easy. Positive surgical margins (SM+) were measured and classified according to their location. RESULTS The overall rate of SM+ was 12.8% in pT2 and 31.8% in pT3 tumors. The SM+ rate was not significantly different among the groups. In contrast, the number of NS dissections (49 patients) increased from group 1 to group 4. Both the positive margin length and the rate of multiple positive margins were significantly lower in the 50 most recent patients. CONCLUSION Nerve-sparing surgery was performed with increasing frequency during this learning curve without compromising the surgical margins. The results suggest that experience could lead to a decrease of both the positive margin length and the rate of multiple positive margins. The impact on cancer control and potency is under evaluation.

National prospective study on the use of local haemostatic agents during partial nephrectomy

To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs).

Off-Clamp versus On-Clamp Robotic Partial Nephrectomy: A Multicenter Match-Paired Case-Control Study

Introduction: The aim of this study was to compare the outcomes of on-clamp and off-clamp robotic partial nephrectomy (RPN). Materials and Methods: The charts of all patients who underwent an RPN at 8 institutions between 2010 and 2014 were retrospectively reviewed. The patients who underwent an off-clamp RPN were matched to on-clamp RPN in a 1-4 fashion according to the following variables: RENAL score, tumor size and surgeons experience. Pre-, intra-, and postoperative data were compared between both groups. Results: Among 525 RPN, 26 were performed off-clamp (5%). They were matched to 104 on-clamp RPN. The complications rate (15.5 vs. 7.7%, p = 0.53), major complications rate (4.9 vs. 3.9%; p = 0.82), and transfusions rate (0 vs. 4.9%; p = 0.58) did not differ significantly between the clamped and unclamped groups. Conversely, estimated blood loss was higher in the off-clamp group (266.4 vs. 284.6 mL, p = 0.048) and so was the rate of conversion to radical nephrectomy (0 vs. 7.7%, p = 0.04). Postoperative preservation of renal function was comparable in both groups. Conclusion: Off-clamp RPN is feasible for a small subgroup of renal tumors without increased risk of postoperative complications but at the cost of higher estimated blood loss and increased risk of conversion to radical nephrectomy.

Familial Ureteral Duplication and Ureterocele: Two Sisters and Their Father

We studied a family in which the father and his two daughters had ureteroceles involving the upper half of a duplex system. Our report gives additional evidence for the genetic background of ureteroceles.