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Prof. Denis A. Cozzi
Chirurgia nephron-sparing per tumorirenali primitivi in età pediatrica.
Università di Roma “La Sapienza”U.O.C. Chirurgia Pediatrica - Policlinico Umberto I
Direttore: Prof Francesco Cozzi
Clinical and experimental data suggest that hyperfiltrationfollowing removal of a critical mass of renal tissue causes a progressive glomerular damage.
Background
Anderson KD et al. J Urol, 1985
Patients with a reduction of renalmass of more than 50% are at increased risk of renal failure.
Background (cont.)
Novick et al. N Engl J Med, 1991
Aim of the study
To evaluate the feasibility and safety of nephron-sparing surgery (NSS) in childrenwith syncronous bilateral Wilms’ tumour(BWT).
NWTS-1 (1969-’73)
NWTS-2/3 (1974-’86)
NWTS-4 (1986-’94)
UKCCS (1980-’95)
SIOP/Ger (1994 /’01)
Studies No. of Patients
PreoperativeChemotherapy (%)
30
185
98
71
89
10
41
70
81
100
Results of treatment for bilateral Wilms’ tumor
Cozzi DA and Zani A. Seminars Ped Surg, 2006
NWTS-1 (1969-’73)
NWTS-2/3 (1974-’86)
NWTS-4 (1986-’94)
UKCCS (1980-’95)
SIOP/Ger (1994 /’01)
Studies No. of Patients
No. of kidneys receiving NSS (%)
30
185
98
71
89
23
51
72
42
76
Results of treatment for bilateral Wilms’ tumor
Cozzi DA and Zani A. Seminars Ped Surg, 2006
NWTS-1
NWTS-2 and 3
NWTS-4UKCCS
SIOP/Ger
Overall survival rate (%)
87
83
92-
-
Mean follow-up (years)2 4-5 6-10
-
73
82-
83
-
70
-69
-Cozzi DA and Zani A. Seminars Ped Surg, 2006
Results of treatment for bilateral Wilms’ tumor
NWTS-1 (1969-’73)
NWTS-2/3 (1974-’86)
NWTS-4 (1986-’94)
UKCCS (1980-’95)
SIOP/Ger (1994 /’01)
Studies No. of Patients
NephrectomyNo. patients (%)
30
185
98
71
89
67
83
55
72
45
Results of treatment for bilateral Wilms’ tumor
Cozzi DA and Zani A. Seminars Ped Surg, 2006
In children with syncronous BWT, NSS does not impair the excellentoutcome.
Conclusion
Cozzi DA and Zani A. Seminars Ped Surg, 2006
Conclusion (cont.)
Nearly half of the patients remainwith less than 50% of renalparenchyma.
Cozzi DA and Zani A. Seminars Ped Surg, 2006
A more aggressive NSS approach seems justified.
Implication
Cozzi DA and Zani A. Seminars Ped Surg, 2006
Background
The major emphasis of both the NWTSG and SIOP is reducing the morbidity of treatment for low-risk patients while maintaining the excellent survival rate.
In nephrectomized children, the risk of renal failure due to hyperfiltration is considered low.
Nephron-sparing surgery for children with unilateral renal tumour and normal contralateral kidney is a controversial issue.
Background
Wilms’ tumor : survival rate(SIOP-9: 1987-92)
Months
0%
20%
40%
60%
80%
100%
4 8 12 16 20 24 32 36
I fav.I stand/ana.II N0IIN1+IIIIVunfav.
Adults after partial removal of a solitary kidney
Novick et al. N Engl J Med, 1991
0
1
2
3
Amount of kidney remaining (%) 72 ± 438 ± 16 60 ± 19
Uri
nar
y p
rote
ing/day
p =0.006
Adults after partial removal of a solitary kidney
Novick et al. N Engl J Med, 1991
124 ± 4663 ± 2 81 ± 20
g/day
Uri
nar
y p
rote
in
Follow-up (months)
p =0.0005
0
1
2
3
0
40
80
120
Long-term follow-up of patients undergone unilateral nephrectomy in childhood
p =N.S.
Robitaille et al. Lancet, 1985Interval since nephrectomy (years)
25 - 3317 - 24
Creatinine clearance (ml/min/1.73m2)
Wikstad et al. Pediatr Nephrol, 1988
Adults born with unilateral agenesis or nephrectomized in childhood
150
125
100
75
50
25
026-407-15 16-25
Urinary albumin (µg/1.73m2/min)150
125
100
75
50
25
0
GFR (ml/1.73m2/min)
Follow-up (years)
Longitudinal changes of postoperativeserum creatinine standard deviation scores
1 2 3 4 5 6 7 8 9
-1
0
1
2
Follow-up (years)
Seru
mcr
eatin
ine
SDS
r2=0.49p= 0.02
(Values are Means ± SE)
Cozzi F et al. J Urol, 2005
Cozzi F et al. J Urol, 1996
Enucleative Surgery for Stage I NephroblastomaWith a Normal Contralateral Kidney.
Nephron-Sparing Surgery for Unilateral Primary Renal Tumour in Children.
Cozzi DA et al. J Ped Surg, 2001
Patient characteristics
(January 1992 – August 2006)Unilateral primary renal tumours (37 children)
Nephrectomy Nephron-sparing surgery
All stages Stage I
Event-free Survival 85 % Event-free Survival 100 %
Mean follow-up 8 yrs Mean follow-up 8 yrs
No of patients 26 No of patients 11
Pre-operative Two-drug regimen (SIOP)
Post-operative 1992-1995: Three-drug regimen
1996 - : Two-drug regimen
Nephron-Sparing Surgery Chemotherapy
11No. of patients
Nephron-Sparing Surgery Procedures
No. of tumour enucleation 7
No. of partial nephrectomy 5
0
10
20
30
40
50
DMSA uptake of kidney remnant after NSS
Mean Follow-up15 mos. 5.6 yrs.
Split
rena
lfun
ctio
n(%
)
BAPS Meeting, Dublin 2005
0
10
20
30
40
50
Mean Follow-up15 mos. 5.6 yrs.
p = n.s.
Split
rena
lfun
ctio
n(%
)
DMSA uptake of kidney remnant after NSS
BAPS Meeting, Dublin 2005
0 10 20 30 40 500
10
20
30
40
50
Ultrasound measured renal volume and DMSA measured renal function
Split renal function (%)
Split
rena
lvol
ume
(%)
r2 = 0.81p = 0.002
BAPS Meeting, Dublin 2005
Following NSS, split renal function of the affected kidney remnant is satisfactory, stable, and well correlated with split renal volume.
Conclusion (i)
BAPS Meeting, Dublin 2005
Creatinine (mg/dl) 0.79±0.03 0.63±0.03 0.001
Systolic pressure (mmHg) 112.5±8.6 100.0±9.1 <0.001
Dyastolic pressure (mmHg) 72.5±8.4 63.5±7.1 0.005
p valueNSS(10 patients)
Nephrectomy(16 patients)
Post-surgery interval (months) 71.9±41.9 65.3±38.6 0.35
Renal function and blood pressuremeasurements following surgery
(Values are Means ± SD)
Creatinine SDS 1.27±0.69 0.70±0.49 0.02
Systolic pressure SDS 0.72±0.74 -0.10±0.92 0.01
Dyastolic pressure SDS 0.87±0.77 0.19±0.62 0.01
Cozzi F et al. J Urol, 2005
Ablative renal surgery is followed by a progressive renal dysfunction.
Nephron sparing surgery has a renalfunction advantage over nephrectomy.
Conclusion (ii)
Cozzi F et al. J Urol, 2005
Nephron-sparing surgery in children with unilateral
renal tumour: a systematic literature review.
SIOP Meeting, Geneve 2006
To evaluate the oncological risk of NSS in children with primary renal tumour and normal contralateral kidney.
Aim of the study
Comprehensive review of the Literature:
Methods
Electronic search (MEDLINE, OVID, EMBASE)
Hand-search (reference lists of articles, abstracts from conference proceedings)
37
30
1310
8 7
2 25 5
2 1 1 10
20
40
German
yPor
tugal
Italy
Poland
Austri
a
The N
ether
lands
Switzer
land
Fran
ceUSA
Canad
aNew
Zeland
Austra
liaJa
pan
IndiaPatient per country
No.
of p
atie
nts
Results
Local recurrence 7 (5.6%)
No. of patients 124
Survival rate 95.1 %
Follow-up (mean)
Overall
≅ 4 yrs
Benign or “low-risk” Wilms’tumours
Local recurrence 0
No. of patients 17
Survival rate 100 %
Follow-up (mean) 3.6 yrs
No. of patients
Cystic nephroma 5
Cystic partially differentiated nephroblastoma
7
Congenital mesoblastic nephroma 4
Oncocytoma 1
Benign or “low-risk” Wilms’tumours
Stage I “Intermediate-risk”Wilms’ tumour
Local recurrence 4 (6.6 %)
No. of patients 60
Survival rate 98.3 %
Follow-up (mean) 4 yrs
No. of patients
Hyperplastic nephroblastomatosis 4
Beckwith-Wiedemann syndrome 2
Hemihypertrophy 1
Aniridia, hypospadias, cryptorchidism 1
Patients at increased risk of metachronous Wilms’ tumour
Local recurrence 0
No. of patients 32
Survival rate 94 %
Follow-up -
(no data on staging)“Intermediate-risk” Wilms’ tumour
Local recurrence 3 (20%)
No. of patients 15
Survival rate 80 %
“High-risk” or stage II / III “Intermediate- risk” Wilms’ tumour
Follow-up -
0
20
40
60
80
100
No.
of p
atie
nts
Preoperativechemotherapy
Primarysurgery
NSS for unilateral Wilms’ tumour: pre-op chemotherapy
Intermediate / High-risk WT
Benign / Low-risk WT
0
10
20
30
40
No.
of p
atie
nts
P =0.04
Complete nephrectomy
Partialnephrectomy
Preoperativechemotherapy
Primarysurgery
NSS and pre-op chemotherapy for Wilms’ tumour in horseshoe kidneys
Neville H et al. JPS 2002
In children with benign or “low / intermediate- risk” histology stage I WT and a normal opposite kidney, the oncological risk of NSS is low, probably because histology and staging are related to the biology of the tumour.
Conclusion (iii)
“A prospective trial of less aggressive intervention should be considered for select patients with unilateral WT and normal opposite kidney.”
Implication
Zani A et al. J Urol. 2005 Mar;173(3):946-8; discussion 948
Ross J, Cleveland, Ohio
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