Pediatric Anesthesia 2006 16: 504–513 doi:10.1111/j.1460-9592.2006.01866.

Review article
Anesthetic considerations in the management
of Wilms’ tumor
SIMON D. WHYTE MBBS FRCA A N D J. M A R K A N S E R M I N O
FFA(SA) MMED (ANAES) MSc FRCPC
Department of Pediatric Anesthesia, British Columbia’s Children’s Hospital, Oak Street,
Vancouver, BC, Canada

Keywords: Anesthesia; nephroblastoma; Wilms’ tumor

cases per year are expected in the US; 90% of cases

Introduction
occur before the age of 8 years, with a mean age at
Max Wilms, a German anatomist and surgeon, presentation of 3.5 years. Overall cure rates exceed
described a series of seven cases of nephroblastoma 85% with modern multimodal treatment strategies,
in 1899 (1). Although not the first to do so, his name with prognosis being determined by clinical staging
has become eponymous with the malignancy. Just and histological characteristics of the tumor. Current
over a century later, the management of patients clinical research is focused on minimizing the long-
with Wilms’ tumor has developed into a multidis- term sequelae of treatment in those with excellent
ciplinary undertaking by surgeons, oncologists and prognosis, and on evaluating novel treatment
pathologists, guided by the results of a series of strategies for the small group with poor outcome.
national clinical trials in the US [National Wilms’
Tumor Study Group (NWTSG)], France [Société
Etiology
Internationale d’Oncologie Pédiatrique (SIOP)], the
UK [UK Children’s Cancer Study Group Three disease groups describe the epidemiology of
(UKCCSG)], Germany, and Brazil. Anesthetists Wilms’ tumor: sporadic, familial, and genetic syn-
become involved in the care of these patients during dromes. The majority of these tumors occur sporad-
imaging studies, primary or delayed surgical resec- ically. Familial Wilms’ tumors account for only 1.5%
tion, and management of central venous access for of the total and are associated with mutations at one
chemotherapy administration. This review aims to of two loci (FWT-1 on 17q and FWT-2 on 19q) (3).
provide an overview of current management of Approximately, 10% of Wilms’ tumors occur in
nephroblastoma and to address anesthesia implica- those with syndromic associations. This group rep-
tions of the disease and its treatment. resents a higher risk group, in whom active surveil-
lance is warranted. Associated syndromes are of two
types: overgrowth and nonovergrowth (Table 1).
Overview of Wilms’ tumor
The Wilms’ tumor 1 (WT-1) gene at 11p13 has a clear
Nephroblastoma is the commonest renal neoplasm role in tumorigenesis in the Denys–Drash and
affecting children (2). With an overall incidence of WAGR (Wilms’ tumor, Aniridia, Genitourinary mal-
0.8 per 100 000, it represents approximately 6% of all formations and mental Retardation) syndromes,
pediatric oncological disease. About 500–600 new whilst the WT-2 gene candidate, which maps to
11p15.5, is implicated in the etiology of nephroblas-
Correspondence to: Simon D. Whyte, Department of Pediatric tomas associated with Beckwith–Wiedemann syn-
Anesthesia, British Columbia’s Children’s Hospital, 4480 Oak
Street, Vancouver, BC, V6H 3V4, Canada (email: sdwhyte@ drome. Mutations in WT-1 or the presumed WT-2
bigfoot.com). locus rarely appear in sporadic Wilms’ tumor cells.
Ó 2006 The Authors
504 Journal compilation Ó 2006 Blackwell Publishing Ltd
 WILMS’ TUMOR 5 05

Table 1 is sensitive in identifying nephrogenic rests in the

Genetic syndromes predisposing to Wilms’ tumor
contralateral kidney (6). These foci of embryonic
Overgrowth syndromes kidney precursor cells are potentially premalignant
Beckwith–Wiedemann (10–20% incidence of Wilms’ tumor) and, although most remain dormant or spontane-
Isolated hemihypertrophy (3–5% incidence of Wilms’ tumor)
Soto’s (cerebral gigantism)
ously involute, about 5% will progress to become
Perlman’s (gigantism with renal dysplasia) nephroblastomas. If nephrogenic rests are identified
Simpson–Golabi–Behemel (phenotypically similar to in a kidney resected for a nephroblastoma, regular
Beckwith–Wiedemann)
ultrasound screening for tumor development in the
Nonovergrowth syndromes
Congenital aniridia contralateral kidney is indicated, with the risk being
Denys–Drash (pseudohermaphroditism, glomerulopathy; highest in children under 12 months of age (7).
95% incidence of Wilms’ tumor) The NWTSG recommends formal surgical staging
WAGR (Wilms’ tumor, aniridia, genitourinary malformations,
and mental retardation) in all cases (Table 2). Staging, combined with
Trisomy 18 histological information from primary resection or
biopsy, determines subsequent management.
NWTSG recommends that preoperative chemother-
apy should only precede resection when there are
Clinical Features
bilateral synchronous tumors (5% of all presenta-
The clinical presentation of nephroblastoma is non- tions; commoner in syndromic presentations), unre-
specific, with an asymptomatic abdominal mass sectable tumor, or proximal IVC or atrial extension;
being the commonest feature. Various combinations in all other cases, the initial treatment should be
of abdominal pain, anorexia, nausea, and vomiting primary resection. Postoperative surgical complica-
are present in 30–40%. Signs of associated syndro- tions occur in 20% of all resections (8), but the rate
mic features, such as aniridia, hemihypertrophy, or rises to 40% in those with tumor thrombus that
genitourinary malformations may be apparent on extends up the IVC to or beyond the hepatic veins
examination and, of importance to anesthetists, (9). SIOP advocates preoperative chemotherapy for
hypertension is present in over 50% of cases. The all patients, following image-based staging. The
potential for coagulopathy, due to acquired von argued main benefit is a reduction in tumor size at
Willebrand’s disease, occurs in <10% of cases. the delayed resection and hence fewer surgical
Hematuria is detectable in 30% of patients at complications, including tumor spillage, which can
presentation. alter staging and hence subsequent treatment assign-
ment. However, opponents of the SIOP approach
Diagnosis and Staging
Initial imaging usually consists of ultrasound and
computed tomography (CT) of the abdomen. Ultra- Table 2
Staging of Wilms’ tumor (as applied in NWTS-5)
sound defines the mass as renal or otherwise and
may indicate the presence of renal vein and inferior Stage I Tumor confined to kidney and completely resected;
vena cava (IVC) tumor thrombus. The contralateral no capsular breach, tumor spillage, or renal sinus
extension
kidney and the liver are assessed for metastases. CT Stage II Extracapsular penetration (including iatrogenic via
scanning differentiates renal and adrenal (neurobla- biopsy before removal) or renal sinus extension or
stoma) masses, and provides more detail on the size local spillage during resection; complete resection
with no lymph node involvement
of lymph nodes and the presence of dissemination to Stage III Nonhematogenous spread beyond the kidney
the contralateral kidney or the liver. Chest CT may [abdominal lymph nodes, transected renal vein or
reveal asymptomatic pulmonary metastases that inferior vena cava tumor thrombus];
macroscopic or microscopic residual tumor after
may or may not be apparent on a baseline chest X
resection; peritoneal surface spillage during resection
ray; a controversy currently exists as to whether Stage IV Hematogenous metastases or extra-abdominal lymph
pulmonary metastases detected only by CT should node spread
influence clinical staging of disease (4,5). The role of Stage V Bilateral synchronous Wilms’ tumors – each should be
biopsied and staged independently
magnetic resonance imaging (MRI) is evolving, as it
Ó 2006 The Authors
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5 06 S . D . W H Y T E A N D J. M . A N S E R M I N O

cite a 5% risk of treating benign disease with Table 3

National Wilms’ Tumor Study Group (NWTSG) postresection
chemotherapy, although most SIOP centers now
management of Wilms’ tumor
perform a percutaneous, image-guided fine-needle
confirmatory biopsy to minimize this risk. Moreover, Stage I (all) 18 weeks vincristine,
Stage II FH actinomycin D
chemotherapy may alter the histological classifica-
tion of the tumor, on which subsequent management Stage II UH/FA 24 weeks vincristine, actinomycin D
Stage III FH and UH/FA and doxorubicin
is based. The origins and scientific justifications for Stage IV FH and UH/FA Abdominal/flank DXT ± whole
these divergent management strategies are summar- lung DXTa
ized by D’Angio (10). Stage II-IV UH/DA 24 weeks vincristine, doxorubicin,
Biopsy or resection specimens are sent for histo- cyclophosphamide, and etoposide
pathological examination. Prognostically significant Abdominal/flank DXT ± whole
lung DXTa
differentiation is made between tumors with favo-
rable and unfavorable histology. Wilms’ tumors a
Whole lung radiotherapy (DXT) for stage IV disease with
arise from embryonal metanephric blastemal cells pulmonary metastases visible on initial chest X ray. The value of
whole lung irradiation for pulmonary metastases detected only on
that normally differentiate into one of three mature computed tomography (CT) is undetermined.
constituent renal tissue cells – blastemal, stromal, FH, favorable histology; UH/FA, unfavorable histology with focal
and epithelial. Wilms’ tumors with favorable histo- anaplasia; UH/DA, unfavorable histology with diffuse anaplasia;
DXT, radiotherapy.
logy typically consist of a variable mixture of all
three cells types (triphasic), although biphasic and
monophasic variants are seen. Occasionally, other but the risk of renal failure is much higher in
epithelial or stromal precursor tissues may be this group. In an attempt to facilitate nephron-
present, e.g. mucinous cells, epithelial, cartilaginous sparing surgery, management involves initial
or muscular tissue, osteoid, or fat (teratoid Wilms’ staging surgery with biopsy of both masses,
tumors). Wilms’ tumors with unfavorable histology followed by 6–8 weeks of prenephrectomy chemo-
feature anaplastic cells. Anaplasia is apparent in 5% therapy to shrink the tumors’ size. A second
of tumors, more commonly from older patients. A surgical evaluation is then performed. In some
prognostically relevant distinction, defined by for- cases, the tumor in one kidney will have regressed
mal criteria, has been identified between tumors completely, permitting a unilateral delayed radical
with focal and diffuse anaplasia. nephrectomy of the persistently affected kidney. In
In summary, after clinical diagnosis and imaging other cases, both tumors are still present, but
studies, most patients undergo surgical staging and, smaller, and bilateral partial nephrectomies may be
if possible, primary radical nephrectomy. Patients undertaken. In some cases, after the second eval-
with bilateral disease, proximal IVC/atrial extension uation, further chemotherapy or radiotherapy may
or unresectable tumors are biopsied before receiving be needed, but surgical resection cannot be
prenephrectomy chemotherapy for 6–8 weeks, delayed indefinitely, as this introduces the risk of
whereafter they are reassessed surgically and under- clonal expansion of chemo- and radiotherapy-
go delayed nephrectomy (or partial bilateral neph- resistant tumor cells.
rectomy if residual bilateral disease). Further
management is dictated by staging and histology
Metachronous disease
(Table 3). If an SIOP protocol is followed, image-
based staging, then preresection chemotherapy fol- A second Wilms’ tumor may develop in the remain-
lowed by a delayed nephrectomy, is the initial ing kidney in 1–3% of children successfully treated
sequence of treatment. for unilateral Wilms’ tumor. The risk of this bilateral
metachronous Wilms’ tumor is higher when the
initial presentation is under 12 months of age and
Bilateral disease
when the first resected kidney contains nephrogenic
Synchronous bilateral Wilms’ tumors (stage V) are rests (7). Such patients should undergo regular
found in about 6% of children who present with abdominal ultrasound screening for metachronous
nephroblastoma. Stage V survival exceeds 70%, tumor development.
Ó 2006 The Authors
Journal compilation Ó 2006 Blackwell Publishing Ltd, Pediatric Anesthesia, 16, 504–513
 WILMS’ TUMOR 5 07

elucidated and the chest X ray reviewed. A baseline

Relapsed disease
blood pressure reading is mandatory. The anesthet-
Relapsed Wilms’ tumors are associated with a ist should review a recent full blood count (anemia
poorer prognosis. Salvage multiagent chemotherapy may have resulted from occult hematuria) and
with combinations of cyclophosphamide, ifosfa- electrolytes. In most cases, renal function is normal.
mide, etoposide, and carboplatin has contributed to In the cases of syndromic Wilms’ tumor, it is
the improved survival rates of 50–60% in this group. essential to review the syndrome’s features for any
Predictors of better outcome include relapse more anesthesia implications. Published experience of
than 6 months after an initial diagnosis, stage I and anesthesia in patients with some of these syndromes
II disease, favorable histology, and no prior radio- is inevitably limited and, in some instances, absent.
therapy or doxorubicin therapy. Of the overgrowth syndromes, Beckwith–Wied-
emann and Simpson–Golabi–Behemel syndromes
both feature macroglossia, hypotonia, and hyperin-
Anesthesia Considerations
sulinism whilst Soto’s syndrome is associated with
The challenges of anesthetizing pediatric patients congenital heart disease (11) and marked hypotonia.
with Wilms’ tumor are primarily those pertaining to Children with overgrowth syndromes may require
lengthy transabdominal retroperitoneal surgery in airway equipment of a size that is different to that
small children and infants: thermoregulation, fluid usually predicted by age or weight. Of the nonover-
balance, ventilation with raised intra-abdominal growth syndromes, patients with Denys–Drash syn-
pressure, intermittent IVC compression, and poten- drome develop early renal impairment and
tial for major hemorrhage. In addition to these secondary hypertension, whilst those with trisomy
‘routine’ issues may be the consequences of para- 18 (Edward’s syndrome) have multiple anomalies,
neoplastic phenomena, such as hypertension and including micrognathia.
coagulopathy, of proximal IVC or atrial extension of At the preoperative visit prior to nephrectomy, in
tumor thrombus, and of preoperative or previous addition to the standard enquiries and investiga-
treatment with chemotherapeutic drugs. tions discussed above, a coagulation profile should
be reviewed and a check made that cross-matched
blood will be available at the time of surgery. The
Preoperative evaluation
anesthetist should ensure that the presence and
Children with Wilms’ tumor present for anesthesia extent of any IVC thrombus has been established by
assessment at various stages of their long-term CT angiography or echocardiography, as even atrial
management, and assessment will necessarily de- tumor thrombus may be asymptomatic. Some chil-
pend upon the procedure to be performed and the dren will have received prenephrectomy chemo-
patient’s clinical condition. The majority of children therapy. Initial chemotherapy regimens include
with untreated Wilms’ tumor are asymptomatic and actinomycin D, which may impair hepatic and
systemically well. Depending on age, they may hemopoietic function, increasing the risk of coagulo-
require anesthesia for imaging studies (CT or MRI) pathy; and vincristine, which may cause the syn-
before being scheduled for primary nephrectomy. drome of inappropriate antidiuretic hormone
Insertion of an indwelling venous access device secretion. Children with advanced stage disease also
(VAD) may be undertaken immediately prior to receive doxorubicin. The potential for anthracyclines
surgical staging and resection, or as an isolated to cause myocardial damage, resulting in cardiac
procedure for preresection chemotherapy. dysrhythmias and acute cardiomyopathy, is well
In all cases, standard enquiries should be made recognized. These children should have undergone
regarding previous anesthetics, family history of recent echocardiography to assess myocardial con-
anesthetic problems, current medications, known tractility. Table 4 summarizes the pharmacology and
allergies, and any coexisting medical problems. side effect profiles of agents used in current chemo-
Examination should be directed by information therapy regimens.
elicited from the history. In suspected stage IV The anesthetist should discuss plans for
disease, respiratory symptoms and signs should be perioperative pain management and, if anticipated,
Ó 2006 The Authors
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Table 4
Chemotherapy agents used in the treatment of Wilms’ tumor

Drug Pharmacology Side effects of anesthetic relevance

Vincristine Vinca alkaloid from Vinca rosea (periwinkle). Peripheral neuropathy (reversible)
Binds microtubules of mitotic spindle and Minimal myelosuppression and immuno-suppression
causes metaphase arrest. Hepatic metabolism; SIADH; convulsions; CNS depression (rare)
biliary and fecal excretion. Toxicity enhanced by liver impairment

Actinomycin D Derived from Streptomyces parvullus. Myelosuppression (maximal at 2–3 weeks)

Inhibits DNA-dependent RNA polymerase. Severe diarrhea (maximal at 2–3 days)
Mainly hepatic metabolism. Nausea and vomiting
Immunosuppression
Fulminant hepatic failure in 3.5% when given
in concert with vincristine
Radiosensitizing – increases DXT-induced damage,
especially if DXT is concurrent
Toxicity enhanced by liver impairment

Doxorubicin Anthracycline antibiotic from Streptomyces peucetius. Acute toxicity: myelosuppression (maximal at 1–2 weeks);
Inhibits nucleic acid synthesis, binds DNA thrombocytopenia; cardiac dysrhythmias.
and inhibits topoisomerase II. Hepatic metabolism Radiosensitizing.
(<5% excreted in urine). Toxicity enhanced by hepatic impairment.
Chronic toxicity: decreased cardiac contractility,
progressing to cardiac failure, may be seen above total
cumulative doses of 200 mgÆm2. Reversibility of changes
unknown. Cardiac damage is exacerbated by cardiac
irradiation. Monitor with serial ECGs and ECHO at
baseline, 2–3 weeks after receiving 200 mgÆm2,
and after every further 100 mgÆm2 thereafter.
After completion of therapy, monitor with clinical
assessment and Holter monitoring every 3 years and
at times of increased physiological stress (e.g. pregnancy).
Cyclophosphamide Alkylating agent. Prodrug activated by liver Myelosuppression, maximal at 1–2 weeks
phosphamidases. Exclusive renal extraction. Hemorrhagic cystitis
Nausea and vomiting
Immunosuppression
SIADH
Pulmonary fibrosis (rare)
Myocardial necrosis, dysrhythmias and renal toxicity
at very high doses and short treatment intervals

MESNA Thiol compound. Protects against urotoxicity of Nausea and vomiting

cyclophophamide and ifosfamide.
Etoposide Topoisomerase II inhibitor. Mainly renally extracted. Myelosuppression, maximal at 1–2 weeks
Nausea and vomiting
Anaphylaxis
Carboplatin Binds replicating DNA, causing single strand breaks Myelosuppression, especially thrombocytopenia
and DNA cross-linking. Renal extraction that is Nausea and vomiting
GFR-dependent. Nephrotoxicity (reversible)
Peripheral neuropathy
Hepatotoxicity (uncommon)

DXT, radiotherapy; ECG, electrocardiogram; ECHO, echocardiogram; GFR, glomerular filtration rate; MESNA, sodium-2-mercaptoethane
sulphonate; SIADH, syndrome of inappropriate anti-diuretic hormone secretion.

high-dependency or intensive care unit monitoring, opioid regimens being the main alternative; the risks
as well as postoperative ventilation. We discuss the and benefits of these options need to be presented to
potential need for allogeneic blood transfusion. parents in a way that allows them to make an
Epidural anesthesia is an excellent strategy for informed choice for their child and to feel actively
postoperative analgesia in these patients, with i.v. involved in care decisions.
Ó 2006 The Authors
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 WILMS’ TUMOR 5 09

should always be considered, as it is notoriously

Intraoperative management
easy to underestimate third space fluid loss in
The choice of anesthesia technique should be major pediatric abdominal surgery, and surgical
guided by relevant preoperative evaluation find- bleeding must be excluded.
ings. In the otherwise healthy asymptomatic child
undergoing nephrectomy ± insertion of VAD, i.v.
Postoperative care
or inhalational induction is acceptable. The authors
maintain anesthesia with a balanced technique, High dependency care will be required following
using a remifentanil infusion at 0.15–0.3 lgÆkg)1Æ the resection of most large abdominal masses,
min)1 and isoflurane or desflurane in air/oxygen, particularly when associated with preoperative or
with low flow and a cuffed orotracheal tube. intraoperative hypertension or significant blood loss.
Minimum monitoring standards should be Because of the vascular nature of the dissection, a
observed. Because of the potential for hemodynam- high suspicion of secondary hemorrhage should be
ic instability during tumor handling and the com- maintained. Postoperative ventilation may be re-
mon presence of hypertension, we routinely insert quired in the event of significant pulmonary atelec-
an arterial line. Wide-bore upper limb peripheral tasis due to abdominal retraction, prolonged
venous access is essential; if a VAD is being procedures with significant blood loss, or tumor
inserted before nephrectomy, then this may be used embolization.
for both central venous pressure monitoring and for
volume resuscitation if required. Core temperature
Specific Anesthetic Considerations
monitoring is mandatory, to warn of impending
hypothermia and – especially when forced air Associated conditions that are important to consider
warming techniques are used – hyperthermia. during the perioperative period include intravascu-
Careful positioning, padding of pressure areas, lar extension that may dislodge and cause pulmon-
and eye protection should be standard practice. ary emboli, or extend into the heart itself, creating
Part of the surgical staging process is to inspect significant surgical challenges; hypertension, which
and palpate the contralateral kidney before resect- is present in more than 50% of children and may be
ing the affected one. Both can be achieved by precipitated by tumor handling; coagulopathy due
traversing the peritoneal cavity via a single gener- to acquired von Willebrand’s disease; and poly-
ous transverse supraumbilical incision, and then cythemia due to excessive erythropoietin production
making bilateral incisions in the posterolateral from the tumor.
peritoneal (Gerota’s) fascia to access the retroper-
itoneum on each side. The skin incision and
Intravascular Extension
surgical path will be optimally blocked by an
effective epidural inserted at a low thoracic level, Intravascular extension occurred in 4.1% and 6% of
such as T9/10. patients in NWTS-3 and 4, respectively (9,12). In the
The surgical imperative is to excise the kidney, majority of patients, it is limited to the IVC, with
which is usually grossly enlarged, without ruptur- atrial extension in only 1% of the total. The risks
ing the tumor capsule. Tumor spillage immediately associated with intravascular extension are pulmon-
up-stages stage I disease to stage II or III, which ary embolism, IVC obstruction, and tricuspid valve
may alter subsequent treatment assignment (see obstruction. Intravascular extension is frequently
Table 3). Thus, the surgeons’ focus may not always asymptomatic but may present as a new cardiac
be on the effect of their activities on the patient’s murmur or pulmonary embolus. Preoperative ultra-
venous return. Intraoperative hemodynamic insta- sound or MRI evaluation is recommended to rule
bility may be attributable to several different out intravascular extension. Echocardiography faci-
factors, but most commonly, hypotension is be- litates assessment of valvular and chamber involve-
cause of intermittent mechanical compression of the ment and cardiac function.
IVC by the surgeon during mobilization of the The presence of intravascular extension does not
affected kidney. The possibility of hypovolemia seem to affect ultimate survival (12) and these
Ó 2006 The Authors
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Table 5
Anesthesia considerations with intravascular extension of Wilms’ tumor

Consideration Notes

Extent of intravascular extension Hepatic venous congestion, hepatic dysfunction and ascites may be
present if hepatic venous drainage is impaired.
If atrial extension, is there any Pleural effusions may be present and can affect respiratory reserve.
tricuspid valve obstruction?
Prenephrectomy chemotherapy Check preoperative tests of hepatic, coagulation, and cardiac function
Surgical plan Will cardiopulmonary bypass (CPB) be needed?
Intravenous access Potential for extensive hemorrhage and the need to intermittently clamp
the IVC. Place large bore IV access in the upper limbs.
CVP monitoring Desirable because of potential for intraoperative embolization. However,
the benefit of siting the line must be weighed against the risk of dislodging
fragments of tumor. A surgical venous access device (VAD) may already
have been inserted for chemotherapy. Any percutaneous approach should be
ultrasound-guided and the location of catheters should, where necessary,
take into consideration the anticipated positioning of venous cannulae for CPB.
Epidural placement The IVC obstruction results in expansion of retroperitoneal venous collaterals to conduct
lower body venous return. Such collaterals communicate with epidural venous plexuses,
so the risk of inserting an epidural catheter may be anticipated to be greater,
especially if full heparinization is planned for CPB.
Transesophageal echocardiography May be appropriate for establishing the presence of flow across a persistent
foramen ovale or atrial septal defect, and for monitoring for emboli during those
parts of the procedure in which the IVC is being manipulated in non-CPB approaches.

patients are therefore treated aggressively. Initial A number of surgical approaches have been
management is somewhat controversial; primary described to manage the resection of intravascular
surgical tumor resection in the presence of intravas- tumor thrombus. Infrahepatic extension only can
cular extension is associated with an increased usually be extracted via the abdominal incision, by
incidence of surgical complications (odds ratio 2.2), controlling the proximal and distal IVC. Supra-
the most common being intestinal obstruction and hepatic extension and beyond requires mobilization
extensive hemorrhage. Complications are greater in of the liver and control of hepatic venous return,
those with atrial rather than just caval extension. For whilst atrial thrombectomy is usually resected with
these reasons, prenephrectomy chemotherapy is the aid of CPB, to reduce the likelihood of tumor
usually recommended, as it reduces the surgical embolization. Viable tumor is still present in 50% of
complication rate and causes significant regression thrombus resected after chemotherapy. In the pres-
of atrial extension, reducing the need for cardiopul- ence of persistent intracardiac extension, simulta-
monary bypass (CPB). It may, however, increase the neous intra-abdominal and intracardiac resection
preoperative complication rate, increase adherence has been successfully performed using the partial
of the tumor to the IVC and prevent accurate CPB (13). Resections under mild hypothermic CPB
histological staging. In a retrospective review of without cardioplegia and under full CPB with deep
165 patients with intravascular extension enrolled hypothermic circulatory arrest (DHCA) have been
within NWTS-4, the incidence of surgical complica- advocated, with each technique having advantages
tions was 26% in the primary surgery group (25/96) and disadvantages (14,15). The presence of a per-
vs 13% in the prenephrectomy chemotherapy group sistent intra-atrial communication may necessitate
(8/68), a difference that was marginally significant. deep hypothermic arrest, in order to prevent pul-
However, five patients sustained complications monary venous return to the left atrium flooding the
whilst on presurgery chemotherapy, one of which surgical field.
was a fatal pulmonary embolus, so the incidence of Specific anesthetic considerations for the child
all complications between the two groups (26% vs with intravascular extension of Wilms’ tumor are
18.8%) was not statistically different (9). summarized in Table 5.
Ó 2006 The Authors
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 WILMS’ TUMOR 5 11

Paraneoplastic phenomena labetalol, hydralazine, diazoxide, and prazosin

(23,28,30) have not been effective in the control of
Hypertension preoperative blood pressure. Diuretics, unsurpris-
The association between hypertension and Wilms’ ingly, do not affect the mechanism of hypertension
tumor was first described in 1938 (16). The incidence in these patients, and may worsen electrolyte
of hypertension in children presenting for surgical disturbances. Phenoxybenzamine, phentolamine,
resection of Wilms’ tumor is in excess of 50% (17). and sodium nitroprusside have been used for
Hypertension can be the presenting feature (18), intraoperative control of blood pressure (19).
may be associated with polydipsia, and may lead to Labile perioperative blood pressure, particularly
critical cardiovascular decompensation (19). Hyper- during tumor handling, is a potential risk and
tension may have a higher association with tumors justifies invasive monitoring of blood pressure.
of a more favorable histological diagnosis. However, the incidences of perioperative hyperten-
Wilms’ tumor is often associated with increased sive or hypotensive episodes related to fluctuating
plasma concentrations of renin (20–23), but not all renin concentrations are rare with adequate preop-
patients are hypertensive (22,24) as it may be erative control of blood pressure (17). Although
inactive (prorenin form) in some patients (25,26). renin levels fall to normal within hours of resection,
The renin is produced by areas of the kidney cortex blood pressure may take up to a month to normalize,
entrapped within the tumor and perivascular spaces reflecting gradual resolution of arteriolar medial and
external to the tumor (22,23,27). Renin, normally left ventricular hypertrophy. Antihypertensive treat-
produced by the juxtaglomerular apparatus, acts on ment can usually be discontinued within 1–3 weeks
circulating angiotensinogen to produce angiotensin of resection.
I. Angiotensin II, a potent arteriolar vasoconstrictor,
is produced by the conversion of angiotensin I,
Coagulopathy
mainly in the lungs. Angiotensin II is also dipso-
genic, which explains the polydipsia described in A minority (under 10%) of patients with Wilms’
some case reports. Hypertension associated with tumor have acquired von Willebrand’s disease. Von
nephroblastoma may be labile and may be severe. Willebrand’s factor is a plasma protein that is
Intravascular volume contraction and left ventric- integral to the platelet adhesion mechanism and to
ular hypertrophy may result from sustained hyper- the function of factor VIII in the clotting cascade.
tension. In this respect, there are clinical parallels Von Willebrand’s disease is therefore characterized
with neuroblastoma and pheochromocytoma, and by both platelet dysfunction and coagulopathy.
similar perioperative preparations may be necessary. Bleeding time is prolonged and platelet aggregation
In addition, electrolyte disturbances may result from in the presence of ristocetin is abnormal. Given the
polydipsia and from aldosterone-induced renal potential for surgical hemorrhage and the consider-
potassium wasting. ations of epidural anesthesia, it seems prudent to
The angiotensin-converting enzyme (ACE) inhib- check platelet function preoperatively. Perioperative
itors, particularly captopril, are effective in treating cryoprecipitate should be available to correct any
the hypertension (28). Saralasin (29), a synthetic detected deficit.
angiotensin II analog, has been used to control
severe hypertension in Wilms’ tumor. Beta-adrener-
Polycythemia
gic blockade should be used with caution in patients
with uncontrolled hypertension, as the beta blockade With only 10 cases reported, polycythemia is a rare,
is unlikely to affect the mechanism of the hyperten- but occasionally the presenting (31), manifestation of
sion and may exacerbate the hypertension by inhib- Wilms’ tumor. It is associated with male gender,
iting the beta-adrenergic vasodilatory mechanism. older age, and favorable clinical stage (32). The
Adrenergic blockade may also reduce the compen- majority of patients show an elevated serum ery-
satory increase in cardiac output required during the thropoietin level, although polycythemia can occur
labile perioperative period. Various combinations of in the presence of an apparently normal serum

Ó 2006 The Authors

Journal compilation Ó 2006 Blackwell Publishing Ltd, Pediatric Anesthesia, 16, 504–513
5 12 S . D . W H Y T E A N D J. M . A N S E R M I N O

erythropoietin. The physiological range of serum

Acknowledgements
erythropoietin is wide (5–30 mIUÆmlÆ)1) and shows
interindividual variation. This means that polycy- We thank Drs Carolyne Montgomery, Stephan Mal-
themic patients with seemingly normal erythropoie- herbe (Department of Pediatric Anesthesia), Dr Erik
tin levels may in fact have levels that are high for Skarsgard (Department of Pediatric Surgery), and
them, yet within the population’s absolute normal Dr Paul Rogers, (Department of Pediatric Oncology)
range. Furthermore, autonomous secretion may be for their input to the manuscript.
episodic; serum half-life is only 1.5–3 h, so sampling
times may miss serum peaks (32).
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 WILMS’ TUMOR 5 13

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Accepted 1 December 2005
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Ó 2006 The Authors

Journal compilation Ó 2006 Blackwell Publishing Ltd, Pediatric Anesthesia, 16, 504–513