Hyperdynamic Heart Failure Due to A-V Fistula Associated With Wilms' Tumor

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EXPERIENCE

AND

REASON-Briefly

Recorded

“In Medicine one must pay attention not to plausible theorizing but to experience and reason

together. .. .Iagree that theorizing is to be approved, provided that it is based on facts,

and systematically makes its deductions from what isobserved. . ..But conclusions drawn

from unaided reason can hardly be serviceable; only those drawn from observed fact.” Hippocrates: Precepts. (Short communications offactual material are published here. Comments

and crihcis,ms appear as Letters to the Editor.)

Hyperdynamic

Heart Failure Due to A-V

Fistula Associated With Wilms’ Tumor

Intrarenal

arteriovenous

(A-V)

fistula

asso-ciated

with

Wilms’

tumor

is extremely

rare

and

is

an

unusual

cause

of

congestive

heart

failure

in

infancy

and

childhood.

In

a recent

review

of 440

children with Wilms’ tumor, Miller

et al.’

did

not

find

a single

case

of

A-V

fistula;

nor

did

Comes

and

Bernatz2

find

any

Wilms’

tumors

in

139 patients

with

various

forms

of A-V

fistula.

Results

of angiographic

studies

in

children

with

Wilms’

tumor

are

at

marked

variance

as

to

the

occurrence of A-V fistula. Whereas Hidai

et

al.3

and

others”

did

not

find

a single

patient

in whom

Wilms’

tumor

was

associated

with

intrarenal

A-V

fistula,

Cremin

et

al.7

and

Meng

and

Elkin8

reported

such

an association

in two

of 13 and

one

of 6 children,

respectively.

All three

patients

were

asymptomatic.

Finally,

in

the

pediatric

age

group,

there

is only

one

reported

instance

where

intrarenal

A-V

fistula

with

Wilms’

tumor

resulted

in

congestive

heart

failure.”

However,

the

description

of that

case

did

not

include

hemody-namic

changes

associated

with

the

fistula.

Our

purpose

is to report,

in a child,

reversible

hyperdynamic

circulatory

state

and

congestive

heart

failure

due

to

multiple

intrarenal

A-V

fistulas

associated

with

Wilms’

tumor,

to

docu-ment

associated

hemodynamic

alterations,

and

to

briefly

discuss

the

pathogenesis

of

fistula

forma-tion

in such

a patient.

FIG. 1. Retrograde aortogram following injection of contrast material into descending aorta shows: A, right renal artery (black

arrow) larger than the left (open arrow) and abnormal intrarenal A-V communication (black-and-white arrow); B, a film taken 1.5

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CASE

REPORT

TABLE I

EXPERIENCE

AND

REASON

565

J.F., a 31-month-old white boy, was well until he

devel-oped coryza, cough, fever, lethargy, and exertional dyspnea

eight weeks prior to the present illness. A physical examina-lion showed tachypnea, tachycardia, and cardiomegaly. A

presumptive diagnosis of viral myocarditis with congestive

heart failure was made and the patient was admitted to a

local hospital where he was given digitalis and diuretics.

During the next few days he developed microscopic

hema-tuna and radiologic evidence of lung opacities. An

intra-venous pyelogram suggested distortion of the collecting

system of the right kidney. A diagnosis of Wilms’ tumor was

made and the patient was referred to St. Jude Children’s

Research Hospital for further evaluation and management.

A physical examination on admission showed an alert,

active, acyanotic

boy

in moderate respiratory distress with a temperature of 36.5 C, heart and respiratory rates of 120

beats and 38 breaths per minute, respectively, and blood

pressure of 120/80 mm Hg. Peripheral pulses were full and

bounding. Pertinent cardiac findings included a

hyperdy-namic precordium. The apex beat was heaving in nature and

was felt beyond the mid-axillary line in the 5th left

inter-costal space. The area of cardiac dullness was increased but

corresponded with the apex beat. A grade 3/6 systolic murmur and a loud third heart sound were heard over the

apex. The liver edge was 4 cm below the right costal margin.

A nodular mass was palpable over the right middle

abdom-inal quadrant.

Laboratory

Data

Hemoglobin was 10.8 gm/100 ml and hematocrit 31.51%.

The total and differential white blood cell counts, urine

analysis, serum electrolytes, blood urea nitrogen, uric acid,

calcium, phosphorus, total protein, serum albumin to

glob-ulin ratio, serum glutamic oxaloacetic transaminase, glucose, and creatinine were all within normal limits. Catecholamine, serotonin, and 5-HIAA levels in a 24-hour collection of urine

were normal. Antinuclear antibody, febrile agglutinin and

anti-streptolysin 0 titers, C-reactive protein, lupus

erythma-tosus, and latex fixation tests were negative. Urine, throat,

and blood cultures were sterile. Skin tests for histoplasmosis

and tuberculosis were nonreactive. Complement fixation

titers for influenza viruses A, B, and C; parainfluenza viruses

1, 2, and 3; and adenovirus, echovirus, and respiratory

synctial and coxsackie viruses were all less than 1:8. Chest

roentgenograms showed generalized cardiomegaly, normal

pulmonary vasculature, and multiple, discrete, rounded

uncaicified lesions over both lung fields. A 12-lead

electro-cardiogram showed sinus tachycardia, and an intravenous

pyelogram indicated a mass involving the lower pole of the

right kidney. A bone marrow aspirate appeared

hypercel-lular without evidence of malignancy.

Patient Follow-up

A diagnosis of Wilms’ tumor with pulmonary metastases

and high-output congestive heart failure was made. Combi-nation chemotherapy with vincristine and dactinomycin was started and digitalis continued, with little improvement in the hyperdynamic state.

On subsequent examination, a continuous murmur with

systolic accentuation was heard over the right middle

abdominal quadrant. This was well conducted to the back

over the lumbar region. The possibility of intrarenal A-V

fistula due to Wilms’ tumor was considered and further

investigations were done.

CARDIAC CAThETERIZATION DATA

Oxygen

Saturation

Site (%)

Pressures

(mm Hg)

Superior vena cava 75

Right atrium 78 a = 5 (mean = 3)

Right ventricle 80 22/0

Pulmonary artery 82 20/8

Right pulmonary artery 20/8 (wdge 4)

Inferior vena cava 82

Right renal vein 93

Aorta 95 118/78 (mean = 91)

Data Measure

Oxygen consumption 117 ml/min/sq m

Arterial oxygen content 14.9 vol%

Pulmonary artery oxygen content 12.96 vol%

Cardiac output 6.1 liters/mm

Cardiac

index

11.1 liters/mm/sq m

Systemic resistence 640 dyne/sec/cm

FIG. 2. Gross appearance of the right kidney. The upper half

appears normal, whereas the lower half shows tortuous

dilated vessels that branch and are distributed extensively

over the lower renal pole, the associated perirenal fat, and

within the hilum.

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(3)

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Cardiac

Catheterization

Pathological

Findings

Surgery

A-V Fistulas

H H

‘I

1

5 61f 9 1)

FIG. 3. Saggital section of the right kidney showing intrarenal

multilocular cysts with irregular intervening white and grey

tumor masses. Note nodular margins of partial cystic mass

that is well delineated from the adjacent renal tissue (upper

pole).

Serial electrocardiograms showed progressive increases in

Q

RS voltage over precardial leads V,. V, and V6 as well as a

prominent

Q

wave over leads 1, AVF, V3. and V,,. A vector

cardiogram indicated biventricular hypertrophy

character-ized by left and right maximal spatial voltage of 3.46 and 3.3

my, respectively. A phonocardiogram documented a

contin-uous murmur over the renal area. Whole blood and plasma

volumes were 271 and 171 mI/kg, respectively.

During cardiac catheterization (Table I), normal pressures

were recorded over the right side of the heart and the

pulmonary artery. Oxygen saturation was significantly

elevated at the right renal vein. Cardiac output was high and

oxygen consumption was increased. A retrograde aortogram

(Fig. 1) showed a prominent right renal artery, filling of the

inferior vena cava, and neovascularity over the lower pole of

the right kidney characterized by thin, tortuous vessels, A-V

shunting, and delayed tumor circulation. No avascular areas

were seen distal to the A-V fistula.

Because of a persistent hyperdynamic state and

intrac-table congestive heart failure, the patient’s right kidney with

Wilms’ tumor and multiple A-V fistulas was removed. At

nephrectomy, the right renal artery appeared enlarged and

occlusion of the vessel caused the thrill over the tumor to

disappear. A blood sample from the right renal vein had a

plasma renin level of 5.7 ng/Angio. I/mi/hr (supine position, normal diet).

llilfIIlI11tIi1HH

II IIIIII(fHH’lI

±L_

6__7jt

9

FIG. 4. Histologic section from cystic tumor mass in the

lower pole of the right kidney. Open arrow points to internal

elastic lamina of an anomolous blood vessel with a subintimal

proliferative nodule (thin black arrow). Note lack of

continuity of the internal elastic lamina. Thick black arrow

indicates a mass of malignant cells ( x 150).

The right kidney was enlarged and weighed 1 15 gm. The lower half of the renal capsule contained prominent tortuous

vessels that branched extensively (Fig. 2). In the lower pole

of the

saggital

section of kidney was an intrarenal

multilocu-lar cyst containing a tumor mass (Fig. 3). The latter consisted

of masses of cells resembling nephrogenic blastoma with

abundant tubules and pseudoglomeruli, foci of

rhabdomyo-blasts, and dysplastic elements such as cartilage, smooth

muscle, and bizarre myxomatous areas. Mitoses were evident

in all

portions

of the

tumor, which was well-infiltrated in septal locules.

A-V fistulas presented as tortuous, dilated vascular struc-tures involving arcuate arteries and veins in addition to

vessels from the adjacent capsule and perirenal fat.

Micro-scopically the fistulas appeared as thin-walled structures,

abruptly changing to an “arterial” pattern with variably

thickened intima, irregular internal elastica, and foci of

hypertrophic smooth muscle (Fig. 4). Vessel buds consisting

of primitive endothelial cells appeared to merge with

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PRE-OP POST-OP.

COMMENTS

200

:

.- E I6O a I40 0 0 __J I a 20 I00 80 lOmos.

FIG. 5. Preoperative and postoperative clinical profile. Note

the striking improvement in blood volume, heart rate, and

cardiomegaly following removal of the right kidney, which

contained intrarenal A-V fistula and the Wilms’ tumor.

5mos.

EXPERIENCE

AND

REASON

567

nondysplastic renal tissues were characterized by focal

atrophy, fibrosis, and round-cell infiltration. The histologic

findings confirmed the diagnosis of cystic Wilms’ tumor with

multiple A-V fistulas.

Postoperative

Course

After surgery, the patient’s congestive heart failure and

hyperdynamic state disappeared and, during the following

ten months, his heart rate, blood volume, and heart size

gradually returned to normal (Fig. 5).

Although

Wilms’

tumor

accounts

for

approxi-mately 30% of all the malignant solid tumors in

infancy

and

childhood,1#{176}

its

association

with

symptomatic

intrarenal

A-V

fistula

is extremely

rare.11

A continuous

murmur

over

the

renal

area

strongly suggested such an association in the

present

case.

The

diagnosis

was

confirmed

by

angiographic

studies.

The

striking

improvement

following

nephrectomy

firmly

established

intrare-nal

A-V

fistula

as

the

etiologic

factor

in

the

hyperdynamic circulatory state ‘

and

congestive

heart

failure

in our

patient

with

Wilms’

tumor.

The

hemodynamic

alterations

associated

with

A-V

fistula

stem

from

the

fact

that

these

abnormal

A-V

communications

permit

an

increase

in blood

flow

from

the

arterial

circuit

(high

resistance)

to

the

venous

circuit

(low

resistance).’2’4

This

leads

to increases in blood volume, heart rate, cardiac

output,

cardiomegaly,

and,

ultimately,

to a

hyper-dynamic circulatory state and congestive heart

failure,

as in our patient (Fig. 5). In addition,

congenital

or

acquired

forms

of

A-V

fistula

in

a

functioning kidney may produce diastolic

hyper-tension.’48

That

this

change

may

also

occur

in

patients

with

intrarenal

A-V

fistula

due

to Wilms’

tumor

has

been

recently

reported

by

Sukarochana

et al.9 The

mechanism

of diastolic

hypertension

in

these

patients

has

been

attributed

to

relative

ischemia

due

to a decrease

in blood

flow

distal

to

the

A-V

fistula.’418

The

pathogenesis

of

intrarenal

A-V

fistula

formation in association with Wilms’ tumor has

been

attributed

to various

factors,

such

as erosion

of

the

vessels

by

tumor

invasion2

or

failure

of

intrarenal

vessels

to

differentiate

into

arteries,

capillaries,

and

veins.12

In

our

patient

histologic

studies

of

the

affected

kidney

showed

a

wide

spectrum

of

tissue

dysplasia

characteristic

of

Wilms’

tumor.

The

relatively

early

age

of

occurrence

of A-V

malformations

suggests

that

in

this case abnormal arteriovenous communication

could

be

congenital

in

origin,

similar

to

Wilms’

tumor,2”2”9’2#{176}

and

that

both

could

be

an

expres-sion

of

a

common

induction

mechanism.2’

Recently,

Folkman

et

al.22’2’

isolated

a

tumor

angiogenesis

factor

(TAF)

from

human

as well

as

animal

tumors

and

suggested

its

role

in

the

formation of new capillaries. Whether an

exces-sive

production

of TAF

with

consequent

forma-tion

of numerous

blood

vessels

that

fail

to

differ-entiate

into

arteries,

veins,

and

capillaries

could

lead

to A-V

malformations

in a child

with

Wilms’

tumor

remains

a matter

of speculation.

Although

the

presence

of a systolic

bruit

over

the

renal

area

strongly

suggests

intrarenal

A-V

fistula,

aortography

provides

the

best

means

of

confirming

the

diagnosis

and

for

defining,

preoperatively,

the

main

arterial

and

venous

structures

entering

into

the

malformation.

The

striking improvement in the cardiovascular status

of

our

patient

following

nephrectomy

suggests

the

importance

of surgery

in some

children

with

Wilms’

tumor

associated

with

a

symptomatic

intrarenal

A-V

fistula.

SHYAMAL

K.

SANYAL,

F.A.A.P.,

F.A.C.C.

VIcroR SALDIVAR,

M.D.

THOMAS

P.

COBURN,

M.D.

E.

L.

WRENN, JR.

MAHESH KUMAR,

M.D.

Pediatric

Cardiology,

Surgery,

and

Pathology Services,

St. Jude

Children’s

Research

Hospital

Memphis,

Tennessee

ADDRESS FOR REPRINTS: (S.K.S.) Pediatric Cardiologist,

St. Jude Children’s Research Hospital, P.O. Box 318,

Memphis, Tennessee 38101.

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REFERENCES

1. Miller RW, Fraumeni JF, Manning MD: Association of Wilms’ tumor with aniridia, hemihypertrophy and

other congenital malformations. N EngI

J

Med

270:922, 1964.

2. Comes MMR, Bernatz PE: Arteriovenous fistulas: A

review of ten years’ experience at the Mayo Clinic.

Mayo Clin Proc 45:81, 1970.

3. Hidai M, Fukoka H, Murayama

J:

Arteriography in

Wilms’ tumor.

J

Urol 1 10:347, 1973.

4. Farah

J,

Lofstrom JE: Angiography of Wilms’ tumor.

Radiology 90:775, 1968.

5. Nebesar BA, Fleischli DJ, Pollard

JJ,

Griscom MT:

Arteriography in infants and children with

empha-sis on Seldinger techniques and abdominal diseases.

Am

J

Roentgenol Radium Ther Nucl Med 106:81,

1969.

6. Moes CAF, Burrington JD: The use of aortography in

the diagnosis of abdominal masses in children.

Radiology 98:59, 1971.

7. Cremin BJ, Kaschula ROC: Arteriography in Wilms’

tumor: The results of 13 cases and comparison to

renal dysplasia. Br

J

Radiol 45:415, 1972.

8. Meng CH, Elkin M: Angiographic manifestations of

Wilms’ tumor: An observation of six cases. Am

J

Roentgenol Radium Ther NucI Med 106:81, 1969.

9. Sukarochana K, Tolentino W, Kiesewetter WB: Wilms’

tumor and hypertension.

J

Pediatr Surg 7:573, 1972.

10. Fleming ID, Johnson W: Clinical and pathological

staging as a guide in the management of Wilms’

tumor. Cancer 26:660, 1970.

11. Klapproth HJ: Wilms’ tumor: A report of 45 cases and

an analysis of 1,351 cases reported in world

litera-hire from 1940 to 1958.

J

Urol 81:633, 1959.

12. Kittredge RD. Kanick V. Finby N: Arteriovenous

fistu-las. Am

J

Roentgenol Radium Ther NucI Med

106:81, 1969.

13. Hipona FA, Sanyal 5K, Browne MJ: Congenital left

coronary artery fistula draining into right atrium:

An uncommon cause of continuous murmur in

childhood: Arch Dis Child 46:101, 1971.

14. Maldonado JE, Sheps 5G. Bernatz PE, et a!: Renal

arterio-venous fistula: A reversible cause of

hyper-tension and heart failure. Am

J

Med 37:499, 1964.

15. Boijesen E, Kohler R: Renal arteriovenous fistula. Acta

Radiol 57:433, 1962.

16. Grace JT, Staubitz W, Lessmahn F, Egan R: Intrarenal

arteriovenous fistula. Arch Surg 81:1 18, 1960.

17. Crummy AB Jr. Atkinson RJ, Caruthers SB Jr:

Congenital renal arteriovenous fistulas.

J

Urol

93:24, 1965.

18. DeBeukelaer M, Schreiber MH, Dodge MF, Travis LB:

Intrarenal arteriovenous fistulas following needle

biopsy of the kidney.

J

Pediatr 78:266, 1971.

19. Fowler M: Differentiated nephroblastoma: Solid, cystic

or mixed.

J

Pathol 105:215, 1971.

20. Uson AC, Del Rosario C, Melicow MM: Wilms’ tumor

in association with cystic renal disease: Report of

two cases.

J

Urol 83:262, 1960.

21. Willis BA: The Borderland of Embryology and

Pathol-ogy. London, Butterworth & Co, 1958, p 197.

22. Folkman

J,

Merler E, Abernathy C, Williams G:

Isola-tion of a tumor factor responsible for angiogenesis.

J

Exp Med 133:275, 1971.

23. Folkman

J:

Tumor angiogenesis: Therapeutic

implica-tions. N EngI

J

Med 285:1182, 1971.

ACKNOWLEDGMENT

The authors wish to thank Mr. John Gilbert and Drs.

Warren Johnson, Walter T. Hughes, Ralph C. Tierney,

Courtney Anthony, and Alvin Mauer for critical review of

the manuscript.

Persistent

Mullerian

Structures

in a Male

Neonate

A

2-week-old

male

infant

was

diagnosed

as

having

persistent

Mullerian

structures.

Micro-scopically

normal

testes

were

found,

as well

as a

uterus,

cervix,

and

fallopian

tubes.

Plasma

testos-terone

values

responded

normally

to

human

chorionic

gonadotrophin

stimulation.

This

condi-tion

at times

is familial,

and

genetic

counseling

is

indicated.

CASE

REPORT

A 2-week-old white boy presented with a history of a niass

in the left groin. This mass was not present at birth. There is

no family history of inguinal mass and the patient has no

siblings. Physical examination revealed a normal male infant

with a 2-cm to 3-cm hard mass in the left inguinal area. This

mass was reducible with pressure but immediately

reap-peared. It did not descend into the scrotum. The scrotum

appeared normal, and a left testis was palpated in the

scrotum. The right testis could not be palpated in the canal

or scrotum. The penis was circumcised and appeared

normal.

He was admitted for repair of his inguinal hernia. At

surgery, a hard mass was found protruding through the

internal ring. No hernia sac was present. When the mass was

freed from the circumference of the internal ring, it was the

consistency and shape of an infant uterus. This was delivered

through the incision and in so doing, the testicle in the left

scrotum and the testicle within the abdomen were also

delivered. Well-developed fallopian tubes were found within

the broad ligament structure.

The vas deferens were found on each side extending down

within the substance of the broad ligament into the cervix.

The vas could not be dissected from the substance of this

cervical tissue without danger of destroying the vas.

Conse-quently, the uterus was excised supracervically. Both testes

were placed into the scrotum and sutured to the thighs.

The biopsies of the two gonads were consistent with

neonatal testes, in which seminiferous tubules were

identi-fled. The pathologist identified early stages of endometrium

formation in the uterus, and the endometrial channel

appeared to be bifid.

Postoperatively, a buccal smear for sex chromatin revealed

no

Barr bodies, and the karotype revealed a normal 46 XY

male pattern. A 24-hour urine specimen showed the

17-ketosteroids to be 1.0 Ing/24 hr. The 17-OH corticosteroid

determination was not performed as an interfering substance

was present that contaminated the specimen. Treatment

with 1,500 units of human chorionic gonadotrophin

(6)

1976;57;564

Pediatrics

Shyamal K. Sanyal, Victor Saldivar, Thomas P. Coburn, E. L. Wrenn and Mahesh Kumar