Intracaval and Atrial Involvement with Nephroblastoma: Review of National Wilms Tumor Study-3

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INTRACAVAL AND ATRIAL INVOLVEMENT WITH NEPHROBLASTOMA: REVIEW OF NATIONAL WILMS TUMOR STUDY-3 MICHAEL L. RITCHEY,* PANAYOTIS P. KELALIS,t NORMAN BRESLOW, KENNETH P. OFFORD, STEPHEN J. SHOCHAT AND GIULIO J. D'ANGIO From the Department of Urology and the Section of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota; National Wilms' Tumor Study, Seattle, Washington; Stanford University Medical Center, Stanford, California, and Children's Cancer Research Center, Philadelphia, Pennsylvania

ABSTRACT

We reviewed the records of 77 children enrolled in the National Wilms Tumor Study-3 who had involvement of the inferior vena cava with tumor thrombus. None of these patients received preoperative chemotherapy or radiotherapy. Ultrasonography and inferior venacavography were more helpful than computerized tomography in the preoperative diagnosis. The median followup for the group was 2.7 years. The 3-year survival rates for patients with intracaval involvement were determined by stage (88, 89 and 62 per cent for stages II, III and IV, respectively). The most important prognostic factor was histological type. The level of vena caval involvement had no effect on survival; all 16 patients with atrial involvement survived 3 or more years. We continue to recommend appropriate surgical excision of the tumor and thrombus when it is technically feasible. (J. Ural., part 2, 140: 1113-1118, 1988) Involvement of the inferior vena cava with tumor thrombus has been reported in 5 to 10 per cent of the patients with Wilms tumor. 1 As the treatment of nephroblastoma has evolved it has become apparent that patients with extensive local disease or metastatic lesions can be cured by the combination of chemotherapy, radiotherapy and surgery. 2 Management of nephroblastoma with vascular extension can be a difficult surgical task but vascular invasion was reported to have no significant effect on survival in the early National Wilms Tumor Study (NWTS) trials. 3 Breslow and associates reported that the risk of relapse was increased in NWTS-2 patients with an intravascular tumor thrombus. 4 Therefore, we reviewed the records of patients with vena caval involvement enrolled in NWTS-3, the latest national study. 1 At the same time we updated and extended observations made earlier by Nakayama and associates on the intracardiac extension of this tumor. 5 The clinical presentation, imaging techniques for diagnosis and operations performed were evaluated. Survival and complications in the treatment of these difficult cases also were assessed.

associated congenital anomalies, diagnostic evaluation, treatment received, complications encountered and survival status. The operation and pathology reports were reviewed by us and used to assign a stage to the disease on the basis of the system proposed by NWTS: stage II-17 patients, stage III-37 patients and stage IV-23 patients. 7 All patients had at least stage II disease by reason of extension into the inferior vena cava. None of the patients reviewed received preoperative chemotherapy or radiation therapy. Patient age ranged from 8 months to 14 years, with a median age of 4 years. At diagnosis 7, 29 and 41 patients were less than 2, 2 to 4 and greater than 4 years old, respectively. There were 39 girls and 38 boys. Of the patients 58 were white, 17 black and 5 Hispanic. Of the tumors 46 arose from the right kidney and 31 from the left kidney. The most common presenting sign was an abdominal mass in 32 patients (42 per cent), followed by gross hematuria in 23 (30 per cent). On evaluation, however, a mass was palpable in 94 per cent of the patients. Only 5 patients presented with signs or symptoms suggestive of intravascular involvement: 2 MATERIALS AND METHODS with a varicocele, 2 with hepatomegaly secondary to hepatic There were 2,496 patients registered in NWTS-3 from May vein obstruction and 1 with a large atrial thrombus who was in 2, 1979 to April 8, 1987. Of these patients 631 were excluded congestive heart failure (table Nine patients (11. 7 per cent) had associated congenital from this review because of inoperable disease, bilateral involvement, previous therapy, misdiagnosis and refusal of treat- anomalies, including 3 with hemihypertrophy and 3 with skelment. The incidence of vena caval involvement in the excluded etal abnormalities. A total of 18 patients had a positive family patients was known only for the children with bilateral involve- history for cancer but none of the occurrences was Wilms ment. Of these 152 children 10 had vena caval thrombus. 6 The tumor. The level of vena caval thrombus was infrahepatic in 4 7 charts of 77 patients with Wilms tumor and intracaval tumor patients (61 per cent), retrohepatic in 14 (18 per cent) and involvement registered in NWTS-3 were reviewed. The incidence of vena caval or atrial thrombus was 4.1 per cent (77 of atrial in 16 (21 per cent). Of the 16 patients with atrial involvement 9 were included in the earlier NWTS report by Nakayama 1,865 evaluable patients). 5 The clinical records of the patients were reviewed for patient and associates. These patients now have a longer followup and are included in this review so that all patients with intracaval age at diagnosis, sex, race, presenting signs and symptoms, extension who are enrolled in NWTS-3 are evaluated. The diagnosis of intracaval thrombus was made correctly in 48 of Supported by United States Public Health Service Grant CA-42326 and the National Cancer Institute. the 77 patients (62 per cent) before the initial operation. Vena * Current address: Department of Urology, Wilford Hall, United caval extension was detected at operation in 28 patients and States Air Force Medical Center, Lackland Air Force Base, Texas postoperatively in 1. The imaging techniques performed pre78236. t Requests for reprints: Department of Urology, Mayo Clinic, 200 operatively are listed in table 2. First St., S. W., Rochester, Minnesota 55905. The most common finding on excretory urography (IVP) was 1113

n

1114

RITCHEY AND ASSOCIATES

TABLE 1.

TABLE 2.

Clinical presentation of 77 patients with Wilms tumor and intracaval thrombus Sign or Symptom

No. Pts.

(%)

Abdominal mass Gross hematuria Pain Varicocele Hepatomegaly Congestive failure Other

32 23 14 2 2 1 3

(42) (30) (18) (2.6) (2.6) (1.3) (3.9)

Radiographic evaluation of Wilms tumor in vena caval thrombus Study

IVP Ultrasonography CT Venacavography Angiography MRI

No. Pts. Examined*

77 patients

with

Correct Diagnosis of Vena Cava! Thrombus No. Pts. (%)

50 56 38 23 9 2

33 16 20 5

2

59 42

87 56 100

the 4 patients in whom the thrombus remained 3 had adherence of the thrombus to the wall of the inferior vena cava and it could not be extracted. The remaining patient had extensive metastatic disease and no attempt was made to remove the intracaval extension. Of 12 patients noted by the surgeon to have invasion of the inferior vena cava 6 underwent partial vena caval resection. The pathologist confirmed invasion in 5 of these patients. In the other 6 patients invasion of the inferior vena cava could not be confirmed because no vena caval wall was removed. One of these patients had invasion of the renal vein wall. Of these 6 patients 3 had gross residual disease within the inferior vena cava and 3 had presumed microscopic residual disease. Of the patients with a portion of the vena cava excised only 1 had gross and 1 had microscopic residual disease. Preoperative rupture occurred in 7 patients. Operative spillage occurred locally in 47 patients and diffusely in 11. The rate of local spillage was high because cutting across the tumorcontaining renal vein was considered a local spill. The opposite kidney was not explored in 6 patients and only palpated in 10. In 31 patients the exploration was performed after the nephrectomy was completed.

* Patient may have undergone more than 1 study. PATHOLOGICAL FINDINGS

a renal mass with distortion of the collecting system. A nonfunctioning kidney was present in 14 patients (28 per cent). The vena caval thrombus was detected in 33 of the 56 patients (59 per cent) who underwent ultrasonography. Sonography correctly diagnosed the thrombus in 14 of the 15 patients with atrial extension in whom the procedure was used. Ultrasound examination was done postoperatively in only 3 of the 15 patients, the diagnosis of vena caval thrombus having been missed preoperatively. Computerized tomography (CT) scanning, used in 38 patients, revealed intracaval extension in 16. Magnetic resonance imaging (MRI) was performed in 2 patients and was diagnostic in both cases. Renal arteriography was done in 9 patients and confirmed vena caval extension in 5. In only 1 of these 5 patients did a noninvasive study not also confirm this diagnosis. Thrombus in the vena cava was identified in 20 of 23 patients (87 per cent) who underwent inferior venacavography. In 3 cases the venacavographic finding was interpreted as external compression of the inferior vena cava by the renal mass. SURGERY

All patients underwent primary nephrectomy. An abdominal incision was used in 54 patients (70 per cent) and a thoracoabdominal incision was used in 13 (17 per cent). A midline incision was combined with median sternotomy in 10 patients with atrial involvement. For removal of the vena caval thrombus the most frequent method was venacavotomy with proximal and distal vascular control. Extraction was manual in 36 patients and by a Fogarty or Foley balloon in another 11. In 10 patients the thrombus was removed by venacavotomy without vascular control. Partial resection of the inferior vena cava was performed in 6 patients but none had complete interruption of the inferior vena cava. Eight patients with an atrial thrombus required cardiopulmonary bypass. En bloc removal (kidney and thrombus) was possible in 31 patients and separate removal was done in another 40. A total of 25 patients had residual tumor after thrombus removal: 11 had microscopic residual and 14 had gross residual disease within the vena cava. The vena caval thrombus was left in place in 6 patients, 5 of whom did not have vena caval involvement detected preoperatively. The thrombus was removed from 2 of them subsequently. In 1 patient the thrombus was detected intraoperatively but the surgeon chose not to remove it. In the other patient hypotension in the postoperative period led to the evaluation after the thrombus was missed at operation. Of

Histological type was favorable in 67 patients and unfavorable in 10. Of the latter 10 patients 5 had anaplastic sarcoma (4 rhabdoid and 1 clear cell type), 4 had diffuse anaplasia and 1 had focal anaplasia. All tumors were large and 52 of 77 (68 per cent) were larger than 10 cm. in diameter. Invasion of the capsule was noted in 10 cases and penetration of the capsule occurred in 38 kidneys. A total of 13 patients had residual tumor beyond the surgical margin. There was local extension into adjacent organs or structures (other than the inferior vena cava) in only 7 children. Of 77 patients 22 (29 per cent) had lymph node involvement (table 3). There were 11 patients with only hilar, 8 with only para-aortic, and 3 with hilar and para-aortic nodal involvement. RADIATION AND CHEMOTHERAPY

A total of 69 patients (90 per cent) received radiation. Thirteen patients were given 1,000 cGy and 31 received 2,000 cGy to the abdomen. The whole abdomen was treated in 11 patients because of diffuse spillage. A total of 25 patients received pulmonary radiation in addition to treat metastatic deposits in the lung (22 children) or to include the operative field in cases of atrial involvement (3). All patients underwent chemotherapy: 11 received a 2-drug regimen (actinomycin D and vincristine) and 59 received a 3drug regimen (actinomycin D, vincristine and doxorubicin). In 7 patients 4 drugs were used, cyclophosphamide being added to the aforementioned 3 drugs. COMPLICATIONS

Complications occurred in 33 patients (43 per cent) (table 4). The most frequent complication was major intraoperative hemorrhage, which was defined as an operative blood loss exceeding 50 ml./kg. body weight. Of the 25 patients 10 had intraoperative blood losses of greater than 100 ml./kg. There were no operative deaths but cardiac arrest due to severe hypotension occurred in 3 patients. The incidence of complications did not correlate with an accurate preoperative diagnosis of the vena caval extension, the method of thrombus removal or the level of vena caval involvement. However, in the 4 patients with atrial extension not diagnosed preoperatively the thrombus was not removed at the initial operation. Survival was not significantly altered in patients who had complications. A high complication rate also was noted in the review by Nakayama and associates. 5 One complication seen postoperatively was occlusion of the inferior vena cava after removal of the thrombus (5 patients).

1115

INTRACA-VAL I:NVOLVE}11Ef'JT r1~,,y \VILlvfS TUMOR TABLE

3. Lymph node status of 77 patients with Wilms tumor and uena caual thrombus

Lymph Nodes

No. Pts.

No. Deaths

% 3-Yr. Survival*

Neg. Pos.: Hilar only, 11 Aortic only, 8 Hilar and aortic, 3

55 22

9 4

80 79

F'f"C=i---L (23) (7) (10)

80

~

(5)

60

(7)

ca>

·2:

* Two-tailed log rank p value, 0. 79. TABLE

100

:i (./)

40

3-yr survival, % Stage 2 (n = 17) Stage 3 (n = 37) Stage 4 (n = 23)

4. Complications in 33 patients with Wilms tumor after

surgical removal of intracaual thrombus

20

No. Pts.* Extensive hemorrhage Bowel obstruction Obstructed inferior vena cava Nonlethal intraoperative cardiac arrest Other

25 7 5 3 2

* Patient may have had more than l complication.

Evaluation of 2 of these patients for ascites 2 months postoperatively led to the discovery of the vena caval occlusion. One patient had swelling of the left lower extremity 1 month postoperatively and total obstruction of the inferior vena cava was found. In 1 patient portal hypertension developed secondary to vena caval thrombosis and a splenorenal venous shunt was required. The remaining patient did not have any symptoms related to vena caval occlusion and the diagnosis was made by routine postoperative imaging studies. The cause of vena caval obstruction after removal of a tumor thrombus could be recurrent tumor, scarring or bland thrombus secondary to injury of the endothelium. Of these 5 patients 4 are alive without evidence of disease at 21 to 63 months postoperatively. One patient died of the Budd-Chiari syndrome. No autopsy was performed and it is unclear whether the inferior vena cava was obstructed by residual tumor. In all 5 of these patients the thrombus was excised at the initial operation and only the patient who died had gross residual tumor within the inferior vena cava. Without standardization of the postoperative imaging evaluation the true incidence of the occurrence of this complication will remain unknown.

0 0

2

3

4

5

Years after diagnosis Survival curves by stage in patients with Wilms tumor who had vena caval and atrial thrombi. Numbers of patients in each category are shown in parentheses. Numbers of patients observed for 2 and 4 years, respectively, are 10 and 5 stage 2, 23 and 7 stage 3, and 15 and 7 stage 4. Two-tailed log rank p value <0.0333. FIG. 1.

100

(19) 80 ~

"

60

<1i >

·2:

:l (I)

(4) 40

(2) 20

3-yr survival, % 86

-

Favorable (n=67)

-

Unfavorable (n = 10)

35

0 0

SURVIVAL

Survival was the primary end point. Kaplan -Meier survival curves were used to estimate survival and log rank tests were performed to compare survival among groups. 8 • 9 All p values were considered to be 2-sided, with the conventional 0.05 level taken to reflect evidence of significance. At last followup 64 patients were alive without evidence of disease and 13 patients had died, 11 of tumor progression and 2 of treatment complications. The median followup for the entire group was 2.7 years. Actuarial survival by final stage is depicted in figure 1. The 3-year rate was 87.5 per cent for stage II, 88.5 per cent for stage III and 62.3 per cent for stage IV disease (p = 0.0333). The level of vena caval involvement (infrahepatic, retrohepatic or atrial) alone was not predictive of survival. All 16 patients (100 per cent) with atrial extension survived (p = 0.0495) and all had favorable histological types. The most important indicator was histological pattern (fig. 2). The 3-year survival rate for the 67 patients with a favorable histological type was 86 per cent and for the 10 with an unfavorable histological type it was 35 per cent (p = 0.0002). Interestingly, lymph node status did not have a statistically significant impact on survival in this series (table 3). However, when the level of lymph node involvement was considered the 11 patients with positive para-aortic nodes had a 3-year survival rate of 70 per cent, compared to 91 per cent for the 11 patients with hilar nodes. Although this trend toward decreased survival was not significant it may just reflect the small number of patients and deaths in each category.

88 89 62

2

3

4

5

Years after diagnosis Survival curves for patients with favorable and unfavorable histological types. Numbers of patients in each category are shown in p_arentheses. Numbers of patients observed for 2 and 4 years, respectively, are 45 and 19 favorable, and 3 and O unfavorable histological type. Two-tailed log rank p value <0.0002. FIG. 2.

Other variables evaluated were age, sex, race, tumor spillage, residual disease, preoperative rupture, radiation dose and type of chemotherapy. None of these was predictive of survival. It has been suggested that patients with intracaval tumor extension should receive pulmonary irradiation. 10 This recommendation is based on the assumption that all of these patients probably have micrometastases. Excluding patients with stage IV disease, only 3 children with a favorable histological type received pulmonary radiation and 3 with atrial involvement were given radiation to the lower mediastinum. There were no deaths or pulmonary relapses in these 6 patients. A total of 41 patients with stage II or III favorable histological type did not receive pulmonary radiation. In this group only 1 patient had a pulmonary relapse and 2 died. These data suggest that pulmonary irradiation should be reserved for only those patients with radiologically detectable pulmonary metastases. DISCUSSION

Surgical management of nephroblastoma extending into the inferior vena cava is a daunting surgical challenge. Previous reports have stressed the magnitude of the operation for re-

1116

RITCHEY AND ASSOCIATES

moval of the thrombus, particularly when there is extension to the atrium. 5 •11 However, this difficulty is increased considerably when the diagnosis is missed preoperatively. 11 The clinical findings of intravascular extension of Wilms tumor can vary by level of obstruction. 10 If the mid vena cava is obstructed varicocele, albuminuria and hematuria may result. Obstruction of the inferior vena cava above the hepatic veins can result in hepatomegaly, ascites and hepatic dysfunction. A child with atrial extension of the thrombus may present with congestive heart failure or have a cardiac murmur on examination. In this series outward clinical signs of inferior vena cava thrombus frequently were lacking. Imaging studies are the key to a correct diagnosis. Nonfunction of a kidney during an IVP suggests renal vein or inferior vena cava thrombus but it could result from obstruction of the collecting system or near total replacement of the renal tissue by tumor. 12 In the past inferior venacavography was used to confirm or exclude intravascular tumor. Interpretation of the results often is difficult. Extrinsic compression of the vena cava by the renal mass may simulate intracaval extension. Furthermore, with crying or straining during the examination all blood can be forced into the collaterals, where it mimics vena caval obstruction by thrombus. 13 In recent years noninvasive imaging has had an important role in the detection of tumor in the inferior vena cava. Realtime ultrasonography seems to be the preferred modality. 14 In most cases it can differentiate between extrinsic compression and intracaval thrombus. It can determine the extent of thrombus throughout the length of the vena cava, whether it is attached to the intima and, if so, where it is attached. An echocardiogram can be used to evaluate lesions that extend above the diaphragm. Other noninvasive techniques are CT and MRI. CT may provide other staging information, such as lymph node involvement, extension of the primary tumor to other organs or bilateral involvement but it appears to be less useful in detecting inferior vena cava disease. Because the attenuation values for the tumor thrombus are similar to those for blood false-negative results are possible. In addition, a pseudothrombus may appear because of high blood flow from the renal vein on the affected side. 15 MRI is a promising new modality but experience is limited; it was used in only 2 of our patients for example. Despite the wide range of imaging techniques available the intravascular extension of tumor was not diagnosed preoperatively in 29 patients (table 5). Most of the missed lesions were small tumor thrombi in the infrahepatic vena cava at the level of the kidney. These smaller lesions do not present as difficult a problem when discovered intraoperatively. A frequent reason for failure to diagnose the thrombus was not performing the proper diagnostic test. In a third of these patients either no preoperative imaging studies were done or only an IVP was performed. The most accurate x-ray study in these patients was inferior venacavography. This finding contradicts that in recent reports that favor ultrasonography as the initial imaging study in the preoperative evaluation of patients with Wilms tumor. 14 ·16 There could be several explanations for this finding: 1) this is a retrospective review, and only a summary by the clinician and not the radiological interpretation of the ultrasound find-

Radiographic evaluation in 29 patients with Wilms tumor in whom vena caval thrombus was missed preoperatively

TABLE 5.

Preop. Imaging Studies Level of Thrombus

Total No. Pts.

Atrial Retro hepatic Infrahepatic

5 20

4

Ultrasonography 1 2 13

CT

Venacavography

Angiography 1

12

1

2

ings is sent to the NWTS statistical center, 2) the percentage of patients in whom real-time sonography was performed is unknown and 3) this was a multicenter study, with a large number of participating institutions and with many different radiologists performing the examinations. Also, this is a select group. Inferior venacavography was done for suspected tumor rather than for routine examination. Ultrasound is more often a screening test, that is it is done in more patients and hence has a smaller yield. We continue to recommend real-time ultrasonography for the initial evaluation of the inferior vena cava because it is noninvasive and easily performed. If this study is inconclusive inferior venacavography then should be performed. There are reports that chemotherapy and radiation therapy can be successful in shrinking the intravascular tumor preoperatively.17-19 Proponents of this approach believe that it simplifies later removal of the renal mass. However, 1 report documents increased difficulty in removing the thrombus because of dense adherence to the vein wall after preoperative chemotherapy. 2° Certainly, risk and morbidity are associated with removal of vena caval &nd atrial thrombi. That the intracaval thrombus is responsive to chemotherapy or radiation therapy also was observed in this series: 3 of the 4 patients in whom the vena caval thrombus was not excised were without disease 33, 36 and 43 months postoperatively. Two of these patients had resolution of the thrombus on serial ultrasound examination. One patient had persistent vena caval obstruction on followup venacavography but had no evidence of disease 20 months after chemotherapy was completed. The remaining patient in whom the thrombus was left died of progressive disease. No autopsy was performed and the status of the inferior vena cava at death is unclear. Two of these 4 patients had stage IV and 2 had stage III disease. Only 1 of the patients had upgrading to a higher stage because of the residual thrombus. None of the children received additional treatment beyond NWTS guidelines for the assigned stage. Patients who have undergone preoperative chemotherapy are excluded from randomization in NWTS. Therefore, any patients with intracaval extension who received preoperative chemotherapy were excluded from this review. Although morbidity with primary surgical excision was high, the prognosis in these patients compares favorably with NWTS-3 results. 21 A log rank comparison of survival revealed no significant difference when patients were matched by stage and histological type. We continue to recommend appropriate surgical excision of the tumor and thrombus when it is feasible technically, followed by chemotherapy and possibly radiation according to NWTS guidelines. However, when the tumor is massive or densely adherent and invading the inferior vena cava preoperative chemotherapy to shrink the tumor and thrombus is appropriate. This then can be followed by nephrectomy and removal of the residual thrombus, if any. The use of this approach in carefully selected patients may decrease the morbidity in the surgical treatment of these difficult cases. It also may decrease the high incidence (32 per cent) of residual disease within the vena cava noted in these patients. Although survival was not significantly altered, the potential for the lethal complication of tumor embolization certainly exists if the renal vein is transected and gross tumor is left within the vena cava. 22 If the level of the vena caval thrombus can be determined accurately preoperatively a careful, planned surgical approach can be made. For infrahepatic lesions an abdominal approach is sufficient. The vena caval thrombus can be removed by venacavotomy after proximal and distal vascular control is obtained. 11 When the thrombus adheres to the vena caval wall the thrombus often can be delivered with the passage of a Fogarty or Foley balloon catheter. Patients with atrial extension may require cardiopulmonary bypass for thrombus removal. In these patients a midline

1117

INTRA CA VAL INVOLVEMENT IN WILMS TUMOR

abdominal incision with median sternotomy often is used. The surgical technique has been well described. 5 • 16 For extremely large upper pole tumors or involvement of the retrohepatic vena cava a thoracoabdominal incision affords excellent exposure. Mobilization of the liver superiorly and medially by rotation through the divided diaphragm exposes the intrahepatic vena cava. The vena cava can be occluded superiorly at the atrial level. Use of the Pringle maneuver may decrease blood loss during thrombus removal and prevent sequestration of blood in the liver.' Large renal masses may make it necessary to remove the kidney to provide better exposure of the vena cava for thrombectomy. The tumor and thrombus were removed separately in 40 patients with no difference in the survival from that of those having en bloc removal. When this maneuver is performed vascular control of the vena cava is essential to avoid embolization. No instances of pulmonary embolization of tumor occurred but this complication was reported with division of the renal vein when thrombus was left within the inferior vena cava. 22 Vena caval resection may be indicated when there is invasion of the vena caval wall rather than a free-floating thrombus alone. In this series only partial resection of the vena caval wall at the junction of the renal vein was required. It often has been stated that segmental resection of the infrahepatic vena cava can be accomplished safely for right renal lesions because the left renal vein usually has adequate collateral blood flow from the adrenal, lumbar and gonadal veins. This statement may not always be true in younger children. 23 If there are many significant venous collaterals due to thrombotic obstruction of the vena cava the procedure may be well tolerated. Measurement of renal vein pressures after temporary occlusion of the renal vein has been used as an objective method to determine adequate collateral flow. 24 Pressures less than 35 cm. water indicate a favorable outcome. If pressures in the renal vein are increased the renal vein must be drained into a lower pressure system. An important fact to remember during exploration in these patients is that the thrombus can extend into other tributaries of the vena cava. In this series 5 patients had caudal extension of the intracaval thrombus. The tumor also was noted to extend into the gonadal vein, contralateral renal vein, adrenal vein and hepatic vein. Also, certain operative findings may suggest intravascular extension when it has not been diagnosed correctly preoperatively. Excessive bleeding from dilated superficial and retroperitoneal collaterals is a clue to obstruction of the vena cava. More ominous is the finding of sudden unexplained hypotension, which can result from embolization of the tumor thrombus. CONCLUSION

The surgical management of patients with Wilms tumor and intracaval extension remains a formidable challenge and excision of the lesion is associated with considerable morbidity. However, survival of these patients is comparable to that of patients with similar surgical stage and histological type without vena caval extension. The level of vena caval involvement alone was not of prognostic significance; all 16 patients with atrial extension are alive without evidence of disease. The most significant determinants of survival were histological type and stage. Since most patients with intravascular extension of tumor thrombus have no clinical manifestations, vena caval thrombus should be excluded preoperatively in all patients with Wilms tumor. Careful preoperative evaluation is essential to plan the proper operative approach. We continue to recommend appropriate surgical excision of the tumor and thrombus when it is technically feasible. However, when the tumor is massive or invasion of the inferior vena cava in all likelihood precludes its removal, biopsy of the tumor followed by chemotherapy to

shrink the tumor and thrombus may be an attractive alternative. The use of this approach in selected patients may decrease the morbidity encountered in the surgical treatment of these difficult cases but further data must be collected in order to determine that this is indeed true. Many pathologists, surgeons, pediatricians, radiation therapists and other health professionals managed these children. Also, the staff of the Data and Statistical Center of the National Wilms Tumor Study, and Ms. Cindy Benson provided assistance and cooperation. REFERENCES 1. Clayman, R. V., Sheldon, C. A. and Gonzales, R.: Wilms' tumor: an approach to vena caval intrusion. Prog. Ped. Surg., 15: 285, 1982.

2. D'Angio, G. J., Evans, A., Breslow, N., Beckwith, B., Bishop, H., Farewell, V., Goodwin, W., Leape, L., Palmer, N., Sinks, L., Sutow, W., Tefft, M. and Wolff, J.: The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study. Cancer, 47: 2302, 1981. 3. Leape, L. L., Breslow, N. E. and Bishop, H. C.: The surgical treatment of Wilms' tumor: results of the National Wilms' Tumor Study. Ann. Surg., 187: 351, 1978. 4. Breslow, N., Churchill, G., Beckwith, J. B., Fernbach, D. J., Otherson, H. B., Tefft, M. and D'Angio, G. J.: Prognosis for Wilms' tumor patients with nonmetastatic disease at diagnosisresults of the Second National Wilms' Tumor Study. J. Clin. Oncol., 3: 521, 1985. 5. Nakayama, D. K., Norkool, P., deLorimier, A. A., O'Neill, J. A., Jr. and D'Angio, G. J.: Intracardiac extension ofWilms' tumor: a report of the National Wilms' Tumor Study. Ann. Surg., 204: 693, 1986. 6. Blute, M. L., Kelalis, P. P., Offord, K. P., Breslow, N., Beckwith, J.B. and D'Angio, G. J.: Bilateral Wilms' tumor. J. Urol., 138: 968, 1987. 7. Farewell, V. T., D'Angio, G. J., Breslow, N. E. and Norkool, P.: Retrospective validation of a new staging system for Wilms' tumor. Cancer Clin. Trials, 4: 167, 1981. 8. Kaplan, E. L. and Meier, P.: Nonparametric estimation from incomplete observations. J. Amer. Stat. Ass., 53: 457, 1958. 9. Mantel, N.: Ranking procedures for arbitrarily restricted observation. Biometrics, 23: 65, 1967. 10. Grosfeld, J. L. and Weber, T. R.: Surgical considerations in the treatment of Wilms' tumor. In: Wilms' Tumor (Nephroblastoma) and Related Renal Neoplasms of Childhood. Edited by F. Gonzalez-Crussi. Boca Raton, Florida: CRC Press, chapt. 14, pp. 263-283, 1984. 11. Kramer, S. A.: Complications of Wilms' tumor and nephroblastoma. In: Urologic Complications: Medical and Surgical, Adult and Pediatric. Edited by F. F. Marshall. Chicago: Year Book Medical Publishers, chapt. 25, pp. 317-330, 1986. 12. Kramer, S. A. and Kelalis, P. P.: Pediatric urologic oncology. In: Adult and Pediatric Urology. Edited by J. Y. Gillenwater, J. T. Grayhack, S.S. Howards andJ. W. Duckett. Chicago: Year Book Medical Publishers, vol. 2, chapt. 60, pp. 2001-2042, 1987. 13. Berdon, W. E., Baker, D. H. and Santulli, T. V.: Factors producing spurious obstruction of the inferior vena cava in infants and children with abdominal tumors. Radiology, 88: 111, 1967. 14. Slovis, T. L., Philippart, A. I., Cushing, B., Das, L., Perlmutter, A. D., Reed, J. 0., Wilner, H. I., Kroovand, R. L. and Farooki, Z. Q.: Evaluation of the inferior vena cava by sonography and venography in children with renal and hepatic tumors. Radiology, 140: 767, 1981. 15. Glazer, G. M., Callen, P. W. and Parker, J. J.: CT diagnosis of tumor thrombus in the inferior vena cava: avoiding the falsepositive diagnosis. Amer. J. Roentgen., 137: 1265, 1981. 16. Luck, S. R., DeLeon, S., Shkolnik, A., Morgan, E. and Labotka, R.: Intracardiac Wilms' tumor: diagnosis and management. J. Ped. Surg., 17: 551, 1982. 17. Kogan, S. J., Marans, H., Santorineau, M., Schneider, K., Reda, E. and Levitt, S. B.: Successful treatment of renal vein and vena caval extension of nephroblastoma by preoperative chemotherapy. J. Urol., 136: 312, 1986. 18. Wagget, J. and Koop, C. E.: Wilms' tumor: preoperative radiotherapy and chemotherapy in the management of massive tumors.

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RITCHEY AND ASSOCIATES

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