Wilms Tumor

• Wilms' tumor or nephroblastoma is malignant tumor of the kidneys that typically occurs in children. Dr. Max Wilms, the German surgeon (1867–1918) first described this kind of tumor.

• Wilms tumor is the fifth most common pediatric malignancy (7% of all childhood tumors).

• Incidence is 1 in 10,000, girls are slightly more affected

• 70% of cases occur before the child is 5 years of age.

• Most commonly unilateral, but in 5% - 10% both kidneys are involved.

• Approx 500 cases are diagnosed in the U.S. annually.

• The majority (75%) occurs in otherwise normal

children; a minority (25%) is associated with other developmental abnormalities.

• It is highly responsive to treatment, with about 90% of patients surviving at least five years.

Etiology

• Unknown

• Genetic abnormalities WT1 gene; dominant oncogene (at chromosome 11p13), WT2 gene (at chromosome 11p15)

It is believe that tumor begins to grow as a fetus develops in the womb, with some cells that are destined to form into the kidneys malfunctioning and forming a tumor.

The exact etiology of the tumor are still being investigated.

• Tumor is exceedingly vascular, soft, mushy, or gelatinous in character.

• Wilms tumor has capacity for rapid growth, usually grows to a large size.

• Tumor is usually uniform, well demarcated by a pseudocapsule of compressed renal tissue.

• Tumor develops from primitive renal tissue and can have epithelial ( tubules and glomeruli), stromal (fat, skeletal muscles, cartilage) and blastemal elements (An immature material from which cells and tissues develop).

Wilms tumor may be associated with

• Hemihypertrophy-one side of body is larger than other

• Aniridia (complete loss of iris) and

• Genitourinary anomalies.

Pathophysiology

• WT1 gene; dominant oncogene (at chromosome 11p13), WT2 gene (at chromosome 11p15)

(a tissue-specific gene for renal blastemal cells and glomerular epithelium)

• Leads to abnormal proliferation of the metanephric blastemal cells (primitive embryologic cells of the kidney).

• promote changes that may lead to the formation of Wilms tumor.

Clinical manifestations

• Wilms tumor is diagnosed at a mean age of 3.5 years.

• The most common feature is an upper quadrant abdominal mass (firm, nontender)

• Abdominal pain occurs in 30%-40% of cases, related to rapid growth of tumor.

• Urethral obstruction due to compression

• Constipation, vomiting, abdominal ditress, anorexia, weight loss and dyspnea due to enlargement of tumor.

• Other signs and symptoms of Wilms tumor include hypertension, fever caused by tumor necrosis, hematuria, and anemia.

• The neoplasm metastasize either by direct extension or by bloodstream. They may invade perirenal tissues, lymph nodes, the liver, the diaphragm, abdominal muscles and the lungs.

• Invasion of bone and brain are less common.

Diagnostic evaluation

Laboratory studies:• CBC with differential for baseline data• Platelet count:Coagulation abnormalities • Urinalysis for hematuria and urine culture• Liver function tests• Renal function tests• Blood chemistry; sr. electrolytes, uric acid

Imaging Studies

• Ultrasonography – Initial diagnosis of a renal or abdominal mass, – Possible renal vein or inferior vena cava (IVC)

thrombus (Doppler flow study may be helpful in the setting of vascular invasion.)

– Information regarding liver and other kidney

• CT scanning of the chest and abdomen – Differential diagnosis of a kidney tumor versus

adrenal tumor (neuroblastoma) – Liver metastases – Status of opposite kidney – Lymph node assessment – Status of chest with respect to metastases

• IVP

• Chest radiography - As a baseline for pulmonary metastases

• Bone scan

• Magnetic resonance imaging

Histologic Findings

• Favorable histology (90% of cases) is characterized by all 3 histological elements, without any anaplastic features. The cure rate in these cases is close to 90%.

• Unfavorable histology (10% of cases) is characterized by the presence of anaplasia.

• Anaplasia is defined as nuclear enlargement, and abnormal mitoses.

If tumor reveals sarcoma type of tumor then

• Bone scan

• Bone marrow aspirate

• Biopsy

Staging and treatment

• Staging is determined by combination of imaging studies and pathology findings.

• Treatment strategy is determined by the stage.

Stage I (43% of patients)• For stage I Wilms' tumor, 1 or more of the following

criteria must be met:• Tumor is limited to the kidney and is completely excised. • The surface of the renal capsule is intact. • The tumor is not ruptured or biopsied (open or needle)

prior to removal. • No involvement of extrarenal or renal sinus lymph-

vascular spaces • No residual tumor apparent beyond the margins of

excision. • Metastasis of tumor to lymph nodes not identified.

Treatment: • Nephrectomy +/- 18 weeks of

chemotherapy depending on age of patient and weight of tumor. EG: less than 2 years old and less than 550g only requires Nephrectomy with observation.

• Outcome: 98% 4-year survival; 85% 4-year survival if anaplastic

Stage II (23% of patients)For Stage II Wilms' tumor, 1 or more of the following criteria

must be met:• Tumor extends beyond the kidney but is completely

excised. • No residual tumor apparent at or beyond the margins of

excision. • Any of the following conditions may also exist:

– Tumor involvement of the blood vessels of the renal and/or outside the renal parenchyma.

– The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the flank.

– Extensive tumor involvement of renal soft tissue.

Treatment:

• Nephrectomy + abdominal radiation + 24 weeks of chemotherapy

• Outcome: 96% 4-year survival; 70% 4-year survival if anaplastic

Stage III (23% of patients)

For Stage III Wilms' tumor, 1 or more of the following criteria must be met:

• Unresectable primary tumor.

• Lymph node metastasis.

• Tumor is present at surgical margins.

• Tumor spillage involving peritoneal surfaces either before or during surgery.

Treatment:

• Abdominal radiation + 24 weeks of chemotherapy + nephrectomy after tumor shrinkage

• Outcome: 95% 4-year survival; 56% 4-year survival if anaplastic

Stage IV (10% of patients)

• Stage IV Wilms' tumor is defined as the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdomenopelvic region.

Treatment:

• Nephrectomy + abdominal radiation + 24 weeks of chemotherapy + radiation of metastatic site as appropriate.

• Outcome: 90% 4-year survival; 17% 4-year survival if anaplastic

Stage V (5% of patients)• Stage V Wilms’ tumor is defined as bilateral

renal involvement at the time of initial diagnosis.

• The 4-year survival in 94% patients with stage I or stage II; 76% for with stage III.

• Treatment: Individualized therapy based on tumor burden

Management

• Surgical ( partial/complete nephrectomy)

• Radiation therapy

• Chemotherapy

Chemotherapy

• Actinomycin D; 0.06 - 0.12 mg/kg, IV

• Doxorubicin ( adriamycin); 1.25 – 1.9 mg/ kg

• Vincristine; 0.125 – 0.05 mg/kg

• Stage I actinomycin and vincristine for 11-15 weeks

• Stage II actinomycin and vincristine for 15 months

• Stage III actinonycin, vincristine and adriamycin for 15 months,

• Stage IV actinomycin, vincristine, and adriamycin for 15 months. If response is slow then cyclophosphamide is added

• Stage V (bilateral wilms tumor)

1. Excision of tumor

2. If not possible, confirmatory biopsies then treated with vincristine and actinomycin D for 3-6 months. If no satisfactory resolution seen after 3 months, radiation is added to both kidneys

• A second look surgery is planned after 6 months of therapy, if not possible chemotherapy may be tried for an additional 9 months

• In totally inoperable cases with no metastatic disease bilateral nephrectomy and renal transplantation may be only viable operation.

Nursing Management