Wilms Tumor



Wilms Tumor


MARK D. TYSON

MICHAEL L. RITCHEY



Wilms tumor, or nephroblastoma, is the most common renal tumor of childhood, constituting approximately 6.3% of all cancers and 95% of all kidney cancers in children younger than the age of 15 years in the United States (1,2). According to the Surveillance, Epidemiology, and End-Results (SEER) registry, the average annual age-adjusted incidence rate of Wilms tumor is 8.0 per million, which translates into approximately 500 new cases in the United States per year (1). The incidence is highest among children younger than 2 years of age and declines precipitously with increasing age. The incidence rates are also somewhat higher for females and blacks (3,4).

Although most cases of Wilms tumor are sporadic, up to 10% of Wilms tumors are associated with overgrowth and non-overgrowth syndromes (5). Examples of overgrowth syndromes include Beckwith-Wiedemann syndrome, which is characterized by macroglossia, visceromegaly, and an omphalocele at birth, and is caused by microduplication mutations at 11p15.5. Other overgrowth syndromes include Simpson-Golabi-Behmel syndrome (an X-linked fetal overgrowth syndrome), Perlman syndrome (macrocephaly, macrosomia, visceromegaly, and dysmorphic facial features), and Sotos syndrome (cerebral gigantism). Examples of non-overgrowth syndromes include isolated aniridia, trisomy 18, WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation), Bloom syndrome (autosomal recessive disorder characterized by short stature, micrognathism, and café au lait spots), and Denys-Drash syndrome (male pseudohermaphrodism and mesangial renal sclerosis). Wilms tumor is also associated with isolated genitourinary anomalies such as hypospadias, cryptorchidism, and renal fusion.

The identification of the relationship between Wilms tumor and WAGR syndrome led to the discovery of genes associated with Wilms tumor. The WT1 gene located on chromosome 11p13 encodes a zinc finger transcriptional factor that serves both tumor-suppressive and developmental regulatory functions (5). Wild-type WT1 is critical in the early embryogenesis of the genitourinary system and is expressed in the kidneys, gonads, spleen, and mesothelium. The incidence of WT1 mutations in patients with nonsyndromal Wilms tumor is 2% (6). Another genetic mutation associated with Wilms tumor has been designated the WT2 gene, located at the chromosome 11p15 locus, which contains a cluster of imprinted genes. Loss of heterozygosity (LOH) at this locus is associated with Beckwith-Wiedemann syndrome.

LOH at chromosome 16q and/or 1p occurs in up to 20% of Wilms tumors (7). These have been shown to be associated with an increased risk for tumor relapse and mortality. In National Wilms Tumor Study (NWTS)-5, patients with stage I or II favorable-histology Wilms tumor (FHWT) and LOH of either 1p or 16q had an increased relative risk of relapse and death compared to patients lacking LOH at either locus. The risks of relapse and death for patients with stage III or IV FHWT were increased only with LOH for both regions.

Nephrogenic rests (NRs) are foci of primitive metanephric tissue that persist into infancy and are found in 1% of postmortem infant kidneys. Because NRs are found in up to 44% of kidneys removed for Wilms tumor and nearly 100% of patients with bilateral Wilms tumors, NR were thought to represent precursor lesions in children genetically predisposed to Wilms tumor. NRs are categorized as either perilobar or intralobar based on their anatomic location within the kidney. Perilobar NRs are observed in kidneys harboring Wilms tumors with WT2 locus deletions, whereas intralobar NRs are more often observed in those with WT1-associated tumors (8). The presence of multiple NRs in the nontumoral portion of a Wilms tumor kidney has been shown to be a risk factor for development of metachronous tumor in the contralateral kidney.




INDICATIONS FOR SURGERY

The survival metrics of children with Wilms tumor appear to be improving over time. According to the SEER registry, the relative 5-year survival rate for children younger than the age of 15 years has improved from 73.1% in 1975 to 93.6% in 2002 (2). This improvement in the long-term survival of children with Wilms tumor is a testament to the systematic approach from which multimodal therapy has evolved. Despite the advances in chemotherapy protocols and radiation techniques, a high-quality surgical operation remains paramount in the treatment of Wilms tumor. Primary radical nephrectomy is the procedure of choice for the majority of patients with unilateral Wilms tumor diagnosed in North America. Renalsparing surgery has been traditionally used in patients with bilateral Wilms tumors. However, the Children’s Oncology Group is now studying the role of renal-sparing surgery for select patients with unilateral tumors. Patients eligible for renal-sparing surgery on this protocol include those with a solitary kidney, a predisposition syndrome where tumors are found at a smaller size, and patients with an increased risk for developing renal failure (14,15). Several small single institution reports have documented the feasibility of partial nephrectomy in select cases of “low-risk” unilateral tumors, where nephron preservation is not imperative and where the risk of metachronous tumor formation is low (16). With respect to laparoscopy, there are reports in children with unilateral nonmetastatic Wilms tumor who received preoperative chemotherapy (17). However, the role of laparoscopy prior to chemotherapy may be limited because of large tumor size and risk of intraoperative spillage.

Tumor histology and stage are the most important determinants of prognosis in patients with Wilms tumor. Tumor grade, particularly the presence of anaplasia, is the most important prognostic factor and portends a poorer prognosis compared to favorable histology. The staging system used by the Children’s Oncology Group is presented in Table 85.1 and is based on various intraoperative and pathologic findings.


PREOPERATIVE CONSIDERATIONS

The International Society of Pediatric Oncology (SIOP) advocates preoperative chemotherapy for all patients with Wilms tumor regardless of the extent of disease (18). Preoperative treatment can produce dramatic reduction in the size of the primary tumor, facilitating surgical excision. The SIOP trials have demonstrated that the incidence of tumor rupture is lower after preoperative therapy. There is no survival advantage over a primary surgical approach. The Children’s Oncology Group (COG) recommends preoperative chemotherapy in children with bilateral tumors, tumors inoperable at surgical exploration, or IVC extension above the hepatic veins. All other patients are recommended to undergo primary excision of the tumor. This allows precise staging of patients with modulation of treatment for each individual, thereby decreasing the intensity of treatment when possible while maintaining excellent overall survival.








TABLE 85.1 STAGING SYSTEM OF THE CHILDREN’S ONCOLOGY GROUP





















Stage


Characteristics


I (45%)


The tumor is limited to the kidney and completely excised. The renal capsule is intact, and the tumor was not ruptured prior to removal. There is no residual tumor. The vessels of the renal sinus are not involved.


II (20%)


The tumor extends beyond the kidney but is completely excised. There is regional extension of the tumor (i.e., penetration of the renal capsule, extensive invasion of the renal sinus). Extrarenal vessels may contain tumor thrombus or be infiltrated by tumor. Lymph nodes do not contain cancer.


III (20%)


Residual nonhematogenous tumor confined to the abdomen: lymph node involvement, tumor spillage either before or during surgery, peritoneal implants, tumor beyond surgical margin either grossly or microscopically, or tumor not completely removed


IV (10%)


Hematogenous metastases (lung, liver, bone, brain, etc.) or lymph node metastases outside the abdominopelvic region are present.


V


(5%) Bilateral renal involvement at diagnosis



SURGICAL TECHNIQUE

The recommended surgical approach for Wilms tumor is through a transperitoneal transabdominal incision. An extraperitoneal flank incision should be avoided because it does not allow for proper staging. A generous transverse abdominal incision allows for inspection and exploration of the abdominal cavity. The patient is placed in a supine position with mild flexion of the lumbar spine to facilitate the exposure of retroperitoneal structures. The incision is made approximately two fingerbreadths above the umbilicus beginning in the midaxillary line on the side of the neoplasm. The extent to which the incision is extended across the midline will vary with the size of the tumor and amount of exposure needed. The incision may be extended into a thoracoabdominal approach by continuing through the bed of the 9th or 10th rib, if necessary. The muscle layers are divided sequentially to facilitate exposure. The peritoneal space should be opened carefully.
The tumor may compress the colon and/or small bowel against the anterior abdominal wall, inadvertently resulting in enterotomy. A thorough exploration of the abdomen is performed. The peritoneal cavity is assessed for evidence of preoperative tumor rupture and peritoneal implants. The liver is carefully examined, as liver metastases may not be identified on preoperative imaging studies. An assessment of tumor extent is performed next, including palpation of the IVC and assessment of regional lymphadenopathy, perinephric extension, and tumor mobility. Formal exploration of the contralateral kidney is not needed if preoperative imaging does not demonstrate bilateral lesions (19).

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Apr 24, 2020 | Posted by in UROLOGY | Comments Off on Wilms Tumor

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