Douglas C. Barnhart
Presentation
A 15-month-old boy who was born prematurely at 28 weeks’ gestation is growing and developing normally. He has no other medical problems or long-term sequelae of prematurity. While giving him a bath, his mother notes a large mass that seems to be left sided. He is examined by his pediatrician who confirms the presence of large abdominal mass that is not tender. His vital signs including blood pressure are normal. Routine laboratories including a CBC and urinalysis are normal.
Differential Diagnosis
The sudden recognition of a large abdominal mass in an infant or a young child is not an uncommon occurrence and is the typical presentation for most intra-abdominal malignancies in this age group. These masses are often very large at presentation and are typically nontender and apparently asymptomatic. The most common malignancies of early childhood, which present with large abdominal masses, are Wilm’s tumor (nephroblastoma), neuroblastoma, and hepatoblastoma. Less common primary pediatric renal tumors include congenital mesoblastic nephroma (infants < 6 months), clear cell sarcoma, rhabdoid tumor, and renal carcinoma. Rhabdomyosarcoma may also present with a large abdominal mass although this is more typically located in the pelvis as it often arises from the genitourinary tract. Less common abdominal malignancies in a young child are germ cell tumors and lymphoma.
It is important to recognize that not all palpable abdominal lesions in the young child are malignancies, however. Massive hydronephrosis can present with a large unilateral abdominal mass. It would be common though for these to be detected on prenatal ultrasound. Autosomal dominant polycystic kidney disease can present with bilaterally enlarged kidneys that may be palpable on physical examination. Large omental cysts, duplication cysts of the gastrointestinal tract, lymphatic malformations, and ovarian cysts may also present with abdominal fullness and possibly a palpable mass.
Workup
Given the lifelong risk of malignancy associated with radiation exposure in children, CT scans should be used judiciously. Abdominal ultrasound is the preferred initial study in a child presenting with a palpable abdominal mass. Most of the benign diagnoses can be made with the use of ultrasound alone. Patients with hydronephrosis, polycystic kidney disease, and ovarian cysts are likely not to require a CT scan for diagnosis and management. Children with solid or mixed (solid and cystic) lesions on ultrasound should undergo a CT scan with oral and intravenous contrast to characterize the organ of origin and anatomic extent of the mass. In some cases, it can be difficult to discern if a large tumor is arising from the liver (hepatoblastoma), adrenal gland (neuroblastoma), or kidney (Wilm’s tumor).
Presentation Continued
The patient underwent a contrast CT scan that demonstrated a 7-cm mass arising from the left kidney. The CT scan demonstrated a “claw sign” in which the remaining renal parenchyma encircles the mass (Figure 1). This suggests a primary renal tumor even if the mass abuts and displaces the liver and the adrenal gland is not visualized. As Wilm’s tumor can occur bilaterally (5% of all chil dren with Wilm’s tumors), it is important to assure that the contralateral kidney is normal. The CT scan often demonstrates compression of the inferior vena cava (IVC) by the mass. Wilm’s tumor is prone to develop tumor thrombi, which can extend into the vena cava and even the right atrium. A Doppler ultrasound is typically obtained to evaluate the renal vein and the IVC. The lungs and liver are the most common sites of distant metastases. A chest CT is therefore obtained as part of the preoperative staging evaluation. The child’s ultrasound demon strated no signs of tumor thrombus in the IVC, and there were no distant metastases.
FIGURE 1 • The child’s CT scan demonstrates a large solitary mass involving the left kidney. The renal parenchyma is displaced by the tumor. This “claw sign” is seen more clearly on the coronal images. The right kidney is normal. There was no evidence of hepatic or pulmonary metastases.
Diagnosisand Treatment
Based on the age at presentation and appearance on CT scan, this toddler is presumed to have a Wilm’s tumor and should be managed accordingly. The treatment of Wilm’s tumor is multimodality and has been well defined initially through the National Wilm’s Tumor Study and subsequently through Children’s Oncology Group trials in North America. Similar organizations in Europe (SIOP–International Society of Paediatric Oncology) and the United Kingdom have conducted clinical trials as well. Essentially, all children are treated with surgical resection and chemotherapy. Radiation therapy is used to treat pulmonary metastases and selectively to enhance intra-abdominal local control. There are fundamental differences between North America and Europe in the approach to Wilm’s tumor. The American approach favors upfront resection to provide immediate local control and accurate staging. This strategy may potentially diminish the required chemotherapy. The European strategy treats with chemotherapy presumptively without biopsy or initial resection in many cases. This strategy simplifies resection as there is often a dramatic response to chemotherapy. This may decrease the rate of intraoperative tumor rupture but confound accurate staging as lymph node status prior to treatment is unknown. The remainder of this discussion will focus on the American approach. All children with Wilm’s tumor should be treated in a center with a multidisciplinary team.
Survival in children with Wilm’s tumor is principally determined by the stage at presentation and the presence of diffuse anaplasia (Table 1). More recent studies suggest that loss of genetic material at 1p and 16q may also be associated poorer outcomes. Children with favorable histology (lack of anaplasia) and lower stages (I–II) have excellent outcomes with standard two-drug chemotherapy (vincristine and dactinomycin). Typical therapy for children with higher stages of favorable histology Wilm’s tumors adds a third drug such as doxorubicin. Children with favorable histology do well with even stage IV patients having overall survival near 90%. Anaplasia is associated with resistance to chemotherapy. These children do more poorly with overall survival in stage IV patients approximately 50%. Due to the markedly decreased survival associated with this histology, adjunctive chemotherapy regimens for these patients remain an active area of research.
TABLE 1. Wilm’s Tumor Staging
Abdominal radiation therapy is used to improve local control in patients with local stage III disease. Wholelung radiation is standard therapy for children with pulmonary metastases, but current research is directed to see whether this can be eliminated in those who have complete response to a more intensive chemotherapy regimen. Management of children with bilateral Wilm’s tumors (stage V) requires preservation of renal function, while not jeopardizing oncologic cure. Decisions regarding biopsy and resection in these complicated children must be done as part of multidisciplinary approach and are beyond the scope of this discussion.
Decisions regarding local control are made independently of the presence of distant metastases. The three principal goals of laparotomy for Wilm’s tumor are to (1) obtain accurate diagnosis and staging, (2) resect the primary tumor without causing local upstaging (i.e., tumor spillage), and (3) avoid resection of adjacent organs. Many Wilm’s tumors present as very large masses, and size per se should not be considered a contraindication to upfront resection. Contraindications to initial resection include extensive venous tumor thrombus and invasion of adjacent organs. Tumor thrombus in Wilm’s tumor can be extensive with involvement of the retrohepatic IVC and the right atrium. In such cases, operative biopsy and pre-resection chemotherapy are recommended as they typically reduce the thrombus facilitating resection. Tumor thrombus in the renal vein and infrahepatic vena cava can typically be extracted after obtaining vascular control of the IVC. The extent of tumor thrombus can be accurately characterized preoperatively using CT scan and ultrasound. In contrast, extension to adjacent organs can often not be determined preoperatively. With the exception of the adrenal gland, other involved organs should not be resected as a part of the initial operation. Rather in such cases, an operative biopsy should be performed and nephrectomy deferred until chemotherapy is given.
Surgical Approach
Given the large size and fragility of Wilm’s tumors, generous exposure is required to avoid tumor rupture during resection. The importance of this cannot be overstated as tumor rupture will necessitate abdominal radiation even if the child was stage I or II preoperatively. Additionally, the large size of the mass frequently distorts relationships with adjacent visceral vessels making exposure essential for protection of the mesenteric and the contralateral renal vessels. The ureter must be resected with an adequate margin to assure that it is free of tumor. Finally, proper staging must include aortocaval lymph node sampling and inspection of the peritoneal surfaces.
In order to accomplish these goals, a generous transverse laparotomy is typically performed (Table 2). For large right-sided tumors, a thoracoabdominal exposure may facilitate vascular control and mobilization of the tumor. A retroperitoneal, flank approach is not appropriate due to the large size of these tumors and the clinical significance of an intraoperative rupture. Laparoscopic resection is not appropriate for upfront resection but is being explored using the European approach of delayed resection after preoperative chemotherapy.
TABLE 2. Key Technical Steps and Potential Pitfalls
Upon entry into the peritoneal cavity, inspection and palpation is performed for staging, and all findings are documented. Any bloody fluid in the peritoneum is recorded and collected. The peritoneum is inspected for tumor implants. Either of these findings would suggest preoperative tumor rupture. The liver is inspected and palpated although most lesions would be identified on preoperative imaging. In the past, the contralateral kidney was exposed, inspected, and palpated on both the anterior and the posterior surfaces. This maneuver placed this typically normal and soon-to-be solitary kidney at risk of injury. Given the accuracy of current CT scans, this is not necessary and should be avoided. If there is no obvious invasion of adjacent organs on this initial examination, it is appropriate to begin mobilization for nephrectomy. In the case of obvious invasion of other organs, a wedge biopsy should be performed. A generous biopsy should be obtained as core needle biopsies may fail to detect anaplasia. Any type of biopsy is considered to cause rupture of the tumor and results in upstaging of the tumor (stage III). Therefore, a tumor that can be resected should not be biopsied simply to confirm the diagnosis prior to resection.
After resection is decided upon, the peritoneal reflection of the ipsilateral portion of the colon is divided to allow the colon to be mobilized medially. The duodenum is similarly mobilized to allow exposure of the renal hilum, IVC, and aorta. If the aorta can be exposed initially, the renal artery should be isolated and divided after mobilization and retraction of the renal vein. This is followed by ligation of the vein. In most cases, however, the tumor is sufficiently large that the IVC and the aorta will be obscured. In these cases, initial mobilization of the tumor will be required to allow access to the aorta and the IVC.
The tumor is mobilized typically in a gradual circumferential fashion. It is common for there to be neovascularity from the retroperitoneum. Vessel-sealing devices are helpful in this mobilization. Careful attention must be paid to avoid traction on the mass as the tumor capsule is easily disrupted resulting spillage of tumor. If the ipsilateral adrenal gland is adherent to the tumor, it should be resected along with the nephrectomy specimen. No attempt to separate the adrenal gland should be made if this may increase the risk of tumor rupture. As the nephrectomy specimen is circumferentially mobilized, the ureter will become apparent. The ureter should be dissected distally to allow resection en bloc with the nephrectomy specimen. The ureter is divided as distally as possible, but it is unnecessary to resect a cuff of bladder. Mobilization of the tumor allows it to be rolled medially to provide posterior exposure of the renal artery. Duplicated renal arteries are common and should be sought. Dissection of the renal vein allows it to be retracted to provide anterior exposure of the renal artery was well. With left-sided tumors, the gonadal vein may be divided to facilitate this exposure.
Ideally, the artery is ligated prior to division of the renal vein to avoid engorgement of the tumor. There can be marked distortion of the mesenteric and the contralateral renal vessels with large Wilm’s tumors, so it is essential to achieve adequate exposure of the aorta to verify the anatomy prior to ligation of the purported renal artery. The renal vein should be palpated for tumor thrombus prior to ligation. If there is tumor thrombus present, proximal and distal control of the IVC must be obtained so that renal vein/IVC junction can be opened for a tumor thrombectomy. Typically, the tumor thrombus is not densely adherent and can be withdrawn through the venotomy with forceps. Division of the renal vessels and ureter provides access to any remaining retroperitoneal attachments that can be divided with electrocautery to complete the nephrectomy.
The nephrectomy specimen should be sent intact to pathology. As an important part of the pathologic staging of Wilm’s tumor is a systematic microscopic examination of inked margins, bivalving the specimen in the operating room is contraindicated.
After removal of the nephrectomy specimen, the aorta and IVC are clearly visible allowing aortocaval lymph node sampling. As 41% of stage III tumors are due to lymph node involvement only, this node sampling is essential to correct staging. All visible aortocaval lymph nodes are removed, but it is not necessary to perform a formal lymph node dissection that may be associated with increased morbidity. Hemostasis is verified and lymphatic leaks sought prior to closure of the laparotomy.
Consideration should be given to placing a subcutaneous venous access port at the time of nephrectomy. This should be decided in discussion with the pediatric medical oncologist as some children with stage I tumors may be successfully managed with only a peripherally inserted central catheter. Additionally, a current study is investigating whether chemotherapy may be safely eliminated in infants with stage I smaller tumors. All others can typically be treated with a single lumen central venous access device.
Postoperative Care
Children may be admitted to the acute care floor or intensive care dependent upon local practice with particular attention to assuring adequate analgesia and fluid resuscitation. Many children will benefit from epidural analgesia if it is available. It is essential to assure adequate intravascular volume to provide perfusion to the now solitary kidney, and urine output should be carefully monitored typically with a Foley catheter. Most children’s postoperative ileus is relatively brief (2 to 4 days) and nasogastric decompression is not routinely required. Small bowel: small bowel intussusception can occur in the immediate postoperative period in children who underwent resection of retroperitoneal tumors. This should be sought if the child seems to have a prolonged postoperative ileus or an immediate postoperative bowel obstruction.
Chemotherapy is typically initiated prior to discharge home from the operation (usually by postoperative day 5). After completion of chemotherapy and possible radiation therapy, surveillance is performed using chest and abdominal CT scans. Local recurrences in the renal bed are managed with resection and radiation in addition to chemotherapy.
Case Conclusion
The boy undergoes a laparotomy and is found to have an intact tumor capsule without evidence of metastatic disease. A tumor nephrectomy is performed without spillage. There was no involvement of the renal vein. Final pathology showed stage I favorable histology Wilm’s tumor. He was treated with a standard course of vincristine and dactinomycin and is currently in remission.
TAKE HOME POINTS
· Wilm’s tumor is the most common renal tumor in children. Renal masses in children are managed presumptively as Wilm’s tumor.
· Outcomes are dependent on the stage and the presence or absence of diffuse anaplasia.
· Decisions about local control via nephrectomy are independent of hematogenous metastases.
· Preoperative or intraoperative biopsy should be avoided to not upstage tumor and mandate abdominal radiation.
· Primary resection of the tumor should be performed avoiding disruption of the tumor capsule or resection of adjacent organs.
· Aortocaval lymph node sampling is essential for accurate staging.
· Adjunctive chemotherapy is routine, while radiotherapy is used to supplement local control in stage III tumors and for pulmonary metastases.
SUGGESTED READING
Davidoff AM. Wilm’s tumor. Curr Opin Pediatr. 2009;21(3): 357–364.
Ehrlich PF. Wilm’s tumor: progress and considerations for the surgeon. Surg Oncol. 2007;16(3):157–171.