For pediatric surgery

1. Neuroblastoma

2. Introduction
– Neuroblastoma is the most common abdominal malignancy of childhood
• the most common cancer in infants.
– It arises in primitive precursors of the sympathetic nervous system and,
• consequently, occurs in the adrenal medulla and sites of sympathetic
ganglia not only in the abdomen but throughout the body.

3. – The annual incidence of neuroblastoma is about one case per 100 000 children,
• thereby,accounting for about 8% of all malignancies in those younger than 15 years
of age.
– However, neuroblastoma is responsible for approximately 15% of all pediatriccancer
deaths.
– The incidence of neuroblastoma is highest in very young children.

4. Complete resection of neuroblastoma offers definitive therapy
with a generally excellent outcome for most patients with localized disease,
 The role of surgery is even less clear in the curative treatment of
patients with high-risk neuroblastoma and
attempts at resection can be associated with significant complications.

5. Clinical presentation
– Patients with neuroblastoma usually present with signs and symptoms
• that reflect the primary site and extent of disease, although localized disease can be
asymptomatic.
– As 75% of neuroblastoma occurs in the abdominal cavity,
• an abdominal mass detected on physical examination is a common clinical feature, as is the
complaint of abdominal pain.
– Other primary sites of neuroblastoma include
• the posterior mediastinum (20%),
• the cervical region (1%), and the pelvis (4%) (organ of Zuckerkandel) .
• Respiratory distress or dysphagia may reflect a thoracic tumor

6. – Altered defecation or urination may be caused by
• mechanical compression from a pelvic tumor or
• by spinal cord compression from a paraspinal tumor.
• Spinal cord compression may also present as an altered gait.
– A tumor in the neck or upper thorax can produce
• Horner syndrome (ptosis, miosis, and anhydrosis), enophthalmos, and
• heterochromia of the iris.
• Acute cerebellar ataxia has also been observed, characterized by the dancing-eye
syndrome, which includes opsoclonus, myoclonus, and chaotic nystagmus.

8. • More than 40% of children with neuroblastoma have metastatic disease at
diagnosis.
– These patients are often quite ill and have systemic symptoms caused by
widespread disease.
• Neuroblastoma has a pattern of metastatic disease to the bone marrow,
lymph nodes, and bone.
– These metastases may manifest as anemia from marrow infiltration, or bone pain
and/or limp from cortical metastases.

9. • In very young patients, metastatic infiltration of the liver
– may result in hepatomegaly.
• Metastatic disease may be also associated with
– darkened eyes, referred to as“raccoon eyes,” resulting from retro-orbital
venous plexus spread, or purple, subcutaneous nodules, referred to as
“blueberry muffin” lesions.

10. • The diagnosis of neuroblastoma is generally made by
– histopathologic.
– Cross-sectional imaging (computed tomography (CT) or magnetic resonance imaging
(MRI)) together with 131I-metaiodobenzylguanidine (MIBG) scanning complete the initial
imaging workup.

13. Staging
– Staging systems are used to
• document disease extent and
• contribute to risk and treatment stratification.
– The most common such system used until recently has been
• the International Neuroblastoma Staging System (INSS).
– It is a surgicopathologicstaging system that depends on
• the completeness of resection of the primary tumor,
• assessment of ipsilateral and contralateral lymph nodes, and the relation of the
primary tumor to the midline.
– About 33% of patients have stage 1 or 2 disease,
– 60% have stage 3 or 4 disease, and
– about 7% present with stage 4S disease.

14.  aThe midline is defined as the vertebral
column.
 Tumors originating on one side and crossing
the midline must infiltrate to or beyond the
opposite side of the vertebral column.
 b Marrow involvement in stage 4S should be
minimal (i.e., <10% of total nucleated cells
identified as malignant on bone marrow
biopsy or on marrow aspirate).
 More extensive marrow involvement would
be considered to be stage 4.
 The metaiodobenzylguanidine scan (if
performed) should be negative in the marrow.

15. • Although INSS has been shown to have prognostic relevance,
– there have beensome difficulties with its widespread use.
• The expertise and aggressiveness of the surgeon influence tumor stage,
• lymph node sampling is done erratically, and
• patients who are simply observed without surgery cannot be appropriately staged.
• Therefore, a uniform, pre-treatment staging system that
– could be used easily throughout the world, and
– subject to real-time central review, was developed
• (International Neuroblastoma Risk Group Staging System (INRGSS)) based on
– tumor imaging rather than the extent of surgical resection.

16.  In this staging system, localized tumors are staged based on
 the absence (L1) or presence (L2) of one or more of 20 image-defined risk
factors (IDRFs,
 which generally regfect encasement of vital structures, primarily vessels and
nerves, as determined by diagnostic imaging studies, and
 which are associated with a lower complete resection rate and a greater risk
of surgery-related complications

19. Treatment
– The variables used for risk stratification in recent Children’s Oncology
Group (COG) clinical trials served to
• categorize infants and children with neuroblastoma in three risk groups
predictive of relapse:
– Low, intermediate, and high risk.
– The probability of prolonged disease-free survival for patients in each
group was >95%, >90%, and <30%, respectively.

21. • More recently, the INRG classification system is
– increasingly being used in which survival tree regression analyses
– with event-free survival (EFS) as the primary end point determined
– that seven prognostic variables could define 16 different pretreatment risk groups.
• these risk groups generate four categories based on expected 5-year EFS:
– Very low (>85% EFS, 28.2% of patients),
– low (>75 to ≤85% EFS, 26.8% of patients),
– intermediate (≥50 to 75% EFS, 9.0% of patients), and high (<50% EFS, 36.1% of
patients) risk.

22. Amp, amplified; GN, ganglioneuroma; GNB, ganglioneuroblastoma;
NA, not amplified.

23. • Low-Risk Disease:Surgery alone
– Resection is currently the only therapy given to patients with low-risk
disease, based on the prior experiences of each of the legacy groups
(POG and Children’s Cancer Group [CCG]).

24. • Intermediate-Risk Disease:Surgery + Chemo
– The most active agents against neuroblastoma: cyclophosphamide, doxorubicin,
carboplatin, and etoposide
– Four cycles (favorable biology) or eight cycles (unfavorable biology);
• cycles were given every 3 wks.
– The 3-year overall survival for the entire group was 96%.
– Radiation: symptomatic intermediate-risk patients when there is a risk of
impairment due to tumor bulk not responding to initial chemotherapy.

25. • High-risk Disease: multimodality
– Intensive induction chemotherapy
– Myeloablative consolidation therapy with stem cell rescue
– Targeted therapy for minimal residual disease
– Radiation therapy
– Surgery

26. • SURGERY
– Local disease:
• All patients with INSS stage 1 tumors,
• Stage 2A/2B tumors without MYCN amplification (and >50% resection)
• Stage 3 tumors of the midline that undergo gross total resection with negative
lymph node

27. Locoregional Disease:
• should receive neoadjuvant chemotherapy
– prior to attempted resection of the primary tumor and locoregional lymphadenopathy
• The role of surgery in the management of children with high-risk neuroblastoma is
controversial.
• Infants with stage 4 disease and MYCN-amplified tumors would benefit
– from more aggressive attempts at complete resection

28. Operative Principles
• Tumor size
• The extent of vascular encasement
• Exact tumor location should be considered in selecting the
approach for a retroperitoneal neuroblastoma

29. Operative Principles
1. Approach the operation as a vascular-type operation
2. The tumor should be removed piecemeal
3. Dissection commences distal to the lower edge of the tumor, generally along the
common or external iliac artery, and proceeds proximally

30. Operative Complications
• 80% of patients will experience significant blood loss that requires transfusion
• Up to 10% will suffer an injury to a major vascular structure
• In approximately 5% of cases, injury to other viscera (stomach, bowel, liver, spleen,
or kidney) occurs
• Wound complications occur is 1–5%, as does postoperative bowel obstruction.
• Hypertension, chyle leak into the thorax or abdomen, pleural effusion, infection and
sepsis, diarrhea can occur.