Author’s Accepted Manuscript

Complications in the surgical management of

children with malignant solid tumors

Andrew M. Davidoff, Israel Fernandez-Pineda

www.elsevier.com/locate/sempedsurg

PII: S1055-8586(16)30053-1
DOI: http://dx.doi.org/10.1053/j.sempedsurg.2016.10.003
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To appear in: Seminars in Pediatric Surgery
Cite this article as: Andrew M. Davidoff and Israel Fernandez-Pineda,
Complications in the surgical management of children with malignant solid
t u m o r s , Seminars in Pediatric Surgery,
http://dx.doi.org/10.1053/j.sempedsurg.2016.10.003
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 Complications in the surgical management of children with malignant
solid tumors

Andrew M. Davidoff, MD and Israel Fernandez-Pineda, MD

From the Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN

Address correspondence to:

Andrew M. Davidoff, MD
Department of Surgery
St. Jude Children’s Research Hospital,
262 Danny Thomas Place
Memphis, TN 38105-3678
email: andrew.davidoff@stjude.org
 2

Abstract

With improvement in the outcomes for children with cancer has come an increasing focus

on minimizing the morbidity from therapeutic interventions, including surgical procedures, while

continuing to have a high likelihood of cure. Thus, an appreciation for the potential

complications of surgery, both acute and long term, is critical when considering the risks and

benefits of any procedure performed on a child with cancer. Although not meant to be an

exhaustive review, here we discuss the most common and significant surgical complications that

may occur when performing diagnostic, therapeutic or supportive procedures in children with the

most common malignant solid tumors.

Keywords: pediatric cancer; surgery, complications, neuroblastoma, Wilms tumor,

sarcoma
 3

Significant improvement has been made in the outcome for children with cancer over the

past 60 years with overall survival increasing from about 30% to currently over 80%.1 Surgery

plays a critical role in the management of pediatric patients with cancer, particularly those with

solid tumors. In addition to achieving a good oncologic outcome, however, attention is

increasingly being paid to the morbidity and complications, both acute and long term, associated

with each of the various modalities used to effect cure, including surgery. As survival has

improved, there is now greater opportunity to appreciate long term complications of therapy.

Pediatric surgeons play a critical role in diagnosing, staging and treating children with

solid malignant tumors. Therefore, it is imperative for the pediatric surgeon, as a member of the

multidisciplinary team involved in the care of these patients, to understand the indications for

and implications of surgery in their treatment and the risks and benefits of any surgical

procedure. Here we review the most common and significant surgical complications that can

occur with different operations. Generic complications such as bleeding, infection, poor wound

healing and complications related to anesthesia will not be discussed in detail here.

NEUROBLASTOMA RESECTION

Neuroblastoma is a malignancy of the sympathetic nervous system and is a

heterogeneous disease; tumors can spontaneously regress or mature or display an aggressive,

therapy-resistant phenotype. Complete resection of a localized neuroblastoma with favorable

biology offers definitive therapy with generally excellent outcome; although, the value of

complete tumor removal may be overestimated because of the possibility that localized

neuroblastomas may not require any therapy, including resection. The role of surgery is even less

clear in the curative treatment of patients with high risk, metastatic neuroblastoma,2 although a
 4

recent review of the Children’s Oncology Group (COG) experience suggests that ≥90% resection

of the primary and regional disease is associated with significantly better event free survival and

a lower cumulative incidence of local progression.3 However, overall survival in this study was

not significantly impacted. Additionally, it has long been recognized that neuroblastoma

resection, in part because of its frequently infiltrative growth pattern, can be associated with a

high complication rate.4-7 Thus, it is crucial that surgeons consider the heterogeneous nature of

neuroblastoma and the molecular and biologic characteristics associated with good or bad

prognoses as well as the potential complications associated with neuroblastoma resection when

determining the role of surgery in any specific case.8 An illustrative example is the very

favorable overall outcome for infants with metastatic, single-copy MYCN disease, regardless of

the extent of surgery.9 Clearly, the excellent prognosis for these patients should not be

jeopardized by overly aggressive surgery that may lead to significant morbidity or even

mortality.

Vascular injury

Intra-abdominal neuroblastoma, particularly with unfavorable biology, has a propensity

for encasing visceral vessels. As a consequence, up to 10% of patients will suffer an injury to a

major vascular structure during attempts at surgical resection. A critical step for avoiding injury

to these vessels is their identification before they pass through the tumor, most often at their take

off from the aorta or vena cava. This should be done as early as possible in the course of an

operation. The tumor is then removed piecemeal after freeing the circumference of the artery. It

is very difficult to identify the artery by simply dissecting into the middle of the tumor and this

approach should be avoided. Even with meticulous dissection, significant blood loss and

resultant transfusion requirement is common after resection of high risk neuroblastoma.

 5

Neurologic injury

Extension of neuroblastoma through neural foramina and into the spinal column is a

fairly common occurrence, especially with paraspinal and thoracic primaries, occurring in 7-15%

of cases with half being symptommatic.10 In general, there is rarely an indication to remove the

tumor extension surgically as the risks of resecting this residual disease appear to outweigh the

benefits. Patients with favorable clinical characteristics and tumor biology have an excellent

oncologic and neurologic prognosis despite leaving some gross residual disease in the neural

foramina and spinal column. Patients with unfavorable clinical characteristics and tumor biology

will receive intensive multimodality therapy which is a critical component of successful

treatment. Complications of aggressive surgery can include the development of an intraspinal

hematoma and cord compression or direct injury to nerves which may result in deficits including

sciatic nerve palsy, urinary and fecal incontinence, neurogenic bladder, erectile dysfunction, leg

weakness or nerve root injury. Nevertheless, tumor extension into the neural foramen and spinal

canal that causes acute neurologic deterioration may be most appropriately treated by emergent

surgical resection via laminotomy.10

Ischemia of the cord can occur following resection of a paraspinal neuroblastoma,

particularly inferiorly located posterior mediastinal tumors. This is due to injury to the artery of

Adamkiewicz, an artery that arises off the aorta, typically at the level of 9-12th left posterior

intercostal artery but whose origin can be variable, and which serves as the main blood supply to

the spinal cord. Because of this, some authors have suggested the use of preoperative spinal

angiography and intraoperative cord monitoring in certain circumstances, as they may guide the

conduct of tumor resection, to avoid injury to this critical artery.11

 6

Kidney loss

Every effort should be made to avoid nephrectomy when resecting a retroperitoneal

neuroblastoma. Patients with favorable clinical characteristics and tumor biology generally have

an excellent outcome regardless of the completeness of resection while patients with unfavorable

clinical characteristics and tumor biology need intensive multimodality therapy for which normal

renal function is required in order to receive the full recommended doses. Nevertheless, for this

later group, some perform nephrectomy when it is required to achieve complete tumor resection,

at reported rates of 5-10%.12,13 The benefit of this, when considering the impact on renal function

and ability to tolerate high dose chemotherapy is uncertain.

Because neuroblastoma often grows into the renal hilum encasing the renal vessels,

kidney loss due to ischemia is not an uncommon occurrence, particularly in patients with high

risk disease. This complication occurs due to injury to the renal vasculature rather than to the

kidney itself. This can be due to inadvertent ligation and division of the renal artery or vein,

injury to either of these vessels that cannot be successfully repaired, or trauma to the artery from

torque that results in spasm and renal ischemia. The later may result in a “disappearing kidney,”

a term that refers to atrophy of a kidney likely due to vascular injury at the time of surgery.

However, the consequence of this traumatic injury is generally not noted until later in a patient’s

clinical course, often months later, when follow-up imaging demonstrates a diminutive or

completely absent kidney. The exact etiology for this complication is not well understood but is

believed to involve spasm and/or intimal disruption of the renal artery due to excessive

manipulation, particularly torque, on the vessel when trying to expose and resect

lymphadenopathy from behind the renal vein. Thus, great care must be taken when removing

tumor from around the renal vessels not to apply torque to the artery while retracting the tumor
 7

mass. Some advocate systemic renal dose dopamine or intramural lidocaine in an attempt to

prevent or break the spasm of the artery.14

Extensive associated lymphadenopathy may also encase the ipsilateral ureter putting it at

risk for injury during resection of extensive retroperitoneal disease. As mentioned previously

when discussing avoidance of vascular injury, it is also important to identify the ureter before it

passes through the involved lymph nodes. Additionally, preoperative placement of a ureteral

stent may facilitate identification of the ureter and avoidance of injury.

Occasionally neuroblastoma may invade the kidney, potentially leading to the

misdiagnosis of Wilms tumor at presentation.15 Distinguishing these tumor types is critical as the

surgical management for neuroblastoma and Wilms tumor differs significantly. The presence of

constitutional symptoms, intratumoral calcification or vascular encasement on preoperative

imaging should heighten suspicion for neuroblastoma. In addition, laboratory evaluation,

including urinary catecholamines and radiographic studies, such as MIBG, should be completed

prior to surgery when the etiology of an abdominal tumor is uncertain.

Chylous ascites/chylothorax

Postoperative chyle leak is a well-recognized complication of neuroblastoma surgery that

results from disruption of either mediastinal or retroperitoneal lymphatic channels during tumor

resection. Neuroblastoma often has an infiltrative growth pattern around major vessels where

lymphatics are also residing making them susceptible to injury or disruption when performing a

perivascular dissection. Nonsurgical treatment is effective for most patient with chyle leak.

Management includes fasting to reduce lymph flow often requiring the use of total parental

nutrition. Drainage via tube thoracostomy or paracentesis may be required to alleviate

 8

compressive symptoms. Most patients respond to conservative management within 1-2 months

although some will require operative intervention for failure of conservative management.

Surgical options include primary direct surgical repair, fibrin glue application, embolization or

establishment of a peritoneovenous shunt. However, the exact duration that conservative therapy

should be tried before surgical treatment is controversial as early ligation of the leakage site may

be helpful in avoiding metabolic complications, delay in adjuvant therapy and prolonged

hospitalization.16

Diarrhea

After resection of advanced abdominal neuroblastoma children may have persistent

diarrhea, perhaps resulting from disruption of the autonomic nerve supply to the gut during

clearance of tumor from the major vessels of the retroperitoneum. In one series, 30% of patients

had postoperative diarrhea.17 Dissection around the superior mesenteric and celiac arteries was

associated with a significantly higher incidence of diarrhea. Patients such as these may require

long term treatment with medication to slow intestinal peristalsis and a few will have severe and

unremitting diarrhea. The authors of that series hypothesized that (1) attenuation of inhibition of

peristalsis resulting from disruption of the sympathetic nerve supply, (2) bile acid and fat

malabsorption as a result of bacterial overgrowth in stagnant bowel loops caused by damage to

the parasympathetic supply and (3) disturbance in gut hormone activity caused by disruption of

autonomic fibers all may contribute to the development of diarrhea.

Horner syndrome

Horner syndrome, consisting of miosis (decreased pupil size), ptosis (drooping eyelid),

and anhidrosis (decreased sweating on the ipsilateral side of the face) can be caused by
 9

disruption or trauma to the stellate ganglion which is located at apex of the chest. This

constellation of symptoms may be due to the presence of an apical thoracic tumor such as

neuroblastoma and may, in fact, be the presenting symptom or may occur as a consequence of

resection of an apical neuroblastoma with iatrogenic disruption during the course of tumor

dissection. Because of this potential complication, which may be permanent, this possible

outcome should be discussed with parents prior to surgery for an upper mediastinal

neuroblastoma after it has been determined that resection is critical for cure.

Image-defined risk factors (IDRFs)

One way to anticipate the likelihood of complications following surgical resection of

neuroblastoma is by assessing the presence or absence of image-defined surgical risk factors on

preoperative imaging. IDRFs are listed in Table 1 and generally reflect encasement of vital

structures, primarily vessels and nerves, as determined by diagnostic imaging studies. Cecchetto

et al, reported that the presence of one or more of these image-defined surgical risk factors was

associated with a greater risk of surgery related complications and a lower complete resection

rate when attempting an initial resection of a localized neuroblastoma.18 In 534 patients with

localized, non-MYCN amplified neuroblastoma studied there was a 17% operative complication

rate in patients with one or more IDRFs (L2), a rate significantly higher than the 5% incidence in

patients without an IDRF (L1) patients.18 Surgery related complications occurred more often in

the neck compared with the thorax and abdomen (33.3% v 10.8% v 6.0%).

Bowel obstruction

Although not unique to neuroblastoma resection, a potential long term complication

common to all abdominal operations is intestinal obstruction. Madenci et al,19 evaluated the
 10

occurrence of intestinal obstruction requiring surgery occurring 5 or more years after cancer

diagnosis in 12,316 5-year survivors in the Childhood Cancer Survivor Study. Late obstruction

was reported by 165 survivors (median time from diagnosis, 13 years). The cumulative incidence

of late obstruction at 35 years was 5.8% among survivors with abdominopelvic tumors.

Treatment with abdominopelvic radiotherapy within 5 years of cancer diagnosis increased the

rate of late obstruction. Importantly, the development of late obstruction increased subsequent

mortality among survivors.

WILMS TUMOR RESECTION

Wilms tumor accounts for nearly six percent of all pediatric cancers and more than 95

percent of all kidney tumors in children. Fortunately, the outcome for patients with Wilms tumor

is generally excellent with overall survival being greater than 90%. The role of surgery in the

therapy of Wilms tumor is paramount since a meticulous and well performed procedure will

accurately determine the stage of the patient and their future therapy and give the patient the best

chance for cure.

Review of sequential National Wilms Tumor Studies (NWTS) revealed an overall

incidence of surgical complications of 19.8% and 12.7% in NWTS-3 and NWTS-4, respectively.

In NWTS-3,20 the most common complication was intestinal obstruction which occurred in

almost 7% of patients. This was followed by extensive intraoperative hemorrhage (6%) defined

as blood loss exceeding 50cc/kg. Intraoperative injuries to other visceral organs (including

intestine, liver and spleen) and vascular structures occurred in about 2% of cases. Death

attributed to surgical complications occurred in 0.5% of the cases only one of which was

intraoperative. Factors associated with the occurrence of surgical complications included

 11

advanced local tumor stage at diagnosis, intravascular tumor extension and resection of other

visceral organs at the time of nephrectomy. In NWTS-4,21 intestinal obstruction was again the

most common complication (5.1%), followed by extensive hemorrhage (1.9%), wound infection

(1.9%) and vascular injury (1.5%). Intravascular extension into the inferior vena cava or atrium

and nephrectomy performed through a flank or paramedian incision were both associated with

increased risk of complications. Tumor diameter greater than or equal to 10cm was also

associated with an increased risk of surgical complications. Also, the risk of complications was

higher if the nephrectomy was performed by a general surgeon rather than a pediatric surgeon or

pediatric urologist.

Tumor spill

The COG recommends primary nephroureterectomy with lymph node sampling as the

initial management of a renal mass likely to be Wilms tumor. While this provides accurate

staging and immediate histology to define further treatment, it does result in a rate of

intraoperative spill of approximately 10% with tumor size being significantly associated with

tumor spill.22 Meticulous dissection of the tumor through an ample incision is important.

Avoiding tumor spill is critical as spillage will result in upstaging the patient’s disease with

subsequent intensification of adjuvant therapy including doxorubicin and ionizing radiation.

Despite this intensification of therapy, one of the largest relative risks for local recurrence is still

tumor spillage during surgery and survival of children after local recurrence is poor with an

average two-year survival 2 years after relapse of 43%.23 Biopsy of a primary tumor should not

be performed just prior to removal as this will also upstage the patient and lead to a higher rate of

local recurrence. A partial nephrectomy or a laparoscopic approach to partial or radical

 12

nephrectomy is also discouraged by the COG because of the potential for tumor spill or positive

margins.24

One approach to reducing the rate of intraoperative spill is through prenephrectomy

chemotherapy, an approach that has long been used by the Société Internationale d’Oncologie

Pédiatrique (SIOP). SIOP studies have reported a lower intraoperative tumor spill rate of 2.8–

6%.25,26 It is believed that primary chemotherapy makes subsequent surgical extirpation easier

due to tumor shrinkage and decreased vascularity resulting in a smaller, firmer tumor, although

the ability to determine locoregional lymph node involvement and early identification of

histologies other than favorable histology Wilms tumor may be lost.

Vascular injury

Iatrogenic injury to the aorta or its major branches during nephrectomy for Wilms tumor

in children is a rare but significant complication. One study identified four patients with ligation

of the superior mesenteric artery that occurred during nephrectomy.27 Of note, each of these

cases occurred with left sided tumors. In addition to generally being aware of the possibly

distorted vascular anatomy when resecting large Wilms tumors, surgeons should give strong

consideration to completely mobilizing the tumor so that only the vascular pedicle remains as an

attachment to ensure the renal vessels can be clearly identified before their ligation. Early vessel

ligation is discouraged and should not be done until the renal vasculature had been clearly

identified.
 13

Intussusception

Postoperative intussusception is a rare complication after a variety of operations but has

an estimated incidence of 0.01–0.25 % in children following laparotomy, particularly for

resection of a retroperitoneal tumor such as Wilms.28-30 Early recognition in the postoperative

period may be difficult because feeding intolerance may be attributed to postoperative ileus. Side

effects of chemotherapy may also obscure the diagnosis.31 However, delayed identification and

management may result in significant morbidity and so a high index of suspicion should be

maintained, particularly if oral intake had been tolerated initially after surgery. Ultrasound may

be a useful study as the intussusception is most often ileoileal. The etiology of postoperative

intussusception is unclear. The theories to explain mechanisms include altered peristalsis, early

postoperative adhesions, prolonged and excessive bowel manipulation, electrolyte disturbances

in lengthy surgeries, anesthetic drugs, opioid analgesics and neurogenic factors.32 Postoperative

small bowel obstruction occurred in 131 of 1,910 children (6.9%) enrolled in NWTS-3. The

etiology of the small bowel obstruction was bowel adhesions in 104 cases, intussusception in 17,

internal hernia in 2 and uncertain in the remaining 8 children.33 Generally, operative reduction is

required as ileoileal intussusception is usually not amenable to reduction via contrast enema.

Surgical protocol violations

Beginning in 1969, the NWTS (later incorporated into the COG), evaluated different

treatment strategies conducted through multi-institutional trials. Evidence based, best practice

guidelines designed to improve clinical outcome have arisen from this experience.

Recommendations include the use of proper incisions, sampling of lymph nodes, avoidance of

intraoperative biopsy and avoidance of unnecessary resection of other organs. Proper surgical
 14

management is critical for optimizing outcome. Complications or the need to intensify therapy as

a result of failure to follow evidence based guidelines are considered to have been preventable.

Unfortunately, Ehrlich et al,34 in a review of 3,536 Wilms tumor patients, found a total of 505

cases with at least one surgical protocol violation (564 total were reported) for an overall

incidence of 14.28%. Violations included a lack of lymph node sampling in 365 (64.7%),

avoidable spill in 61 (10.8%), biopsy immediately before nephrectomy in 89 (15.8%), incorrect

abdominal incision in 32 (5.7%) and unnecessary resection of organs in 17 (3.0%), all of which

have been shown to be associated with an increased risk of tumor recurrence.

Lymph node sampling, in particular, is critically important for accurate staging and

should be performed even in the absence of abnormal nodes on preoperative imaging or upon

gross inspection during operative exploration since a review of lymph node sampling by the

NWTS demonstrated a false negative rate of 31% and a false positive rate of 18%, based on

preoperative and intraoperative assessment.35 Lack of regional lymph node sampling prevents

accurate tumor staging and may have consequences for outcome due to understaging. In

addition, failure to sample lymph nodes in younger children (<2 years) with small tumors

(<550gms) will make them ineligible for treatment with surgery only and the avoidance of

adjuvant chemotherapy.

SARCOMA RESECTION

Chest wall tumors

Most malignant chest wall tumors in children are in the Ewing sarcoma family of tumors

although other histologies including rhabdomyosarcoma, osteosarcoma and chondrosarcoma

may be seen. Upfront resection is rarely indicated and reserved for small masses, usually those
 15

less than 3 cm, that can be removed without functional or aesthetic sequelae. For the vast

majority of malignant chest wall tumors, the current management consists of an initial biopsy to

confirm the histologic subtype followed by neoadjuvant chemotherapy and local treatment

(surgery or/and radiation therapy).36 The role of neoadjuvant chemotherapy in this particular

location is to decrease the tumor size, avoid massive chest wall resections and initiate prompt

systemic therapy for occult or overt metastatic disease.37

The most significant long term complication after chest wall resection is scoliosis which

may lead to a restrictive decline in pulmonary function secondary to decrease in lung

compliance, displacement of intrathoracic organs and abnormal movement of ribs and respiratory

muscles.38 Scarring at the surgical site pulls the trunk toward the involved side.39,40 Rib resection

has previously been implicated as a risk factor for the development of scoliosis. A greater curve

is associated with resections above the sixth rib, a higher number of ribs resected, resection of

the posterior segment of the rib and the addition of radiotherapy. Scoliosis is associated with

exercise intolerance due to restrictive pulmonary function.41 If prosthetic material has been left to

cover a chest wall defect, long term complications related to this including erosion and/or

infection of the prosthesis can occur.42

Radiotherapy may be necessary for margins that are microscopically involved after

surgery and large size tumors not amenable to surgical resection. However, the addition of

radiotherapy has been associated with significant morbidity for children with chest wall tumors

including scoliosis, hemivertebrae growth retardation, direct lung damage, cardiotoxicity and

secondary malignancies (sarcomas, acute myeloblastic and lymphoblastic leukemias and

bronchioloalveolar carcinoma, among others).43,44

 16

Extremity musculoskeletal tumors

The decision whether to perform an upfront resection of a localized extremity mass likely

to be a soft tissue sarcoma is based on the size of the lesion and the involvement of critical

structures. In general, lesions less than 5cm in greatest diameter are subjected to an upfront

resection if this can be done with minimal morbidity. Lesions larger than 5cm generally undergo

a biopsy first, either a percutaneous core needle biopsy or an open incisional biopsy.45 Potential

complications of biopsy include bleeding, tumor seeding and wound issues such as tumor

extruding out the incision site. Therefore, biopsy with careful hemostasis should be planned in

such a way that the biopsy tract and scar can be safely included in the definitive surgical

resection. A transverse incisional biopsy will require a more extensive resection at the definitive

surgery compared to a longitudinal incision, which may make coverage difficult and so should

be avoided (Fig. 1). This may lead to local wound complications and resultant delays in initiating

adjuvant chemotherapy and radiation therapy. In cases of bulky soft tissue sarcomas, open

biopsies may be complicated by poor wound healing and fungating lesions; therefore, core

biopsies are recommended in these circumstances.

Nonrhabdomyosarcoma soft tissue sarcomas, unlike rhabdomyosarcoma, are generally

insensitive to adjuvant chemotherapy and wide local excision is still the critical component of

their management.46 For the definitive resection, careful identification of the local neurovascular

bundle and other vital anatomic structures is critical to avoid complications. For these

chemoresistant tumors, consideration should be given for vascular and/or nerve grafting, if

necessary, to remove a large tumor with negative margins. In some anatomic locations, a nerve

may be intimately associated with the tumor and thus sacrifice of the nerve may be required to

obtain appropriate oncologic margins (Fig. 2). In the upper extremity median, radial and ulnar
 17

nerve injury/sacrifice will cause ape-hand deformity, wrist drop and ulnar claw, respectively. In

the lower extremity, peroneal and tibial nerves injury/sacrifice will cause foot drop.

Complications associated with extremity soft tissue sarcoma surgery may be seen at the

time of the initial biopsy or the definitive resection and are mostly related to local wound issues

with an incidence ranging from 2 to 10%.47 Wound complications following resection of a

localized soft tissue sarcoma have been associated with lower extremity location, large tumor

volume and use of preoperative radiation. For patients receiving preoperative radiation therapy,

the wound complication rate increases to nearly 30%.48 These complications often require plastic

surgery involvement and the treatment may require more advanced reconstructive techniques.

Placement of drains may necessary to avoid fluid collections and this should be adequately

planned to allow future resections in case of local recurrences or positive margins. In those cases

requiring the placement of brachytherapy catheters, a drain is also usually indicated in order to

avoid fluid collections that may interfere with brachytherapy delivery. The resected surgical

specimen should be correctly oriented for pathology review and to avoid misinterpretation.

For bone malignancies, endoprosthetic or biological reconstruction is usually required

after the resection of the primary tumor. Complications may occur early or late. Early

complications include poor wound healing, infection, prosthetic instability, neuropraxia and

vascular spasm or injury. Magnetic resonance angiography (MRA) provides good definition of

the relation between the primary tumor and the neurovascular bundle (Fig. 3). Close monitoring

of arterial pulses is critical in the postoperative care. Weak or nonpalpable pulses may require

modification of the extremity angulation in the immediate postoperative time to improve blood

supply. Rarely, thrombectomy may be required. Late complications include hematogenous

infection, fracture, prosthetic loosening, local recurrence, lack of bone growth and limb length
 18

discrepancy. The most frequent and serious complication that delays postoperative chemotherapy

and radiation is poor wound healing. Infection of prosthesis not cleared with antibiotics may

require the removal of the hardware and placement of a temporary antibiotic spacer before a new

prosthesis is considered. Unresponsive infections may require amputation.

Desmoplastic small round cell tumors

The use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

(HIPEC) for desmoplastic small round cell tumor is increasing and entails surgical resection of

all visible tumors in the abdominal cavity followed by infusion of hyperthermic chemotherapy,

most commonly cisplatin.49,50 Whole abdominal radiation therapy is also often part of the

adjuvant therapy for these patients. The combination of systemic chemotherapy, cytoreductive

surgery with HIPEC and whole abdominal radiation therapy has led to improved survival

outcomes compared to historic controls.51 Complications of this procedure in adult patients

include wound infections and enterocutaneous fistulae. Hayes-Jordan et al. evaluated toxicity in

23 children and young adults undergoing 27 HIPEC procedures using cisplatin and they found

renal failure in 5 patients, subclinical decrease in hearing in 1, hematologic toxicity in 2, hepatic

toxicity in 2, cardiotoxicity in 1 and ileus in 1.52

LUNG RESECTION

Primary lung tumors in children are rare; most malignant pediatric lung lesions are

metastases.53 Up to 30% of pediatric cancer patients will have metastases at diagnosis, with the

lung being the most common distant site. The treatment approach for pulmonary metastatic

disease is histology dependent. Some tumors, such as osteosarcoma, require complete surgical

resection of pulmonary metastatic disease for cure, whereas others such as Ewing sarcoma can
 19

be treated with chemotherapy and radiation.54,55 Therefore, the role of the surgeon may vary from

a single nodule biopsy to aggressive pulmonary metastasectomies. For diagnostic purposes,

video-assisted thoracic surgery (VATS) has gained widespread acceptance as a method of

resecting lung nodules although identification of deeper lesions may be difficult. A few

localization techniques have been described such as CT-guided hookwire localization with or

without injection of methylene blue, radioisotope marking under CT guidance and VATS

ultrasound. In our institution, we favor the CT-guided hookwire localization.56 Complications of

this procedure include dislodgement of the hookwire from the lesion, pneumothorax after

localization in the interventional radiology suite, pleuritic pain, lung hemorrhage, hemothorax,

prolonged air leak, pneumonia, retained wire fragment and need for thoracotomy.56

Complications encountered during VATS procedures for lung nodule resection may include

pneumothorax, bleeding, subcutaneous emphysema, port site recurrence, port site infection and

tumor spillage.57 Conversion to open thoracotomy may be required due to nonvisualization of the

lesion, visualization of more lesions than predicted by CT, anatomic constraints such as apical

metastasis or wide implantation and pleural adhesions.58 Postoperative complications associated

with open thoracotomy include pneumothorax, hemothorax, rib fracture, subcutaneous

emphysema and wound problems. In the long term, shoulder elevation, winged scapula and chest

wall asymmetry may be seen in these patients.58 Open thoracotomy can also result in substantial

pleural and pulmonary scarring which can complicate subsequent thoracotomies that are often

needed in these patients. Denbo et al evaluated the long term effect of metastasectomy on

pulmonary function of patients treated for osteosarcoma during childhood and concluded that

abnormal pulmonary function tests were common in these patients but the reduction in lung
 20

volumes and diffusion capacity was relatively mild. Multiple thoracotomies predicted greater

impairment of pulmonary function.59

LYMPH NODE BIOPSY

Surgeons are often asked to perform a lymph node biopsy in children for accurate

diagnosis and staging of both solid tumors and hematopoietic malignancies, lymphoma in

particular. In general, bleeding, infection, lymphocele and lymphedema may occur after a lymph

node biopsy. Complications are intimately associated with the anatomic lymphatic area where

the biopsy is obtained. In the head and neck region, the damage of vascular structures (carotid

artery and jugular vein) may cause life threatening bleeding and postoperative airway

compression from hematoma formation. Damage to nerve structures may cause neurological

defects of the face and shoulder that can be temporary or permanent. Biopsy of lymph nodes

located in the mandibular angle are may cause injury to facial nerve branches. Spinal accessory

nerve injury is estimated to occur after 3% to 8% of posterior triangle lymph node biopsies and it

results in loss of innervation of the trapezius muscle and, consequently, a syndrome of

progressive shoulder disability and chronic pain.60,61 Biopsy of large size lymphatic lesions in the

mediastinum is a challenging procedure for both the surgeon and the anesthesiologist.

Respiratory compromise and vascular collapse on induction of general anesthesia is a well

recognized complication secondary to a decrease in the functional residual capacity, decrease

lung capacity, an increase in lung retractile force and muscle paralysis.62 Newborns and small

children have a small compressible airway, which is associated with significant increased airway

resistance with even a modest degree of narrowing. In addition, the mediastinum is not fixed at

this age and large masses can easily displace the mediastinal structures with compression of the

tracheobronchial tree, superior vena cava or right ventricular outflow tract. Cardiac output may
 21

also be diminished due to pressure on the great vessels. The above alterations are extenuated

with the addition of paralysis. Narrowing of the trachea will also become smaller when the

patient changes from spontaneous to positive pressure ventilation. A thorough preoperative

evaluation should be performed. Prebiopsy therapy including radiation, corticosteroids or

chemotherapy may be required.63 Incisional needle biopsies can be performed under local

anesthesia and mild sedation. Biopsy of bulky lymphatic masses in the abdomen carries the risk

of hemoperitoneum and bowel perforation due to impaired identification of anatomic structures.

The surgical plan and scar orientation for a lymph node biopsy should be meticulous, keeping in

mind the potential need for a future complete lymph node dissection for certain histologies like

melanoma and soft tissue sarcomas.

Complications after lymph node dissection are well recognized and better characterized

in adult patients with breast cancer who undergo axillary lymph node dissection. They include

wound infections, lymphocele, lymphedema of the extremity, limitation of movement,

lymphangitis and numbness.64 Surgical drains are usually required after a lymph node dissection.

Careful care of these drains with daily output recording is mandatory to avoid infections and an

inadequate early removal of the drain.

Retroperitoneal lymph node dissection (RPLND) may be required for patients older than

10 years who present with paratesticular rhabdomyosarcoma.65 Several complications may occur

after this procedure. Lymphocele is the most common complication from RPLND with a highly

variable clinical presentation; patients may be asymptomatic, or present with pain, fever, genital

or lower extremity edema and urinary symptoms.66 Injuries to the ureter, obturator nerve and

pelvic vessels may occur but are relatively uncommon. Retrograde ejaculation is a potential
 22

complication associated with RPLND secondary to damage to nerves responsible for the control

of ejaculation.67

CENTRAL VENOUS CATHETER PLACEMENT

Central venous catheters (CVC) are extremely important in the management of pediatric

cancer patients, providing easy and durable access for the administration of chemotherapy,

antibiotics, blood products and parenteral nutrition. The incidence of CVC complications in this

specific population has been reported to be as high as 40%.68-70 Risk factors associated with CVC

placement include multiple attempts, failed attempts, body habitus and prior catheterizations.71

Complications can occur during CVC insertion or postoperatively. Intraoperative complications

include pneumothorax, hemothorax, arterial puncture, cardiac perforation, arteriovenous fistulas,

nerve injuries (mostly brachial plexus injuries), cardiac tamponade, life threatening arrhythmias,

thoracic duct injuries and death. Postoperative complications include central line-associated

bloodstream infection (CLABSI), catheter malfunction and thrombosis and stenosis or

thrombosis of the catheterized vein. In a recent prospective clinical trial, subclavian vein

catheterization was associated with a lower risk of CLABSI and symptomatic thrombosis of the

vein and a higher risk of pneumothorax than jugular vein or femoral vein catheterization.72 In

considering the relative incidence of CLABSI by site placement, femoral catheters have been

associated with increased CLABSI rates; therefore, femoral catheterization for long term access

should be avoided. Although catheter removal for complete resolution of CLABSI in pediatric

cancer patients has been reported to be necessary in 29-67% of the cases, most CLABSI can be

treated with antimicrobial therapy while the CVC remains in place.73,74 Catheter malfunction due

to thrombosis can usually be solved by the use of urokinase.

 23

General recommendations for avoiding CVC complications include the placement by

well-trained providers, CVC care provided by trained nurses, routine flushing with saline, tissue

plasminogen activator (t-PA) to restore patency to occluded catheters, CVC removal when the

catheter is no longer needed or in case of CVC thrombosis that worsens despite anticoagulation

therapy and ultrasound-Doppler to evaluate vein patency in patients with history of previous

CVC placement. Ultrasound guidance technique is gaining popularity for central vein

catheterization because it can both increase the success rate and decrease the complications

encountered during CVC placement. 75

Another way to decrease the incidence of complications may be to use the technique of

guidewire catheter exchange (GCE). GCE does not appear to increase CLABSI rate and may

indeed maintain a low risk of CLABSI while decreasing potential complications associated with

de novo insertion. The incidence of CVC complications along with the difficulty in venous

access in chronic pediatric cancer patients make the GCE a very useful technique to replace an

existing CVC.76

Retained intravascular fragments after removal of indwelling CVCs are another rare

complication for this group of devices (Fig. 4).77 Patients whose line has been in place for a

longer time are more prone to experience fragment retention.

 24

TABLE 1. Objective Surgical Risk Factors for primary resection of localized neuroblastoma

1) Neck:
1. Tumor encasing major vessel(s) (e.g. carotid artery, vertebral artery, internal jugular
vein)
2. Tumor extending to base of skull
3. Tumor compressing the trachea
4. Tumor encasing the brachial plexus

2) Thorax:
1. Tumor encasing major vessel(s) (eg.subclavian vessels, aorta, superior vena cava)
2. Tumor compressing the trachea or principal bronchi
3. Lower mediastinal tumor, infiltrating the costo-vertebral junction between T9 and T12 (may
involve the artery of Adamkiewicz supllying the lower spinal cord)

3) Abdomen:
1. Tumor infiltrating the porta hepatis and/or the hepatoduodenal ligament
2. Tumor encasing the origin of the celiac axis, and/or the superior mesenteric artery
3. Tumor invading one or both renal pedicles
4. Tumor encasing the aorta and/or vena cava
5. Tumor encasing the iliac vessels
6. Pelvic tumor crossing the sciatic notch

4) Dumbbell tumors with symptoms of spinal cord compression: Any location

5) Infiltration of adjacent organs/structures: Diaphragm, kidney, liver, duodeno-pancreatic block, and

mesentery

(Adapted from Cecchetto G, Mosseri V, DeBernardi B. et al. Surgical risk factors in primary surgery for
localized neuroblastoma: the LNESG1 study of the European International Society of Pediatric Oncology
Neuroblastoma Group. J Clin Oncol 2005: 23:8483-9)
 25

FIGURES

Figure 1. Oblique and anterior biopsy site at the thigh (A) that obligates to a wider
muscle

resection to include the biopsy tract (B,C). Orientation of final scar (D).
 26

Figure 2. Peroneal nerve intimately associated with proximal fibula osteosarcoma and
thus the

nerve was sacrificed to obtain appropriate oncologic margins

 27

Figure 3. Magnetic resonance angiography showing the relation between a left proximal
fibula

osteosarcoma and the popliteal neurovascular bundle

 28

Figure 4. Retained intravascular catheter in the innominate vein after removal of

subcutaneous

port
 29

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