Surgical Approaches to Childhood Cancer

Contents

11.1 Principles of Treatment . . . 219

11.2 Description of Treatment . . . 219

11.3 Method of Delivery . . . 220

11.3.1 Preoperative Evaluation . . . 220

11.3.2 Postoperative Nursing Care . . . 221

11.4 Potential Side Effects . . . 222

11.4.1 Complications of Medical Therapy Requiring Surgical Evaluation . . . 222

11.4.2 Complications Arising from Surgical Management of Solid Tumors . . . 223

11.5 Special Considerations . . . 223

11.5.1 Vascular Access Devices . . . 223

11.6 Future Perspectives . . . 224

11.6.1 New Surgical Techniques and Directions for Future Research . . . . 224

References . . . 225

Bibliography . . . 225

11.1 Principles of Treatment

A multimodal treatment approach has improved sur- vival rates of children with cancer. This multifaceted approach may include surgery, chemotherapy, radia- tion, or a combination of these. Many advances in the treatment of childhood cancers have been through development of intensive chemotherapy and radio- therapy regimens. Due to this multimodal approach to pediatric malignancies, there has been a decreased need for radical surgical procedures. However, the surgical team is still required to be an integral part of many aspects of pediatric oncology care, particularly supportive care and related complications. Common surgical techniques in the management of childhood malignancies include, but are not limited to, those listed in Table 11.1.

11.2 Description of Treatment

A local and regional determination of the extent of disease, or staging, is performed at diagnosis and re- lapse (Leonard, 2002). A system of staging exists for many pediatric tumors and helps to determine both prognosis and treatment, relating the extent of dis- ease at diagnosis to the subsequent clinical course. It is based on the premise that cancer of similar histo- logic features and sites of origin grows and metasta- sizes in a similar manner. All treatment protocols are based on stage of the tumor, which determines such factors as use of radiotherapy and intensity of chemotherapy. Correct staging allows the medical team to minimize therapy and yet maximize cure.

This further provides the opportunity to limit thera-

Surgical Approaches to Childhood Cancer

Jill Brace O’Neill

py to minimize the long-term sequelae of different treatments.

Similar to staging of the disease, use of the correct biopsy technique is critical to the childhood cancer patient. The diagnosis of childhood cancer requires a multimodal tumor analysis carefully planned before the biopsy by the pediatric oncologist, pathologist, and surgeon. Biopsy is best performed in a pediatric cancer center because optimal use of the surgical specimen can be performed only in specialized childhood cancer centers. Considerations when se- lecting the method and type of incision include the creation of an incision that may be incorporated in the future incision used for resection, the need to avoid contaminating an uninvolved body cavity, the need to avoid contaminating otherwise uninvolved lymphatic drainage, and adequate staging at the time of biopsy if the child is to receive preoperative chemotherapy.

Because pediatric cancers include a diverse group of malignancies, there is no single surgical procedure that can be used in all cases. Regardless, the goal of treatment is cure that will best be achieved with mul- timodal treatment (i.e., chemotherapy, radiation therapy, surgery, or a combination of these).

11.3 Method of Delivery 11.3.1 Preoperative Evaluation

The pediatric oncology patient undergoing surgery warrants detailed consideration with regard to peri- operative and anesthetic management. Clinically, this includes coagulation and transfusion evaluation and support, evaluation of tumors that result in an anteri- or mass, and immunization of those patients under- going splenectomy. For patients already treated with chemotherapy, assessment of cardiac, pulmonary, re- nal, and electrolyte status is also critical (Shamberg- er et al., 2002). Close coordination between services will avoid duplication of studies and decrease the need for repeated sedation for procedures or diag- nostic tests.

A complete blood count, including hemoglobin, white blood cell count, platelet count, and coagula- tion studies, is necessary prior to surgery. Low blood counts can be corrected using granulocyte colony stimulating factor and red blood cell and/or platelet transfusions when indicated. It is difficult to discern, however, particularly in the leukemic patient, whether neutropenia may be functional or a result of

Table 11.1. Common surgical techniques for management of childhood malignancies

Procedure Description

Biopsies, including fine needle aspiration, Biopsies include taking a sample of the desired tissue by means of a core biopsy, and incisional/open Biopsies include taking a sample of the desired tissue by means of a or excisional biopsy needle aspiration, a core biopsy for larger specimens, and open

procedures to remove entire sections of tumor and/or lymph nodes.

Staging and second-look surgery Staging is used when treatment depends on the location of the cancer and the extent of disease involvement.“Second-look” procedures are used to assess response to nonsurgical treatment.

Debulking Debulking involves removing a portion of the tumor mass when it is not possible to remove the entire mass. This may be done as first-line therapy or after receiving chemotherapy or radiation.

Management of metastasis Provides pathologic confirmation of metastasis via biopsy and can include staging and/or debulking efforts.

Supportive care surgery Surgeries necessary for placement of central venous access devices/catheters or feeding tubes vital to supportive care measures.

Palliative surgery Palliative surgery is done to relieve the symptoms caused by tumors

that have been unresponsive to medical therapy. It may also be done

to relieve pain and bleeding.

a bone marrow “packed” with leukemic cells. The clinical situation will mandate the need for transfu- sion support of the oncologic surgical patient. Im- munodeficient patients should receive irradiated and leukocyte-reduced blood products. Patients who are serologically cytomegalovirus (CMV)-negative should receive CMV-negative blood products as well.

Most often, elevations in prothrombin time (PT) and partial thromboplastin time (PTT) are acquired defects. For the patient with a normal platelet count and fibrinogen, an injection of vitamin K – or for im- mediate correction, fresh frozen plasma – can correct these abnormalities. For the patient with other asso- ciated abnormal laboratory values (e.g., fibrinogen), disseminated intravascular coagulation (DIC) or liv- er disease should be considered (Table 11.2).

A child with a mediastinal mass is at risk for respi- ratory collapse due to airway compression during in- duction of general anesthesia. Anterior mediastinal masses may also compress the superior vena cava, causing some or all manifestations of superior vena cava syndrome. These symptoms include orthopnea, headache, dizziness, fainting, plethoric facial swelling, jugular venous distension, papilledema, and pulsus paradoxus. Computed tomography (CT) is helpful in diagnosing the mediastinal mass and the degree of tracheobronchial compression (Shamberger, 1999).

Pulmonary function testing can also be important in evaluating this type of patient. Those patients with a mediastinal mass that will not shrink with chemo- therapy, emergency radiation therapy, or steroids may have conscious sedation considered for obtain- ing diagnostic biopsy material.

A child needs to be immunized at least two weeks before undergoing a splenectomy. The spleen con- tains macrophages, which provide defense against infections. Necessary vaccines include Haemophilus influenzae type B (Hib), pneumococcal vaccine, and meningococcal vaccine.

Patients who have a history of receiving bleomycin, anthracycline agents, or radiation therapy will be as- sessed differently prior to surgery than those chil- dren who have not been exposed to these treatments.

Pulmonary fibrosis with a loss of lung volume, com- pliance, and diffusing capacity can occur as a result of bleomycin, BCNU, or radiation therapy to the lung;

therefore, these patients need to be identified to the anesthesiologist as high-risk. All patients who have a history of receiving anthracycline agents (cardiotox- ic) or mediastinal radiation will also need further preoperative evaluation, which can include an echocardiogram (ECHO) and/or multigated angiog- raphy (MUGA).

Preparation of the patient and his or her family cannot be overemphasized as a vital part of preoper- ative nursing management. Besides ensuring ade- quate nutrition, confirming no evidence of infection, and checking that laboratory criteria are met or with- in normal limits, the child and family will need edu- cation to support them. Play therapy is often used to help prepare children for surgery. This may include allowing the child to handle medical equipment, pro- viding developmentally appropriate explanations, and giving a tour of the operating room if time per- mits; these measures can positively influence the op- erative experience. Assessing the patient and family’s learning needs is an important part of this prepara- tion phase before surgery.

11.3.2 Postoperative Nursing Care

The child with cancer is often a high-risk surgical pa- tient. Postoperative care of these patients must in- clude attention to the following areas: prevention of infection, airway maintenance and oxygenation, fluid and electrolyte balance, pain control, nutritional sup- port, and wound care.

Table 11.2. “Ideal” blood counts prior to surgical procedure

Platelets >50,000/mm

Hemoglobin >6–8 g/dl

Absolute neutrophils >1,000/mm

Normal coagulation studies (including thrombin time,

fibrin degradation products, fibrin monomers,

and D-dimer levels)

11.4 Potential Side Effects

Immunosuppression related to cancer therapy pres- ents the increased potential for complications due to infectious causes. A secondary problem related to this is that signs and symptoms of infection are often delayed in these patients because of their immune suppression. Therefore, surgical oncology patients require close monitoring postoperatively.

11.4.1 Complications of Medical Therapy Requiring Surgical Evaluation

Bowel obstruction can be partial or complete and may be caused by tumors, adhesions, constipation, ileus as a result of vincristine, or graft-vs.-host dis- ease in hematopoietic stem cell transplant patients.

Perforation and necrosis are rare but can occur.

Treatment usually includes hydration, antibiotics, and laxatives for first-line therapy.A nasogastric tube is inserted to relieve pressure, and subsequent sur- gery is used if the obstruction persists despite the previous interventions.

Pancreatitis is an inflammation of the pancreas.

Symptoms are nausea, vomiting, and right-sided ten- derness, and the diagnosis is confirmed by physical examination and elevated lipase and amylase. CT or ultrasound shows an enlarged and inflamed pan- creas. The cause is tumor lysis and/or chemotherapy (asparaginase or, less frequently, steroids). Treatment includes stopping the causative agent and restricting the diet. Necrotizing pancreatitis may require surgi- cal debridement in extreme cases. Maintenance of nothing-by-mouth status with total parenteral nutri- tion until symptoms resolve is the usual first-line therapy, with a subsequent low-fat diet prescribed.

In neutropenic children, inflammation of the ce- cum (typhlitis) can occur postoperatively and can progress rapidly to gangrene or perforation of the bowel. Symptoms include abdominal pain in the right lower quadrant, fever, distention, diarrhea, and vomiting (see chapter 15). An x-ray film can demon- strate bowel wall thickening, and a CT scan confirms inflammation and its extent. Treatment includes an- tibiotics and bowel rest. Laparotomy is a surgical

intervention to remove the diseased bowel if there is clinical deterioration, persistent gastrointestinal bleeding, uncontrolled sepsis, or evidence of perfora- tion.

Different types of infections can occur and are not uncommon in the immunosuppressed pediatric on- cology patient. Surgical site infections are the leading type of infection among hospitalized patients. Infec- tions of the surgical wound/site or the central line site often can be treated with antibiotics without having to remove the newly-planted central venous access device. Symptoms of wound infection are tenderness, erythema, fever, and wound drainage. Wound infec- tions usually occur after 5–7 days postoperatively.

Other than antibiotics, wound infection treatment may also include excision and drainage, particularly when symptoms of cellulitis are present. The surgeon may debride a wound when infection interferes with healing. Temporary drains are used to remove fluid accumulation.

Currently clinical practice standards for the pre- vention of surgical site infections have been derived from guidelines prepared by the American College of Surgeons and the Centers for Disease Control (CDC) (Nichols, 2000). These guidelines include educational preparation of the patient/family; antisepsis of the surgical team; management of infected surgical per- sonnel; antimicrobial prophylaxis; intraoperative ventilation; intraoperative cleaning and disinfection;

microbiologic sampling; sterilization of surgical in- struments, surgical attire, and drapes; and asepsis and sterile technique, incision care, and surveillance.

Incision care is defined per the aforementioned guidelines as following recommendations during the postoperative phase to prevent surgical site infec- tions. Specifically, these recommendations include the following:

▬ Protect incision with sterile dressing 24–48 hours postoperatively

▬ Wash hands before and after any contact with the surgical site

▬ Use sterile technique when changing dressing

▬ Educate patient and family regarding proper inci-

sion care, symptoms of an infection, and the need

to report these symptoms.

Pneumothorax is the collapse of a lung and can be spontaneous, a presenting symptom of metastatic lung disease, or a direct result of an invasive proce- dure (e.g., thoracotomy). The most common symp- toms of pneumothorax are shortness of breath and chest pain. A chest x-ray revealing lung collapse will confirm the diagnosis. Symptoms can develop within 24 hours postoperatively. The treatment includes lung expansion via insertion of a chest tube. The tube is left in place until the x-rays and the clinical condi- tion of the patient show that the lung has re-expand- ed.

11.4.2 Complications Arising

from Surgical Management of Solid Tumors Operations for solid tumors can present risks unique to the type of tumor being approached. Specific tu- mor considerations include, but are not limited to, neuroblastoma and Wilms’ tumor. Surgery is a cor- nerstone of treatment in neuroblastoma. Neoadju- vant chemotherapy has made surgical resection of locally advanced tumors more feasible and has im- proved local control and survival (Rubie et al., 2001).

With advanced tumors, injury to major vessels occurs and the need for extended resections becomes neces- sary. The most common intraoperative complication is the need for nephrectomy. In addition, extensive dissection of renal vessels can lead to ultimate dam- age that may not become apparent until the postop- erative period. Renal impairment is evidenced by anuria/oliguria.

In children with Wilms’ tumor, surgical complica- tions are potential causes of significant morbidity.

However, with the introduction of preoperative chemotherapy and standardization of surgical tech- niques, the rate of surgical complications has been markedly reduced. Risk factors for the development of surgical complications in patients with Wilms’ tu- mor include advanced local tumor at time of diagno- sis, intravascular tumor extension, and resection of other organs at the time of nephrectomy. The most common complication is intestinal obstruction, fol- lowed by hemorrhage, wound infection, and vascular injury. Furthermore, two risk factors related to local recurrence of Wilms’ tumor are directly related to the

type of surgical resection performed: The presence of microscopic tumor at the margin of the surgical re- section and intraoperative tumor spill are both fac- tors that can predict disease recurrence. Other child- hood cancers that are benefiting from advances in surgical techniques and coordination with multi- modality treatment regimens include rhabdomyo- sarcoma, Ewing’s sarcoma, germ cell tumors, and he- patoblastoma.

11.5 Special Considerations 11.5.1 Vascular Access Devices

Vascular access devices (VADs) are vital in managing and treating childhood cancer. Central venous catheters provide for the long-term delivery of pro- longed courses of chemotherapy as well as parenter- al nutrition, blood products, intravenous fluids, an- tibiotics, pain medications, and other agents. Fur- thermore, they are useful devices for repeated blood sampling. There are three types of devices most com- monly used in the pediatric cancer population: pe- ripherally inserted central venous catheters (PICCs), tunneled external central venous catheters (CVCs), and the implanted vascular access device or port-a- catheter. The CVC uses a flexible silicone tube placed in a central vein that exits thorough a subcutaneous tunnel. The CVC has historically been placed surgi- cally, but more recently is also being inserted by the interventional radiology service with the use of ul- trasound image guidance. Totally implanted devices or ports consist of a reservoir implanted in a subcu- taneous pocket connected to a silicone catheter placed in a central vein.

Despite the fact that the central VAD has greatly improved the quality of care received by pediatric on- cology patients, these devices are not without the po- tential for complications, including pneumothorax, hemothorax, arterial perforation, air embolism, nerve injury, catheter malposition, infection, and oc- clusion or thrombosis.

The most common complications of these devices

are infection and occlusion. The incidence of in-

travascular catheter infection varies considerably by

type of catheter, frequency of catheter manipulation,

and patient-related factors (e.g., underlying disease and acuity of illness). The majority of serious catheter-related infections are associated with cen- tral venous catheters (O’Grady et al., 2002). Migration of skin organisms at the insertion site into the cuta- neous catheter tract with colonization of the catheter tip is the most common route of infection for periph- erally inserted catheters. The majority of catheter-re- lated bloodstream infections in children are caused by coagulase-negative staphylococci. Exposure to lipids has also been identified as an independent risk factor in certain pediatric populations. Because of the limited vascular sites in children, attention should be given to the frequency with which catheters are re- placed in these patients. One study found no rela- tionship between duration of catheterization and the daily probability of infection, suggesting that routine replacement of VADs does not reduce the incidence of catheter-related infection (O’Grady et al., 2002).

Indicators that reduce the incidence of catheter-relat- ed bloodstream infections are

1. Implementation of educational programs that in- clude didactic and interactive components for those who insert and maintain catheters

2. Use of maximal sterile barrier precautions during catheter placement

3. Use of chlorhexidine for skin antisepsis

4. Removal of the catheter when it is no longer re- quired for treatment (O’Grady et al., 2002).

Catheter occlusions can be intermittent, sluggish, partial, or complete/total and can result from several different mechanisms. Patency may be affected by anatomical obstruction due to compression of the catheter between the first rib and clavicle or by im- proper catheter tip placement. Occlusion may also re- sult from precipitation caused by the administration of incompatible drugs or infusates; however, this is a less common cause.

The most common cause of catheter occlusion is thrombus formation within the lumen of the catheter, in the portal reservoir, or at the catheter tip.

Venous stasis, hypercoagulability, and local trauma of the intima of the vein wall are contributing factors to the development of catheter thrombosis. The majori- ty of thrombi causing central catheter occlusion de-

velop without symptoms. Warning signs of catheter malfunction are most often recognized by an experi- enced clinician. One study found that persistent asymptomatic vascular occlusion was a late compli- cation of CVC placement for treatment of childhood malignancies, although the frequency was low among patients treated primarily for solid tumors (Wilimas et al., 1998).

Catheter occlusions due to the formation of a thrombus are treated by instilling a thrombolytic agent. Currently, recombinant tissue plasminogen ac- tivator (rt-PA) or alteplase is used to restore patency to occluded catheters. Rt-PA is a fibrin-specific thrombolytic agent produced through recombinant DNA technology. The optimal rt-PA dose, solution volume, and dwell time for the clearance of throm- bosed CVCs is 2 mg (1 mg/ml), with a 30-minute to 2-hour dwell time. For the persistent occlusion, this dose may be repeated once. Clinical experience has demonstrated that increasing the dwell time (e.g., al- lowing the rt-PA to remain in the catheter overnight) has also had success for persistent occlusions.

Two common complications associated with the use of VADs, infection and occlusion, can be dimin- ished by adhering to institutional protocols for catheter insertion, catheter site dressings, and drug and fluid administration. However, compliance with catheter care regimens also needs to occur in the home care setting. Standardization of line care be- tween the treating institution and the home care agency is key to reducing confusion and anxiety in the child and family. Teaching is based on the educa- tional level of the child and parents as well as on their preferred methods of learning.

11.6 Future Perspectives 11.6.1 New Surgical Techniques and Directions for Future Research

The past decade has brought significant changes to the surgical management of the child with cancer.

Currently, pediatric surgical oncology has become

extremely complex, requiring advanced technical

skills using newly developed equipment. Minimally

invasive surgery (MIS) is an example of one of the

most recent additions to the surgical armamentari- um. MIS is used for a variety of abdominal and tho- racic procedures and describes a surgical procedure accomplished with instruments directed through cannulas. The advantages of MIS for certain types of operations include smaller wound size, less tissue ex- posure, and minimal tissue and organ manipulation.

Because the body’s response to MIS is different from its response to open surgical procedures, there is less stress imposed on the body, postoperative pain is de- creased, and respiratory management and activity re- strictions are also decreased. Examples of MIS in- clude, but are not limited to, fundoplication, colon pull-through for Hirschsprung’s disease, splenecto- my, and thoracoscopic procedures.

The surgical oncology team now includes not only physicians and nurses but also scientists, computer specialists, and bioengineers. This is critical as new surgical procedures and devices are directed by com- puter technology, including robotics, telepresence, and virtual reality. Several types of surgical robotic systems have been developed that allow the perform- ance of surgery with a higher degree of accuracy than that capable by human hands (Bagnall et al., 2002).

Telepresence is the ability to perform a task or proce- dure using a remote manipulator and video image.

This remote-controlled system was developed to solve deficiencies of MIS such as the absence of three- dimensional imaging, poor dexterity, and loss of sen- sory feedback. Lastly, virtual reality permits surgical intervention on imaginary patients. For pediatric surgical oncology, the implications of this new tech- nology are immense. Tumors that were once deemed inoperable can now be excised with the use of robot- ics. Similarly, surgeons who are specialists in a par- ticular tumor type will be able to perform surgical procedures from afar.

Today the surgeon administers vital services in the care of children and adolescents with malignant dis- ease. Managing vascular access and its complications, as well as providing supportive care and appropriate intervention for medical complications of chemo- therapy, have become the standards for the modern pediatric surgical oncologist.

References

Bagnall-Reeb H., Perry, S. (2002) Surgery. In Rasco Baggott, C., Patterson Kelly, K., Fochtman, D., Foley, G.V. (eds) In Nurs- ing Care of Children and Adolescents with Cancer (3rd edn, pp. 91–115). Philadelphia: Saunders

Leonard, M. (2002) Diagnostic evaluations and staging proce- dures. In Rasco Baggott, C., Patterson Kelly, K., Fochtman, D., Foley, G.V. (eds) In Nursing Care of Children and Ado- lescents with Cancer (3rd edn, pp. 66–89) Philadelphia:

Saunders

Nichols, R. (2000) Guidelines for prevention of surgical site in- fection. Bulletin of American College of Surgeons 85:23–29 O’Grady, N.P.,Alexander, M., Patchen Dellinger, E., Gerberding, J.L., Heard, S.O., Maki, D.G., Masur, H., McCormick, R.D., Mermel, L.A., Pearson, M.L., Raad, I.I., Randolph, A., Wein- stein, R.A. (2002) Guidelines for the prevention of intravas- cular catheter-related infections. Pediatrics 110:1–24 Rubie, H., Plantaz, D., Coze, C., et al. (2001) Localized and unre-

sectable neuroblastoma in infants: Excellent outcome with primary chemotherapy. Medical Pediatric Oncology 36:247–250

Shamberger, R.C., Jaksic, T., Ziegler, M.M. (2002). General Prin- ciples of Surgery. In Pizzo P.A., Poplack D.G. (eds) In Prin- ciples and Practice of Pediatric Oncology (4th edn., pp.

351–367). Philadelphia: Lippincott Williams & Wilkins Shamberger, R.C. (1999) Preanesthetic evaluation of children

with anterior mediastinal mass. Seminars in Pediatric Surgery 8:61–68.

Wilimas, J.A., Hudson, M., Rao, B., Luo, X., Lott, L. Kaste, S.C.

(1998) Late vascular occlusion of central lines in pediatric malignancies. Pediatrics 101:E7

Bibliography

Andrassy, R.J. (2002) Advances in the surgical management of sarcomas in children. The American Journal of Surgery 184:484–491

Miller, S.D., Andrassy, R.J. (2003) Complications in pediatric

surgical oncology. Journal of the American College of Sur-

geons 19:832–837