Cancer in Children: Clinical Management, 5th Edition

Chapter 7. Surgery in paediatric oncology

Helene Martelli

Introduction

The increased survival and decreased morbidity for children with cancer has been one of the most gratifying success stories during the last 30 years. This progress is related to several factors, including the sensitivity of childhood malignant tumours to chemotherapy and the use of a multidisciplinary approach to management. Because of increasingly effective chemotherapy, the role of surgery in the management of childhood cancer has changed considerably from being the only modality available to treat many solid tumours to being one of several therapies which are needed to achieve success. Nowadays, the paediatric surgeon interacts with a multidisciplinary team of experts including paediatric oncologists, radiologists, pathologists, and radiotherapists. The best outcome will always be achieved by close cooperation between specialists, each clearly understanding the efficacy and limitations of various forms of treatment. Therefore the paediatric surgeon should be engaged in the child's management from diagnosis onwards and be aware of all the diagnostic and therapeutic modalities available. Frequently, the paediatric surgeon is the first physician who may suspect a malignant tumour in a child presenting with a palpable mass. Except in emergencies, a thorough consideration of the possible differential diagnoses should be made before any surgical procedure is undertaken, ideally in discussion with the oncology team.

Even if most paediatric solid tumours also require systemic treatment, adequate local therapy remains a major goal and determines the success of therapy in the great majority of tumours. Adequate local therapy is mainly represented by surgery in children, especially infants, but it may include other forms of treatment such as external beam radiotherapy or brachytherapy. Surgical techniques have progressed in recent decades from radical and potentially mutilating interventions to conservative organ-sparing procedures, mainly because of more effective chemotherapy and the development of combined treatments, such as surgery and brachytherapy, especially in very young children. This has occurred in parallel with a general trend in the treatment of cancer in children of aiming to decrease the intensity of all therapies, with their risk of long-term sequelae, in patients with good prognostic factors, while increasing it in patients with poor prognostic factors. Most malignant tumours are now treated according to multinational clinical trials which include precise guidelines for all the specialists in the oncology team. Theoretically, a paediatric surgeon should not operate on any malignant tumour without being aware of the surgical guidelines in the protocol currently in use for that particular diagnosis.

Surgery may be necessary at different stages during the management of malignant tumours: initially for surgical biopsy or tumour resection (primary excision and re-excision), or after neoadjuvant chemotherapy for secondary resection, or at relapse. Emergency operations are sometimes unavoidable if there is rapid enlargement of the tumour, torsion, or perforation.

The surgeon also has a role in the supportive care of patients, facilitating treatments given by other members of the oncology team or treating complications related to other therapies.

Emergency procedures

Because of the improved accuracy and availability of imaging facilities, the diagnosis of tumour is usually recognized before the first surgical procedure is undertaken. In rare abdominal emergencies, such as intestinal intussusceptions or gonadal torsion, the tumour may not have been diagnosed preoperatively. The surgeon should always try to avoid radical surgery (e.g. right hemicolectomy in a Burkitt lymphoma, cystectomy in a pelvic rhabdomyosarcoma, bilateral oophorectomy, etc.) and only perform a biopsy on such tumours. Sometimes, although a tumour has been diagnosed, the surgeon will need to perform an emergency procedure because of rapid enlargement of the tumour by intratumoral bleeding, or intraabdominal haemorrhage due to spontaneous or traumatic tumour rupture. Even in such cases, it is desirable to follow protocol requirements and avoid radical surgery.

Biopsy

The acquisition of adequate tissue samples is essential not only for diagnosis but also for prognostic biologic information and evaluation of treatment efficacy during follow-up. Communication with the pathologist before taking the specimen is always good practice.

There are several methods of obtaining tissue specimens:

·  fine-needle aspiration cytology

·  needle biopsy for a core of tissue (Tru-cut needle biopsy)

·  surgical biopsy (incisional or excisional) obtained by open or minimally invasive surgery

·  endoscopic biopsy (in specific sites such as bladder or vagina)

·  stereotactic biopsy (for brain tumours).

Directed-needle biopsies using ultrasound or CT guidance give better samples than blind biopsies. They may be performed by clinicians or radiologists.

Fine-needle aspiration cytology is rarely used in the diagnosis of paediatric neoplasms because it usually does not provide sufficient material for the necessary investigation. It may sometimes be relevant to confirm clinically suspected regional node involvement.

Needle core biopsies can provide adequate tissue to allow accurate diagnosis of the majority of paediatric neoplasms. At least three cores should be taken to permit adequate studies, including immunohistochemistry. However, the paucity of material frequently makes it difficult for the pathologist to provide detailed information, for example regarding the presence or absence of anaplasia in nephroblastoma or tumour grading in soft tissue sarcoma.

Open surgical biopsies are often necessary, especially in tumours with obvious heterogeneity on initial imaging, in order to obtain a representative sample. Biopsy may be total (excisional) or partial (incisional). In small suspect soft tissue lesions, it is sometimes possible to perform an excisional biopsy with clear margins. In all other situations, biopsy should be incisional. Biopsy incision should be planned so as to allow the biopsy scar to be excised at the time of definitive resection. This is particularly important in bone and soft tissue lesions arising in the limbs or in the trunk or abdominal walls. Biopsies may also be obtained using minimally invasive surgery, i.e. utilizing laparoscopy, thoracoscopy, or mediastinoscopy. These techniques are very useful and may decrease postoperative pain and the duration of postoperative recovery. Nevertheless, the rules of surgical oncology still apply and it is important to avoid tumour spillage in the abdomen or the pleural cavity.

Staging

There is no single uniform staging approach for childhood malignancies and the surgeon needs to be aware of the requirements for staging each tumour type according to current protocols in use in his or her center. Pretreatment staging procedures are mainly based on imaging (ultrasound, CT scanning and/or MRI, scintigraphy) but also, in specific tumours, on biologic markers (α-fetoprotein and human chorionic gonadotrophin in germ cell tumours), cytogenetics, molecular biology (N-myc oncogene status in neuroblastoma), etc. Surgery alone is no longer considered as a staging procedure, even in Hodgkin disease, although many staging systems include an assessment of the resectablity of the tumour (for instance that used in the National Wilms Tumor Study (NWTS) in North America, and the International Neuroblastoma Staging System). In hepatic tumours treated with SIOPEL protocols, the PRETEXT staging system (PREtreatment EXTent of the disease) identifies not only the extent of the disease but also the type of resection to be performed.1

Primary resection

Primary resection is a surgical procedure performed at diagnosis before any other treatment (chemotherapy or radiotherapy) has been delivered. The aim of primary resection is to achieve complete resection (currently defined as R0: microscopically complete resection) without danger or unnecessary functional compromise. This should be attempted only after careful evaluation of the resectability of the tumour with optimal imaging and discussion with radiologists and oncologists. Extensive ‘mutilating’ operations should never be considered at primary resection. A ‘mutilating’ operation is defined as one leading to significant long-term anatomical, functional, or cosmetic impairment, for example orbital exenteration, major resection of the face, pneumonectomy, pelvic exenteration with permanent intestinal or urinary diversion, total cystectomy, total prostatectomy, hysterectomy, limb amputation, or extensive muscular resection.

The first requirement for considering primary resection is to establish the absence of distant metastases. Some localized and potentially resectable tumours are always treated with preoperative chemotherapy, even if they involve a paired organ. This mainly applies to nephroblastoma in children aged >6 months treated according to the current European protocol (SIOP 2001). The approach is different in North America where patients with localized nephroblastoma may undergo nephrectomy prior to the administration of chemotherapy. In the NWTS, patients are not treated with chemotherapy without histologic confirmation of the maligancy and the surgeon is asked to remove the tumour at diagnosis, define stage by careful evaluation of the liver, the lymph nodes, and the contralateral kidney, and avoid tumour rupture which would mandate postoperative radiotherapy. However, SIOP studies have demonstrated that preoperative chemotherapy can shrink the tumour, downgrade the stage, and reduce the incidence of intraoperative tumour rupture and postoperative complications.2,3

Although primary surgical excision may appear to be indicated in some tumours, it may be preferable to stop the attempt and only perform a biopsy rather than to try to remove a mass for which excision would prove to be more invasive than predicted by imaging. Nevertheless, there are certain situations in which primary resection is appropriate.

Localized ovarian or testicular malignant germ cell tumours are often operated on before chemotherapy, sometimes as an emergency procedure following suspicion of torsion. Even in these cases, protocol guidelines should be followed with orchidectomy and high ligation of the cord in testicular tumours, and with salpingo-oophorectomy in ovarian tumours. If the levels ofα-fetoprotein and human chorionic gonadotrophin are normal preoperatively, and if the tumour looks benign, well encapsulated, and more cystic than solid, the surgeon should remember that benign teratomas are much more frequent than malignant germ cell tumours and that these should be treated conservatively with tumorectomy and organ preservation.4,5

Localized rhabdomyosarcoma (RMS) arising in the paratesticular site, the walls of the trunk, the limbs, or the dome of the bladder may be operated on before chemotherapy if complete resection is feasible without danger or mutilation.

Localized neuroblastoma (abdominal or thoracic) may be operated on before chemotherapy if the surgeon is able to remove the tumour macroscopically without organ impairment and excessive haemorrhage. Factors determining resectability which must be evaluated before surgery are the relationship of the tumour to vessels and neighbouring organs (kidneys, liver, pancreas) and the possibility of intervertebral and intraspinal extension. If the renal pedicle is included in the tumour, the risk of nephrectomy is high and preoperative chemotherapy should be considered.6,7

Some adult-type soft tissue sarcomas, with unproven chemosensitivity, may be best operated on at diagnosis if a conservative procedure seems feasible.

Finally, most brain tumours are operated on at diagnosis, sometimes with complete excision, but most frequently with incomplete excision after a debulking procedure. The concept of debulking surgery was introduced about 30 years ago in the treatment of neuroblastoma. When a tumour was not completely resectable, it was thought best to remove as much of the bulk as possible and to treat the residual tumour with chemotherapy or radiotherapy. Nowadays, debulking surgery is not recommended except in brain tumours, since in most primary unresectable tumours preoperative chemotherapy leads to an easier and less dangerous operation and a greater chance of complete resection with a conservative procedure.

Primary reoperation

The aim of primary reoperation is to achieve complete resection (R0) in patients with microscopic (certain or possible) residue before other therapies are given, if this can be done without danger or mutilation. This particular approach is important in RMS and non-RMS soft tissue sarcoma. If a primary marginal excision or excisional biopsy (not recommended) has already been done, or where histologic evaluation is inadequate, primary re-excision should be considered.8 This applies particularly to trunk, limb, and paratesticular sarcomas. The interval between initial surgical approach and chemotherapy, including primary re-excision, should not exceed 8 weeks.

Secondary operations (after chemotherapy)

Except for some localized tumours (described above) which can benefit from primary surgery, the majority of childhood malignant tumours are operated on after neoadjuvant chemotherapy in order to achieve complete resection (R0) of a residual mass. The intended benefit of preoperative chemotherapy is to reduce the volume and vascularity of the tumour, facilitating complete removal of the tumour with organ preservation, avoiding tumour rupture (except in neuroblastoma where peroperative fragmentation of the tumour has no adverse effect on the outcome), and downstaging the tumour to decrease postoperative treatment.

Secondary operations may be considered either as delayed primary surgery (e.g. in nephroblastoma or hepatoblastoma) or as a second-look procedure for resection of a residual mass after initial chemotherapy (e.g. in RMS or bone tumours). Some tumours, such as osteosarcoma or hepatoblastoma, cannot be cured without complete resection of the local tumour. In other tumours, such as Ewing sarcoma or RMS, adequate local therapy may include a combination of surgery and radiotherapy in order to obtain the best results. In RMS localized in the prostate and/or the bladder neck, the surgical removal of the tumour and the insertion of brachytherapy tubes during the same procedure may be planned with the brachytherapist. This attempt is made to avoid the morbidity of prostatectomy in very young boys.9,10 The timing of secondary operations should be carefully discussed with the oncologist. For instance, in metastatic neuroblastoma or in patients with stage III neuroblastoma, when the tumour is growing around the major abdominal vessels or in the renal pedicle, resection of the tumour may lead to major complications such as chylous ascitis or the need for nephrectomy, and it may be preferable to give further high-dose chemotherapy before surgery, rather than after a long complicated postoperative course or to a child with a single kidney.

Sometimes the patient achieves complete clinical and radiologic remission after initial chemotherapy. In bone tumours, surgical resection (or irradiation if surgery is not feasible) of the bone is necessary even after apparently complete remission. Limbs can be preserved by local excision of the bone tumour and reconstruction with an internal custom-made prosthesis or using bone auto- and allografts. In other tumours, such as RMS, secondary operations for verification of local control do not reliably establish complete histologic remission and are no longer indicated if no tumour is visible clinically, endoscopically, and radiologically.11

Surgery for relapse

The surgical procedure at relapse will depend on the treatment used during primary therapy, but mutilating operations may be justified at this stage, particularly if radiotherapy options have already been exhausted. If the tumour was chemosensitive, it is generally preferable to operate after a trial of second-line chemotherapy.

Surgery for metastasis

Surgery for initial or secondary metastasis in the lung, and sometimes in the liver, is justified when the primary tumour is controlled. Good results can be achieved with this approach in osteosarcoma12 and nephroblastoma.13 Multiple small peripheral lung metastases can be treated simultaneously by wedge resections, preferably via bilateral thoracotomies rather than midline sternotomy which carries a risk of mediastinitis. Segmentectomy or lobectomy should be reserved for solitary centrally located lung metastases. It is also possible to resect a solitary liver metastasis located in one lobe.

Supportive care

The surgeon has a role in facilitating treatments given by other members of the oncology team. For example, surgeons and/or anaesthetists are frequently asked to insert intravenous devices for chemotherapy or parenteral nutrition (Broviac or Hickman catheters, implantable ports) either percutaneously or surgically.

When radiotherapy is necessary, the surgeon may insert a mesh to displace the bowel out of the radiation field, or displace the ovaries by transposition either to the midline behind the uterus for the inverted field used in Hodgkin disease or to the paracolic areas for external beam radiotherapy or brachytherapy of pelvic tumours. This transposition can be performed using laparoscopic surgery, as in adults.14

Organ-sparing surgery

Because of the increasing concern about long-term sequelae in young adults treated for cancer in childhood, the worldwide trend in surgical oncology is to perform organ-sparing surgery. For instance, in nephroblastoma the standard operation for unilateral nephroblastoma is total uretero-nephrectomy. In synchronous bilateral tumours, surgery is planned after tumour reduction with chemotherapy, and nephron-sparing surgery (e.g. partial nephrectomy) is considered, when feasible, to preserve renal function. The risk of very long term consequences of renal hyperfiltration after nephrectomy has led some surgeons to perform partial nephrectomy in unilateral nephroblastoma.15 This approach is not recommended in the current SIOP and NWTS protocols, except where there are contralateral urologic or nephrologic disorders or in genetic syndromes with an increased risk of Wilms tumour.

Conclusion

Surgery in paediatric oncology has changed considerably in recent years, partly because of progress in surgical and anaesthetic techniques but mainly because of an increasing interest by surgeons in the total management of the patient, with increasing involvement in establishing new multimodality treatment strategies with oncologists and other specialists. This will continue to be the best way to improve the outcome of these children not only in terms of survival, but also in terms of achieving normal life with minimal long-term sequelae.

References

1. Perilongo G, Shafford EA (1999). Liver tumours. Eur J Cancer 35, 953–9.

2. Ritchey ML, Kellalis PP, Breslow N, et al. (1992). Surgical complications after nephrectomy for Wilms tumour. Surg Gynecol Obstet 175, 507–14.

3. Godzinski J, Tournade MF, de Kraker J, et al. (1998). Rarity of surgical complications after postchemotherapy nephrectomy for nephroblastoma. Experience of the International Society of Pediatric Oncology—trial and study SIOP-9 Eur J Pediatr Surg 8, 83–6.

4. Valla JS (2001). Testis sparing surgery for benign testicular tumours in children. J Urol 165, 2280–3.

5. Cass DL, Hawkins E, Brandt ML, et al. (2001) Surgery for ovarian masses in infants, children and adolescents: 102 consecutive patients treated in a 15-year period. J Pediatr Surg 36, 693–9.

6. Rubie H, Hartmann O, Michon J, et al. (1997) N-myc amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. J Clin Oncol 15, 1171–82.

7. Rubie H, Michon J, Plantaz D, et al. (1998) Unresectable neuroblastoma: improved survival after primary chemotherapy including carboplatin-etoposide. Br J Cancer 77, 2310–17.

8. Cecchetto G, Guglielmi M, Inserra A, et al. (2001). Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17, 532–4.

9. Haie-Meder C, Breton-Callu C, Oberlin O, et al. (2000). Brachytherapy in the treatment of vesico-prostatic rhabdomyosarcomas in children. Cancer Radiother 4, 145–9.

10. Martelli H, Haie-Meder C, Oberlin O (2003). Conservative surgery + brachytherapy treatment in very young boys with bladder-prostate rhabdomyosarcoma: a single team experience. Med Pediatr Oncol 41, 260.

11. Godzinski J, Flamant F, Rey A, Praquin MT, Martelli H (1994). Value of postchemotherapy bioptical verification of complete clinical remission in previously incompletely resected (stage I and II pT3) malignant mesenchymal tumors in children: International Society of Paediatric Oncology 1984 Malignant Mesenchymal Tumour Study. Med Pediatr Oncol 22, 22–6.

12. Tabone MD, Kalifa C, Rodary C, et al. (1994). Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol 12, 2614–20.

13. Godzinski J, Tournade MF, de Kraker J, et al. (1991). Stage IV nephroblastoma with extrapulmonary metastatic involvement in SIOP 6 and 9 study. Med Pediatr Oncol 19, 371.

14. Morice P, Castaigne S, Haie-Meder C, et al. (1998). Laparoscopic ovarian transposition for pelvic malignancies: indications and functional outcome. Fertil Steril 70, 956–60.

15. Cozzi DA, Schiavetti A, Morini F, Castello MA, Cozzi F (2001). Nephron sparing surgery for unilateral primary renal tumor in children. J Pediatr Surg 36, 362–5.



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