PEDIATRIC SURGERY

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UPDATE ON SOLID TUMOR MANAGEMENT IN CHILDHOOD Stephen J. Shochat, MD

Over the past decade, there has been a marked improvement in the prognosis for children with malignancies because of the development of multimodality therapy, the institution of pediatric cancer centers, and the formation of cooperative pediatric oncology groups. Approximately 60% of children are now being cured of their disease compared with 20% a few decades ago. 19 Pediatric surgeons have continued to play an important role in this improved survival, but their role has become much more complex: the surgeon now must be familiar not only with the natural history of the tumor and the basic principles and side effects of its resection but also with new developments in the fields of diagnostic radiology, histopathology, radiation therapy, chemotherapy, and immunotherapy. Because the basic goal of multimodality therapy in children is the cure of disease with preservation of function, the pediatric surgeon should avoid mutilating procedures if at all possible. This can usually be accomplished if the operation is carefully integrated into a combined program of chemotherapy and radiation therapy. Malignant solid tumors such as eNS tumors, lymphomas, and soft-tissue sarcomas account for the majority of cancers in children, and approximately 4000 new cases are diagnosed yearly.38 The management of selected solid tumors is discussed here with emphasis on surgical diagnostic techniques, staging, and operative therapy of the primary tumor. NON-HODGKIN'S AND HODGKIN'S LYMPHOMA Biopsy

The diagnosis of non-Hodgkin's or Hodgkin's lymphoma in children presents a special challenge to the surgeon. Diagnostic biopsy requires careful From the Division of Pediatric Surgery, Department of Surgery, Stanford University Medical Center, Stanford, California

SURGICAL CLINICS OF NORTH AMERICA VOLUME 72 • NUMBER 6 • DECEMBER 1992

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planning to avoid undue morbidity while obtaining satisfactory tissue for the pathologist so that adequate therapy can be planned. Prior to the biopsy, consultation with the pediatric oncologist and pathologist should be carried out so that the appropriate diagnostic information can be obtained, as improper handling of material will necessitate a second biopsy. Peripherallymphadenopathy is frequently present, but a common error is to biopsy only the most superficial lymph nodes, which are frequently hyperplastic, whereas the pathologic nodes are often deeper within the neck or axilla. Although radical lymphadenectomy is not indicated, occasionally, an incisional biopsy of a very large node deep within the neck or axilla will be required. Special care needs to be taken in these cases in order to avoid injury to vital structures. Frozen sections should be examined if any doubt exists concerning the adequacy of the specimen. Proper handling and fixation of biopsy material is critical if the correct diagnosis is to be made. The surgeon should obtain fresh tissue for immunophenotyping, flow cytometry, cytogenetics, and touch preparations as well as for placement in fixative for routine histopathology study and possible electron microscopy.21 The best practice is to give the tissue directly to the pathologist so that. appropriate fixation and processing can be carried out. If this is impossible, the specimen should be placed in saline and sent to the pathologist with the appropriate history to ensure that the tissue will be processed appropria tely. Children with mediastinal lymphoma can be difficult to manage, especially if they present with respiratory symptoms or severe vena caval obstruction. Acute clinical deterioration and cardiopulmonary arrest have occurred after endotracheal intubation in these children. 11 Children with suspected lymphoma presenting with obvious lymphadenopathy should always have a chest radiograph to identify mediastinal involvement before undergoing general anesthesia for node biopsy or other procedures. The evaluation should always include a peripheral blood smear to check for evidence of bone marrow invasion. Even in the presence of a normal peripheral blood smear, many oncologists would recommend a bone marrow aspiration as the initial diagnostic procedure. If a pleural effusion is present, a thoracentesis should be performed for diagnostic and immunologic studies. Typicallymphoblasts are usually seen on appropriate cytocentrifuge preparations. Because normal lymphoblasts can be seen in a chylous effusion, immunohistologic studies will be necessary to confirm a malignancy. Enlarged peripheral lymph nodes are frequently seen in children with mediastinal lymphoma, and an attempt should be made to biopsy these nodes under local anesthesia if the bone marrow and thoracentesis do not reveal the etiology of the mass. Occasionally, it may be necessary to biopsy the mediastinal mass, and this can be performed by mediastinoscopy, anterior mediastinotomy, or thoracoscopy, depending on the size and age of the child. An occasional child with a mediastinal mass presents with acute respiratory compromise and superior vena caval syndrome in the absence of other involvement. Because of the hazards of anesthesia in these children, alternate forms of tissue sampling such as CT-guided needle biopsy should be carried out. In a few patients, emergency steroid or radiation therapy will be required to shrink the mediastinal mass prior to biopsy. This measure may complicate the histopathologic diagnosis at a later date, but it does not seem to affect the ultimate prognosis, as demonstrated by Loeffler et al. 23 Shamberger et aP' suggest the use of a CT scan to determine the tracheal cross-sectional area prior to biopsy to avoid potential anesthetic complications. Evaluation of these children requires very careful coordination between the surgeon, anesthesiol-

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ogist, pediatric oncologist, and pathologist if life-threatening complications are to be avoided. Role of Staging Laparotomy

Staging laparotomy for Hodgkin's disease was introduced by Kaplan in 1968 in order to determine the presence or absence of abdominal disease and to plot the exact distribution of lymph node involvement for proper design of portals for the radiation that was the primary mode of therapy at the time.1O The advisability of staging laparotomy in childhood Hodgkin's disease is now controversial, because the majority of children will receive multiagent chemotherapy in order to decrease the deleterious effect of radiation on the musculoskeletal system. This change in management may obviate knowing the exact extent of involvement. In addition, a significant morbidity and mortality rate has been associated with staging laparotomy, and a relatively high incidence of overwhelming sepsis has been reported in the asplenic child who has had Hodgkin's disease. A new observation is the surprising risk of secondary acute myelogenous leukemia following splenectomy in patients who are receiving combination chemotherapy with nitrogen mustard, vincristine, procarbazine, and prednisone. 37 As the management of patients with Hodgkin's disease continues to evolve, the indications for staging laparotomy are decreasing. Staging laparotomy currently is performed with the following exceptions: (1) clinical stage IV disease; (2) positive percutaneous bone marrow biopsy; (3) clinical stage IA disease high on the right side of the neck with lymphocyte-predominant histology that will be treated with high-dose radiation therapy alone; (4) clinical stage IA or II Hodgkin's disease confined to the thorax in older children who have a negative lymphangiogram and whose family agrees to high-dose extended-field radiotherapy; and (5) supradiaphragmatic disease with a clearly positive lymphangiogram in patients in whom the radiation therapy field would not be altered by the findings at staging laparotomy. A review of 109 staging laparotomies for pediatric Hodgkin's disease (15 years of age and younger) at Stanford University revealed no deaths and negligible morbidity. The clinical stage was changed in 36% of the patients, 26% being upstaged and 11 % being downstaged. Forty percent of the laparotomies were positive, and in 20%, the spleen was the only site of Hodgkin's disease found within the abdomen. Postsplenectomy, there were four deaths among 11 patients with overwhelming sepsis. All but one case of overwhelming sepsis occurred before the use of pneumococcal vaccine and penicillin prophylaxis. In the one patient who should have benefited from the prophylactic regimen, there was a question about the extent of compliance with penicillin prophylaxis. In addition, at the time of septicemia, the child was neutropenic following chemotherapy. This patient survived. On the basis of the above findings and of the chance of missing splenic involvement in more than 10% of patients following partial splenectomy,5 total splenectomy is still performed in those patients undergoing staging laparotomy. Pneumococcal and Haemophilus influenzae vaccines now are given prior to staging laparotomy, and penicillin prophylaxis is continued indefinitely in the postoperative period. Routine staging laparotomy is not indicated for patients with non-Hodgkin's lymphoma, as they can be staged by noninvasive studies. However, approximately one third of patients with abdominal non-Hodgkin's lymphomas present with lesions localized to the intestine. 21 Such disease can result in acute

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intestinal obstruction secondary to an intussusception or in association with an abdominal mass. The obstruction should be treated by surgical resection of the involved bowel with its associated mesentery. Further staging is not indicated unless suspicious nodes or liver involvement are present. The overall survival rate in this group of patients exceeds 80%.21, 22 The majority of children who present with intussusception and localized lymphoma have an ileocolic intussusception and are over the age of 3, the peak age being between 8 and 12 years.' Hydrostatic reduction is usually unsuccessful; if it is successful, it usually is diagnostic and reveals a filling defect in the ileum. A high index of suspicion is required when dealing with older children with intussusception, especially now that the outlook for localized non-Hodgkin's lymphoma is so favorable. Laparotomy is not indicated for children with extensive abdominal nonHodgkin's lymphoma of the Burkitt's type and, in fact, is associated with a significant morbidity and mortality rate. The majority of these patients can be staged by noninvasive studies, and no efficacy has been documented for cytoreductive or debulking procedures. 16, 36

WILMS' TUMOR

Wilms' tumor is a classic model of modern multidisciplinary treatment of childhood malignancies. The organization of the National Wilms' Tumor Studies (NWTS) has served as a prototype for other collaborative studies of childhood tumors, and the pathologic classification of Wilms' tumor and its effect on therapy and prognosis is being used as a guide in the study of various childhood malignancies. The surgical treatment recommended by the NWTS remains as initially described. A radical nephrectomy through a generous transabdominal approach should be done, which allows lymph node sampling of the para-aortic region, mobilization of the contralateral kidney with biopsy of any suspicious areas, and, if possible, isolation of the hilar vessels prior to mobilization of the primary tumor. However, in patients with very large tumors, initial isolation of the hilar vessels can be difficult, even hazardous, and has been associated with injuries to the mesenteric and celiac vessels, especially on the left side. The tumor bed and any areas suspicious for metastases should be marked with titanium clips, which will not interfere with future CT scanning. Recently, 145 patients registered on NWTS-II and NWTS-III who had synchronous bilateral Wilms' tumors were reviewed,! and the following recommendations were derived. Following a transperitoneal incision, both tumors are biopsied, and lymph node sampling is accomplished. Complete excision of both tumors is desirable if two thirds or more of the total renal parenchyma can be preserved and nephrectomy can be avoided. Chemotherapy is administered according to the stage of the most advanced lesion using NWTS-IV protocols. A second-look procedure is carried out within 6 months after the initial operation. Partial nephrectomy or excisional biopsy is performed at this procedure if it appears that all tumor can be removed. If complete excision is not possible, nephrectomy again is deferred, biopsy is repeated, chemotherapy is continued, and radiation therapy is added. A third operative procedure should be performed within the next 6 months, and bilateral renal-preserving procedures should be carried out if possible. Nephrectomy and contralateral partial nephrectomy, excisional biopsy, bench surgery, or, as a last resort, bilateral nephrectomy should be considered at this time. In patients with

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tumors of unfavorable histology, a more aggressive chemotherapy and radiation therapy regimen should follow the initial operative procedure and a more radical procedure performed at the second operation with the aim of removing all tumor. Vena Caval and Hepatic Involvement

Vena caval and atrial involvement by Wilms' tumor was studied in 77 children. 30 The survival rates were comparable stage by stage with those of children without intravascular involvement. Although the morbidity of the primary surgical excision was significant, no surgical deaths were reported. Excision of the primary tumor and thrombus is still recommended when technically feasible. If possible, the location of the thrombus should be determined prior to operation. For infrahepatic lesions, an intra-abdominal approach is sufficient, with extraction of the thrombus after proximal and distal control of the vena cava has been obtained. The use of a Fogarty or Foley balloon catheter may be required. A thoracoabdominal incision or exposure of the inferior vena cava as it enters the atrium through the membranous portion of the diaphragm is recommended for suprahepatic thrombi. The vena cava is occluded at the atrium, and the thrombus can then be removed through an infrahepatic vena caval incision. Patients with atrial extension may require cardiopulmonary bypass for thrombus removal. In these patients, a midline abdominal incision with a median sternotomy should be considered. However, a recent review of preoperative chemotherapy in children with vena caval or atrial extension revealed no embolic complications, and the majority of patients with atrial extension did not require cardiopulmonary bypass (Ritchey ML, Kelalis PP, Haase GM, et aI, manuscript submitted). Although preoperative chemotherapy can have adverse effects on subsequent staging (see below), patients with vena caval, and certainly those with atrial, extension should be considered for preoperative treatment. Hepatic involvement associated with Wilms' tumor has been considered to be a very poor prognostic sign. However, a review of the first three NWTS series does not support this contention. 37 The overall survival rates of 82% in children with liver invasion and 61 % in those with liver metastases compare favorably with the overall NWTS experience. Extensive hepatic resection in conjunction with radical nephrectomy is rarely required in these patients and should be reserved for selected cases. Role of Preoperative Chemotherapy

One of the main controversies facing the multidisciplinary team caring for children with Wilms' tumors is whether to embark on a course of preoperative chemotherapy, as suggested by the International Society of Pediatric Oncology (SIOP).3 Preoperative chemotherapy will have significant adverse effects on staging and histologic evaluation, which could lead to overtreatment or undertreatment. Evidence for this comes from the higher incidence of infradiaphragmatic relapses in those patients in the SlOP trial who did not receive postoperative radiation therapy" which suggests that although preoperative chemotherapy partially destroyed the evidence of perinephric tumor extension or lymph node involvement, it did not completely ablate microscopic disease. Subsequent SlOP studies have added an anthracycline to the chemotherapeutic

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regimen, but this drug has potentially significant cardiotoxic side effects. The end result of the analysis of preoperative chemotherapy effects in the SlOP studies is the use of more intensive chemotherapy in twice the number of patients with disease of favorable histology in stages I through III as in NWTS without decreasing the number of patients receiving radiation therapy. There also is no evidence that preoperative chemotherapy will facilitate subsequent renal-sparing operations in a significant number of patients. The data indicating hyperfiltration syndrome after unilateral nephrectomy are not well substantiated, and the incidence of tumor rupture at the time of operation in NWTS is quite low. On the basis of the above evidence, the only patients who would seem to benefit from preoperative chemotherapy are those with bilateral Wilms' tumors, those with vena caval involvement, and those with massive inoperable tumors. If bilateral Wilms' tumors are to be treated preoperatively, pathologists familiar with needle biopsy specimens must confirm the diagnosis histologically, and both sides must be sampled because of the 4% chance that a tumor with unfavorable histology will be found on one side. A difficulty in patients with vena caval involvement is that preoperative therapy may make extraction of the tumor thrombus more difficult. The number of patients with truly inoperable Wilms' tumor is hard to ascertain, as only 5% of patients registered on NWTSIII were classified as having inoperable disease. Exploration of Contralateral Kidney

A minor controversy in the surgical management of children with Wilms' tumor is the need for routine exploration of the contralateral kidney. Many surgeons and oncologists urge the continuation of this practice because small lesions can be missed even with newer imaging studies. Evidence gained from the study of bilateral Wilms' tumors supports this practice, as the smaller of the lesions found at the time of exploration not infrequently proved to be an unfavorable histologic variant. If the kidney had not been mobilized and biopsied, this important information would not have been obtained. Surgical Complications

Small-bowel intussusception is a rare but difficult complication of the resections of large retroperitoneal masses, such as by radical nephrectomy for Wilms' tumor or excision of retroperitoneal sarcomas or neuroblastomas. 26 Intussusception is seen in the immediate postoperative period and may be difficult to differentiate from ileus or partial small-bowel obstruction secondary to adhesions. An upper gastrointestinal series seems to be the best diagnostic modality, but a high index of suspicion is also of prime importance. Chemotherapy is frequently begun in the early postoperative period, and nausea, vomiting, and abdominal pain may erroneously be attributed to this therapy; undue delay in treatment will occur unless the possibility of a small-bowel intussusception is considered. NEUROBLASTOMA

The surgeon's role in the treatment of neuroblastoma has become better defined as large groups of patients with various stages of disease have been

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evaluated carefully by the collaborative pediatric oncology groups. Most of the patients with disseminated disease do not require initial major surgical intervention, as metastatic disease is easily diagnosed by imaging studies, bone marrow biopsy, or extracavitary biopsy. However, careful surgical staging should be done in patients without disseminated disease. If possible, the primary tumor should be totally excised and careful lymph node sampling performed. Children who have primary intra-abdominal tumor should have a liver biopsy. The possible exception is the very young infant without grossly obvious metastases. When there is large bulky disease that is clearly nonresectable, a biopsy should be performed, and a delayed primary or a secondlook procedure should be carried out following chemotherapy, radiation therapy, or both. There is no obvious advantage to debulking or cytoreductive surgery in this disease.25 In children with metastatic disease, the primary tumor should be removed if all metastatic sites can be controlled with chemotherapy prior to delayed primary surgery. The Pediatric Oncology Group (POG) reviewed 101 children with stage A neuroblastoma who had complete gross excision of the primary tumor with or without microscopic residual deposits. 29 The overall disease-free survival rate at 2 years was 89%. Nine patients suffered relapses, but six were salvaged with chemotherapy. There were 55 children under 1 year of age and 46 greater than 1 year of age. There was an almost equal distribution between thoracic and abdominal primaries. Patients with microscopic residual disease fared as well as those without. Thoracic tumors and low serum lactic dehydrogenase concentrations were significantly more common in stage A than in other stages. The surgical morbidity rate was 10%, and there were no operative deaths. Six nephrectomies were performed in order to remove all gross disease. This study clearly demonstrates the efficacy of complete surgical excision but does not justify supraradical or mutilating operations in order to remove all gross disease. The role of surgery in metastatic neuroblastoma was reviewed by the Children's Cancer Study Group,25 showing that survival was dependent on resolution of metastases rather than on the resectability of the primary tumor. Partial excision or debulking procedures were not efficacious. It was recommended that excision of the primary tumor not be contemplated until all metastases have been eradicated by chemotherapy or radiation therapy. Another possible treatment for metastatic neuroblastoma now being investigated is delayed primary surgical excision followed by bone marrow transplantation. This regimen includes induction chemotherapy, delayed surgery, local irradiation, and intensive chemoradiotherapy followed by infusion of allogeneic or autologous marrow. There was a 57% survival rate with a median follow-up of 32 months following transplantation. 27 However, late recurrent disease is being seen with increasing frequency. The Pediatric Oncology Group has identified a group with an intermediate prognosis that includes all children of any age with localized but unresectable disease (POG stage B) and infants less than 1 year of age with regional or widely disseminated tumor (POG stages C and D). A protocol based on the DNA index was instituted for this group of patients, and the preliminary survival rate is approximately 70%. In future protocols, the surgeons must be aware of the importance of biologic studies so that appropriate material is obtained. The application of tumor markers in the treatment of neuroblastoma may better define the role of the surgeon in the years to come. Mass screening of urine for catecholamine metabolites, as is being carried out in Japan, may identify children with low-stage disease so that surgical resection can be carried out prior to dissemination. 23• 2B

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SOFT-TISSUE SARCOMA

Soft-tissue sarcomas are relatively rare in children, representing 6% of childhood malignancies. More than half of these children will have rhabdomyosarcomas. Once again, a multidisciplinary approach is important in management. The utilization of new imaging studies such as MR and CT scanning has made the initial evaluation of these patients more precise so that the management can be planned carefully before initiating therapy. The surgeon must consider innovative operations that can accomplish total excision of the tumor without radical mutilation that will significantly affect long-term function. This is especially important for tumors that are not responsive to chemotherapy or radiation. Consultation with the radiotherapist prior to surgery is important if brachytherapy or intraoperative radiation is being contemplated to control local disease. Consultation with the pathology department is important so that an accurate diagnosis concerning tumor type is made and also so that the presence of favorable and unfavorable histology can be determined, as this will significantly affect future therapy. Accurate procuring and processing of tissues is imperative in order to obtain satisfactory electron microscopic, immunohistology, and cytogenetic studies, which may be important in planning therapy and establishing the prognosis. An incisional biopsy is usually indicated, as it is difficult to predict the exact histologic type of a soft-tissue sarcoma preoperatively. The use of needle biopsy techniques should be considered and may be preferable to incisional biopsy in certain circumstances. The non-rhabdomyosarcoma soft-tissue tumors are the malignant schwannoma, synovial-cell sarcoma, undifferentiated sarcoma, malignant fibrous histiocytoma, fibrosarcoma, leiomyosarcoma, spindle-cell sarcoma, and angiosarcoma. All of these tumors are treated in a like manner, and wide surgical excision comprises the initial management. Limb-sparing procedures are encouraged, and radical mutilating operations should be reserved for those rare patients in whom local control cannot be obtained otherwise. In a recent review from the Dana-Farber Cancer Institute, there was a 75% lO-year overall survival rate. 2 The primary site of the tumor, its histology, and the use of systemic chemotherapy exerted no significant impact on survival. The size of the tumor and the presence of gross residual disease did have a significant impact on the local control rate and hence on survival. A more aggressive treatment of local disease in the form of higher doses of radiation, brachytherapy, and re-excision was recommended as a means of improving survival in this group of patients. Regional node dissection is appropriate for clinically enlarged nodes and in cases in which the primary procedure is in juxtaposition to nodes. Regional nodes should be sampled in extremity lesions if node dissection is not planned. Proximal nodes should be sampled before proceeding with axillary or inguinal lymph node dissection. Significant improvement in survival has been achieved by utilizing combined-modality therapy in children with rhabdomyosarcoma, and the 5-year survival rate now approaches 70%.24 One of the problems in evaluating various treatment programs has been the grouping system used by the Intergroup Rhabdomyosarcoma Study compared with a TNM system, as used by the Europeans. The Intergroup system is based primarily on the extent of the disease and the type of surgery performed rather than on the biology and natural history of the tumor. Alternative staging systems have been proposed and may facilitate comparison of European and American study results. The proposed staging system will incorporate the site and size of the tumor and the presence or absence of favorable or unfavorable histology. 6,20

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Surgical management of children with rhabdomyosarcoma depends on the location of the primary lesion. The results of treatment for head and neck primary tumors have been excellent. This treatment consists of biopsy followed by chemotherapy. Complete surgical excision is rarely possible, and radical procedures such as orbital exenteration are not recommended. Trunk and retroperitoneal tumors should be treated with complete excision whenever possible. Delayed primary excision following initial biopsy, chemotherapy, and radiation therapy may also be required. Unfortunately, the survival statistics in this group of patients are poor, as the majority of these tumors are large, have an incomplete response to chemotherapy and radiation, and usually cannot be resected completely. Children with primary rhabdomyosarcomas of the extremity should also be treated by complete surgical excision if at all possible. Amputation is not warranted, as this does not seem to improve survival. Unfortunately, the prognosis is poor in this group of patients, presumably because of the high incidence of alveolar tumor histology. En bloc excision of muscle groups should be considered, as well as radiation therapy or brachytherapy. Because there is a 17% incidence of lymph node involvement at the time of diagnosis,'5 a biopsy of the regional lymph nodes should be included as part of the initial evaluation. Delayed primary excisions or re-excisions of residual tumor should be performed as long as limb function can be preserved. The main controversy concerning children with rhabdomyosarcoma is in tumors of the genitourinary tract. An important goal in these patients is to salvage organs, and the results have been both encouraging and discouraging, depending on the organ involved. The overall survival and organ salvage rates are excellent in children with vaginal and vulvar primary h.).mors. '4 Pelvic exenteration is not necessary, and hysterectomy is reserved for those children with involvement of the proximal portion of the vagina. An important consideration is relocation of the ovaries to avoid sterility from radiation therapy. Vulvar lesions respond nicely to chemotherapy, and total local excision has not been a difficult problem. Radiation or brachytherapy, again, should be considered in children with vaginal rhabdomyosarcomas. Young children with upper vaginal or uterine lesions should be treated as having vaginal primaries, because primary uterine sarcomas occur in older adolescent or postadolescent females. Primary uterine tumors seem to present as two distinct groups: polypoid lesions, in which there is a good response to chemotherapy and hysterectomy can be avoided, and extensive uterine infiltration and penetration into the abdominal cavity, in which hysterectomy followed by radiation and intensive chemotherapy may be indicated as the initial mode of therapy. Treatment of boys with para testicular rhabdomyosarcomas is by radical orchiectomy with high ligation of the spermatic cord followed by ipsilateral radical lymph node dissection. Despite the fact that retroperitoneal node involvement occurs in approximately 40% of these children, their prognosis is excellent. '7 The most difficult problem in the treatment of children with genitourinary rhabdomyosarcomas is the management of bladder and prostatic tumors. Exenteration followed by chemotherapy and possible radiation was the initial mode of therapy, but in recent years, preoperative chemotherapy and radiation followed by delayed surgery has been tried in attempts to preserve bladder function. While the overall survival statistics are good, only a third of the patients retained all or part of the bladder intact.13 Radical prostatectomy12 and partial cystectomy17 should be considered in these patients. If definitive surgical resection is not anticipated following radiation and chemotherapy, extremely close surveillance for recurrence is imperative if these children are to be salvaged by anterior exenteration.

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HEPATIC TUMORS

Hepatic tumors are rare in children, accounting for less than 5% of intraabdominal malignancies. Hepatoblastomas occur in infancy, and the majority are seen prior to 3 years of age. The other main histologic type is hepatocellular carcinoma, which has two age peaks, one prior to 4 years and another between 12 and 15 years. Approximately 70% of all hepatic tumors in children are malignant. 8 While a multimodality approach continues to be important in this malignancy, the surgeon plays a significant role because complete surgical removal is imperative for long-term survival. The survey conducted by the American Academy of Pediatrics Surgical Section in 1974 found no survivors among 227 patients in whom there was incomplete removal of the primary tumor. 8 Unfortunately, only approximately 50% of children with hepatoblastomas have completely resectable disease at diagnosis. 8 A recent observation that hepatoblastomas can have favorable and unfavorable histology makes surgery even more important. The survival rate of patients with favorable-histology hepatoblastoma is in excess of 90%!· 18 Following the initial evaluation, which should include CT scan or MR and arteriography, preparations should be made for exploratory laparotomy and total removal of the primary tumor. Because it is difficult to determine resectability prior to a laparotomy, all patients should have a formal exploration unless it is obvious from the preoperative studies that both hepatic lobes are involved or that there is a large central lesion that is not operable. If the tumor is inoperable at initial laparotomy, or prior to performing a laparotomy, chemotherapy should be given, with re-evaluation in 4 months. The primary objective in the management of these tumors should be surgical removal. At the time of laparotomy, lymph nodes should be biopsied, and the resection margin should be sampled to confirm by frozen section that removal of the tumor has been complete. Any residual tumor should be marked with titanium clips. Fibrolamellar hepatoma is a variant of hepatocellular carcinoma that has a good prognosis if it can be completely excised. 35 Adjuvant chemotherapy is not recommended for this particular tumor unless the lesion cannot be resected completely. Because surgical excision of liver tumors is of ultimate importance, the surgeon caring for these children must be familiar with the various techniques that can be used to carry out a satisfactory liver resection. Hepatic trisegmentectomy is a recognized procedure for very large tumors and is ideal for use in infants with hepatoblastoma and hepatocellular carcinoma. The use of rapidinfusion devices and hypothermia with extreme hemodilution may be necessary.33 The surgeon should also be familiar with the techniques of ultrasonic dissection, intraoperative ultrasound scanning, and the Nd:YAG laser, which can be helpful in liver resection. SUMMARY

Surgery will continue to play an important role in the multidisciplinary treatment of solid tumors in children. However, as the complexity of therapy increases, it is imperative that the pediatric surgeon become familiar with new radiation therapy techniques, new chemotherapeutic agents, and the advances that are being made in immunodiagnosis, immunotherapy, and molecular

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biology. New markers for various tumors are being discovered and have therapeutic and prognostic value that may have a significant impact on surgical therapy. New protocols are being developed within the various cooperative research groups, and the surgeon must participate actively, so that surgical questions of importance can be answered and so that adequate tissue specimens can be obtained for future investigations. References 1. Blute ML, Kelalis PP, Offord KP, et al: Bilateral Wilms' tumor. J Urol138:968, 1987 2. Brizel OM, Weinstein H, Hunt M: Failure patterns and survival in pediatric soft tissue sarcoma. J Radiat Oncol BioI Phys 15:37, 1988 3. D'Angio GJ: SlOP and the management of Wilms' tumor. J Clin Oncoll:595, 1963 4. D'Angio GJ, Breslow N, Beckwith JB, et al: The treatment of Wilms' tumor: Results of the Third National Wilms' Tumor Study. Cancer 64:349, 1989 5. Dearth JC, Gilchrist GS, Telander RL, et al: Partial splenectomy for staging Hodgkin's disease: Rise of false-negative results. N Engl J Med 299:345, 1978 6. Donaldson SS, Belli JA: A rational clinical staging system for childhood rhabdomyosarcoma. J Clin Oncol 2:135, 1987 7. Ein SH, Stephens CA, Shandling B, et al: Intussusception due to lymphoma. J Pediatr Surg 21:786, 1986 8. Exelby PR, Filler RM, Grosfeld JL: Liver tumors in children in particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey, 1974. J Pediatr Surg 10:329, 1975 9. Finegold MS, Weinberg AC: Hepatoblastoma: Histologic classification has important prognostic and therapeutic implications. Pediatr Res 17:223A, 1983 10. Glatsen E, Guernsey JM, .Rosenberg SA, et al: The value of laparotomy and splenectomy in the staging of Hodgkins disease. Cancer 24:709, 1969 11. Halpern S, Chatten J, Meadows AT, et al: Anterior mediastinal masses: Anesthesia hazards and other problems. J Pediatr 102:407, 1983 12. Hardy B, Green 0, Folkman J: Radical prostatectomy in an 18 month old boy [abstract]. Proceedings of the American Pediatric Surgical Association, 1978, p 75 13. Hays OM, Raney RB Jr, Lawrence W Jr, et al: Primary chemotherapy in the treatment of children with bladder-prostate tumors in the Intergroup Rhabdomyosarcoma Study (IRS-II). J Pediatr Surg 17:812, 1982 14. Hays OM, Shimada H, Raney RB, et al: Clinical staging and treatment results in rhabdomyosarcoma of the female genital tract among children and adolescents. Cancer 61:1893, 1988 15. Heyn R, Hays 0, Lawrence W: Extremity alveolar rhabdomyosarcoma and lymph node spread: A preliminary report from the Intergroup Rhabdomyosarcoma Study (IRS-II) [abstract]. Proc Am Soc Clin Oncol 3:80, 1984 16. Kaufman BH, Burgery EO, Banks PM: Abdominal Burkitt's lymphoma: Role of early aggressive surgery. J Pediatr Surg 22:671, 1987 17. Lacey SR, Jewett TC, Karp MP, et al: Advances in the treatment of rhabdomyosarcoma. Semin Surg OncoI2:139, 1986 18. Lack EE, Naeve C, Vawter GF: Primary hepatic tumors in childhood. Hum Pathol 14:512, 1983 19. Lampkin BD, Wong KY, Kalcinyak KA, et al: Solid malignancies in children and adolescents. Surg Clin North Am 65:1351, 1985 20. Lawrence W, Gelan EA, Hays OM, et al: Prognostic significance of staging factors of IUCC staging system in childhood rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study (IRS-III). J Clin Oncol 5:46, 1987 21. Link MP: Non-Hodgkin's lymphoma in children. Pediatr Clin North Am 32:699, 1985 22. Link MP, Donaldson SS, Bernard CW, et al: High cure rate with reduced therapy in localized non-Hodgkin's lymphoma of childhood [abstract]. Proc Am Soc Clin Oncol 6:190,1987 23. Loeffler JS, Leopold KA, Recht A, et al: Emergency prebiopsy radiation for mediastinal

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24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38.

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Address reprint requests to Stephen J. Shochat, MD Division of Pediatric Surgery Department of Surgery Stanford University Medical Center S-067 Stanford, CA 94305