Hepatic metastasectomy in children.

BACKGROUND: There are little data regarding the safety and efficacy of hepatic metastasectomy for solid tumors in childhood. We reviewed our institutional experience to assess operative mortality and morbidity, technique of resection, local control, and survival in pediatric patients undergoing liver resection for metastases. METHODS: All pediatric patients who underwent hepatic resection for metastatic disease from August 1988 to July 2005 were retrospectively identified and clinical data were collected. RESULTS: Fifteen patients were identified during this period and primary malignancies included neuroblastoma (7), Wilms tumor (3), osteogenic sarcoma (2), malignant gastric epithelial tumor (1), and desmoplastic small round cell tumor (2). Twelve patients underwent anatomical hepatic resections and 3 had wedge resections. There were no intraoperative or postoperative deaths. The 2 postoperative complications included 1 wound infection and 1 bile collection. The median follow-up after hepatic resection was 1.6 years (0.2-7 years). Three patients remain alive. Eleven patients died of progressive disease; 4 patients suffered local recurrence. One patient died from enterocolitis and sepsis and was without evidence of malignancy at the time of death. CONCLUSIONS: Hepatic metastasectomy in children is feasible and is associated with a low operative mortality and morbidity. In this small group of patients anatomic hepatectomy was associated with better local control compared with wedge resection. Overall prognosis in these patients remains poor and the decision to perform hepatic metastasectomy should be highly selective.

The management of treatment-related esophageal complications in children and adolescents with cancer.

BACKGROUND AND PURPOSE: Serious treatment-induced esophageal strictures and tracheoesophageal fistulae are rare in the pediatric oncology population. This report details our experience with their management. METHODS: We retrospectively reviewed our experience with pediatric oncology patients treated for esophageal complications over a 23-year period. Serious complications were defined as development of strictures requiring dilatation or an esophageal fistula. Fifteen patients were identified, 5 of which had been previously reported. RESULTS: Thirteen patients developed esophageal stricture, and 2 progressed to tracheoesophageal fistulae. The remaining 2 patients developed tracheoesophageal fistulae without antecedent stricture. The median interval from cancer diagnosis until development of esophageal complications was 3.5 years (range, 0.4-11.8 years). Before development of esophageal complication, 14 patients (93%) were treated with mediastinal radiation and 7 (47%) for candidal esophagitis. Strictures were most commonly located in the distal esophagus (5), then midesophagus (3), cervical esophagus (3) and diffusely (2). A median of 5 dilatations (range, 1-50) were necessary before patients were able to resume a normal diet. The origin of tracheoesophageal fistulae was the midesophagus (3) and distal esophagus (1). All 4 patients with fistulae were treated with esophageal division and diversion followed by esophagocoloplasty. CONCLUSIONS: Esophageal strictures and fistulae may occur because of cancer therapy in childhood. Prevention includes early treatment of esophagitis especially Candida mucositis, and minimization of radiation dose to the esophagus. Strictures usually respond to dilatation, but fistulae require esophageal diversion and secondary reconstruction.

Results of multimodal treatment for desmoplastic small round cell tumors.

PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are rare aggressive neoplasms that frequently present with large symptomatic intraabdominal masses. We examined the effects of multimodal therapy including induction chemotherapy, aggressive surgical debulking, and external beam radiotherapy on patients with DSRCT. METHODS: Institutional Review Board permission was obtained. Sixty-six patients were diagnosed by histology, immunohistochemistry, and or cytogenetics as having DSRCT at our institution from July 1, 1972, to July 1, 2003. Data were collected on patient demographics, presenting symptoms, tumor location and extent, treatment regimen, and overall survival. RESULTS: A majority of patients were male (91%), Caucasian (85%), and with a median age of 19 (7-58) years old at diagnosis. The most common presenting complaint was an intraabdominal mass (64%). In 63 patients (96%), the primary tumor was located in the abdomen or pelvis. Thirty-three (50%) had positive lymph nodes and 27 (41%) had distant parenchymal metastases at diagnosis. Overall, 3- and 5-year survivals were 44% and 15%, respectively. Twenty-nine of these patients (44%) underwent induction chemotherapy (P6), surgical debulking, and radiotherapy. Three-year survival was 55% in those receiving chemotherapy, surgery, and radiotherapy vs 27% when all 3 modalities were not used (P < .02). Gross tumor resection was highly significant in prolonging overall survival; 3-year survival was 58% in patients treated with gross tumor resection compared to no survivors past 3 years in the nonresection cohort (P < .00001). Ten patients (15%) have no evidence of disease with a median follow-up of 2.4 years (range, 0.4-11.2 years). CONCLUSIONS: Multimodal therapy results in improved survival in patients with DSRCT. Aggressive surgical resection of these extensive intraabdominal neoplasms correlates with improved patient outcome.

Positional gene expression analysis identifies 12q overexpression and amplification in a subset of neuroblastomas.

Neuroblastoma is a heterogeneous disease with variable clinical behaviors. Unique molecular features are associated with clinically relevant subgroups. We performed a comprehensive microarray gene expression analysis of 95 neuroblastomas in an effort to define clinically important molecular subtypes. A subset of tumors overexpressed several contiguous genes located at 12q13 approximately q15 and were studied further. By microarray, 5 of 95 neuroblastomas had overexpression of genes mapped to 12q13.1 approximately q15, suggesting an amplification event in this region. Positional expression mapping identified the narrowest region of overlap containing 21 genes, with 11 genes overexpressed in all five cases. Fluorescence in situ hybridization demonstrated 3 neuroblastomas with more than a 10-fold increase in 12q gene copies and 9 with 3- to 5-fold increases. Amplification and overexpression of genes at 12q13 approximately q15 were observed in a small subset of neuroblastomas. Although amplification of 12q has been previously reported in neuroblastoma cell lines, this is the first demonstration in tumor samples, and it defines a distinct subset that has not been described previously. The expressed genes mapped closely to the complex amplicon reported in sarcomas, and they identify critical genes and pathways affected by 12q gene amplification.

Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases.

PURPOSE: The surgical management of osteosarcoma patients with unilateral pulmonary nodules is controversial. The authors reviewed their institutional experience to evaluate the incidence of occult contralateral metastases. METHODS: Data were obtained retrospectively on all consecutive osteosarcoma patients from 1980 to 2002. Eighty-four patients with pulmonary nodules were identified. Forty-one had bilateral disease, and 43 had unilateral involvement by computed tomography (CT) scan. RESULTS: All 43 patients with unilateral nodules underwent ipsilateral thoracotomies. Fifteen patients had negative exploration findings, and only 1 had pulmonary relapse. Of the 28 patients with metastases confirmed at initial thoracotomies, 14 had extensive pleural or extrapulmonary disease at initial thoracotomy followed by disease progression. The other 14 are separated into early versus late metastases, using 2 years from diagnosis as the cutoff point. Seven of the 9 (78%) patients with early metastases had or subsequently had contralateral disease; 6 were identified at staged contralateral thoracotomy and 1 had relapsed in the unexplored lung a year later. Only 1 of the 5 patients with late unilateral metastases had relapse in the contralateral side. CONCLUSIONS: Our data indicate that there is a high rate of contralateral involvement in osteosarcoma patients with unilateral nodules diagnosed by CT scan. Staged bilateral thoracotomies should be considered in osteosarcoma patients presenting with unilateral pulmonary disease on imaging studies within 2 years of diagnosis.