Denis R. King

Randomized Comparison of Cisplatin/Vincristine/Fluorouracil and Cisplatin/Continuous Infusion Doxorubicin for Treatment of Pediatric Hepatoblastoma: A Report From the Children’s Cancer Group and the Pediatric Oncology Group

PURPOSE Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. PATIENTS AND METHODS Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. RESULTS There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. CONCLUSION Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.

Pediatric Head Injuries: Can Clinical Factors Reliably Predict an Abnormality on Computed Tomography?

STUDY OBJECTIVE To assess clinical features that might reliably predict the need for computed tomography (CT) imaging in pediatric head trauma. DESIGN/SETTING/TYPE OF PARTICIPANT: Prospective cohort of 324 head CT scans performed on 322 consecutive trauma patients at an urban childrens hospital. RESULTS Sixty-two percent of patients were male. The mean age was 7.1 years (10 days to 20.6 years); half were less than 5 years of age. The two most frequent mechanisms of injury were falls (32%) and motor vehicle accidents (25%). Abnormalities were detected in 74 scans. Intracranial injuries were apparent in 39 patients (12%); 16 had a concomitant fracture. An isolated cranial abnormality was observed on 35 scans (11%). Loss of consciousness, amnesia for the event, a Glasgow Coma Scale (GCS) of less than 15, and the presence of a neurologic deficit were more common in children with intracranial injury (P < .05). Vomiting, seizures, and headache were not discriminating clinical features. No single characteristic consistently identified the children with an intracranial injury. Of the 195 children who were neurologically intact (GCS, 15) at the time of presentation, 11 (5%) had evidence of intracranial pathology on CT scan. CONCLUSION This study demonstrates a poor correlation between the clinical symptoms of significant traumatic brain injury and findings on CT.

Broviac catheter sepsis: The natural history of an iatrogenic infection

Between January 1982 and December 1983, 335 Broviac catheters placed in 270 infants and children were prospectively evaluated. The average duration of catheter life was 99.7 days, yielding a total accumulated experience of 33,394 catheter days. Blood culture-proven bacteremia occurred on 77 occasions (23%), an average of one spetic episode for every 434 days of catheter use. Temperature elevation was the only consistent clinical sign of infection occurring in 91% of the children. White blood cell counts remained within the normal range in the majority of patients. The differential counts were most helpful, however, documenting a significant increase in the number of immature neutrophils. The rise in band forms was frequently observed 24 to 48 hours before the onset of clinically evident sepsis. Platelet counts did not change significantly. Eighty-eight microorganisms were identified on blood culture. Eighty-three bacterial isolates were recovered (94%) and five fungi. The vast majority of patients (86%) had a single organism on blood culture but polymicrobial sepsis was observed on 11 occasions. Staphylococcus sp (38%) and Streptococcus sp (25%) species were most common. Of particular importance, 48% of coagulase negative staphylococci were nafcillin-resistant. Of the gram negative bacteria, Klebsiella (10%) and Pseudomonas (6%) species were most frequent. In 53 patients, antibiotic therapy was administered in an attempt to salvage the catheter. Bacteremia was controlled successfully in 39 (74%), and in the other 14 children, persistent sepsis dictated catheter removal. One patient (0.4%) died as a result of catheter-related sepsis.

Diagnosis, management, and outcome of cervicofacial teratomas in neonates: A Childrens Cancer Group study

The management of cervicofacial teratomas in neonates is often complicated and may result in significant morbidity and death. A Childrens Cancer Group (CCG) retrospective study was conducted to evaluate a multiinstitutional experience with the treatment of these extremely rare neoplasms. Twenty neonates with cervicofacial teratomas, presenting from 1971 to 1994, were identified from nine CCG institutions. Fourteen neonates had cervical teratomas, and six had orofacial teratomas. There were 12 males and eight females. A diagnostic prenatal ultrasound examination was performed in six cases. Life-threatening airway obstruction occurred in seven infants (35%) in the early postnatal period. Two neonates died in the delivery room without ever having their airway secured. Two other infants with a prenatal diagnosis survived only because tracheostomies were performed by pediatric surgeons who were in the delivery room. Three other patients were orally intubated, one after sustaining hypoxic cardiac arrest. Eighteen infants had their primary tumor excised. Three patients required tracheostomy. After resection, two patients had evidence of unilateral recurrent laryngeal nerve injury, and two required prolonged thyroid hormone replacement. Histological examination showed eight mature and seven immature teratomas. Four infants (20%) clearly had malignant lesions. Pulmonary metastases occurred in two patients and contributed to one late death at 6 months of age. The overall survival rate was 85%, and the mean follow-up period was 5 years (range, 2 months to 16 years). Twelve of 17 surviving patients (70%) have had an excellent functional and cosmetic outcome. Four children have varying degrees of developmental delay and mental retardation. Hypoxia at birth was believed to have contributed to these problems in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric cervical spine fractures: Predominately subtle presentation☆

Previous description of cervical spine fractures in children have emphasized high mortality injuries to the upper cervical vertebra. Our experience suggests a much wider spectrum of injury. The medical records of all children with cervical spine fractures admitted to Childrens Hospital between January 1, 1985 and December 31, 1989 were reviewed. The average age of the 50 patients was 11 years (range, 2.7 to 18.8 years) and 62% were boys. Motor vehicle-related accidents (54%), sports injuries (18%), and falls (12%) accounted for the majority of the fractures. Twenty-nine patients (58%) had an associated head injury. Fifty percent of the patients were transported from the accident scene and 44% were interhospital transfers. All patients receiving medical care prior to referral had appropriate cervical spine stabilization. On admission 30% of the patients were unresponsive. Thirty-one children were alert and verbal at the time of evaluation and 30 complained of neck pain and tenderness (97%). Twenty-five of the 31 patients (83%) had no demonstrable neurological deficit on initial physical examination. Lateral cervical spine radiographs were diagnostic in 49 children (98%). A relatively even distribution of fractures occurred at all levels of the cervical spine. The anatomic site of the injury did not correlate with age. Sixteen patients (32%) died. Of the 34 who survived, only 6 had a persistent neurological deficit. Children with cervical spine fractures have two distinct patterns of presentation: lethal or intact. The majority of children with cervical spine fractures presented with no complaints of neck pain and/or tenderness need a complete radiographic evaluation of their cervical spine.

Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin's lymphoma: a Childrens Cancer Group study.

PURPOSE Patients with lymphoblastic non-Hodgkins lymphoma (LB NHL) were randomized to treatment with either modified LSA2L2 or ADCOMP, which added daunorubicin (DAUN) and asparaginase (L-ASP) to the methotrexate (MTX), cyclophosphamide (CYT), vincristine (VCR), and prednisone (PRED) (COMP) regimen, in a clinical trial to determine the relative effectiveness and toxicity of the two regimens. PATIENTS AND METHODS Patients with LB NHL were eligible for this randomized study if they were less than 22 years of age at diagnosis and had < or = 25% blasts in the bone marrow. Of 307 patients registered, 281 were fully eligible and assessable. Patients were stratified by extent of disease at diagnosis. RESULTS The 5-year event-free survival (EFS) rate for patients with localized disease was 84%, and for patients with disseminated disease, 67%. There were four relapses in 28 patients with localized disease. Two hundred six patients had mediastinal primary tumors and despite local radiation, 34 of 63 failures in these patients involved the primary tumor site with or without other involvement. After adjusting for extent of disease at diagnosis, the regimens did not differ significantly with respect to risk for adverse events. The acute toxicity was primarily neutropenia and thrombocytopenia, with greater initial toxicity in patients on the LSA2L2 regimen. Three patients developed acute myelogenous leukemia. CONCLUSION Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.

The surgical management of children with incompletely resected hepatic cancer is facilitated by intensive chemotherapy

This prospective study was undertaken to evaluate the efficacy of continuous-infusion doxorubicin and cisplatin (CI-DOX/CPPD) for the treatment of children with incompletely resected hepatic cancer. Of the 46 evaluable patients, 32 had hepatoblastoma (70%) and 14 had hepatocellular carcinoma. Ten children had stage II tumors (microscopic residual), 25 were defined as stage III (gross residual), and 11 had distant metastasis (stage IV). Twelve patients underwent initial incomplete resection of their hepatic lesions and in the 34 others tumor biopsy specimens were obtained. Chemotherapy was administered and the majority of the children (70%) had an excellent clinical response with a decrease in both alpha-fetoprotein levels and measured tumor dimensions. The combination of CI-DOX/CPDD clearly facilitated surgical management, allowing for delayed hepatic resections in 20 of the 34 patients (59%) whose tumors were initially biopsied and considered to be unresectable. Overall survival in this study demonstrates a significant improvement in comparison to the historical controls. Twenty-one patients (46%) remain in complete clinical remission an average of 30 months following diagnosis (range, 17 to 40 months). The outcome of the children with hepatoblastoma was much better than those with hepatocellular carcinoma (63% v 17% survival). Survival of the 20 children who underwent delayed hepatic resections was not statistically different from the 12 patients whose hepatic tumors were removed at the initial laparotomy (41% v 58% survival). Although no obvious survival advantage was observed in those patients who underwent initial hepatic resections, there did appear to be an increased risk of postoperative complications in children whose tumors were resected following chemotherapy (8% v 25%).

Pediatric cervical-spine immobilization : achieving neutral position ?

This study was designed to evaluate prospectively the ability of current spine-immobilization devices to achieve radiographic-neutral positioning of the cervical spine in pediatric trauma patients. All trauma patients who required spinal immobilization and a lateral cervical spine radiograph were included in the study. A lateral cervical spine radiograph was obtained while the child was immobilized. The Cobb angle (C2-C6) was measured using a handheld goniometer. The method of immobilization, age at injury, and Cobb angle were compared. One hundred and eighteen patients with an average age of 7.9 years were enrolled. The majority were males (71%). The most frequent mechanisms of injury included motor vehicle accidents (35%) and falls (32%). The average Glascow Coma Scale score was 14. Although 31% of the children complained of neck pain, 92% were without neurologic deficits. The Cobb angles ranged from 27 degree kyphosis to 27 degree lordosis, and only 12 of the patients presented in a neutral position (0 degrees). Greater than 5 degrees of kyphosis or lordosis was observed in 60% of the children. Thirty-seven percent of the patients had 10 degrees or greater angulation. The most frequent methods of immobilization included a collar, backboard, and towels (40%), and a collar, backboard, and blocks (20%), but these techniques provided < 5 degrees kyphosis or lordosis in only 45% and 26% of the children respectively. No single method or combination of methods of immobilization consistently placed the children in the neutral position.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative identification of parathyroid gland pathology: A new approach

Technetium 99m-sestamibi, a radiopharmaceutical used for the diagnostic imaging of abnormal parathyroid tissue, and the Neoprobe 1000, a hand-held, gamma-detecting probe, were used concurrently, during surgical exploration, in three children with hyperparathyroidism. This novel combination assisted with the identification of an ectopic mediastinal parathyroid adenoma and with the localization of multiple hyperplastic parathyroid glands. 99mTc-sestamibi combined with the Neoprobe 1000 may prove to be a useful adjunctive technique for the intraoperative localization of abnormal parathyroid tissue in selected patients.