High-dose induction chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing's sarcoma, and undifferentiated sarcoma.

PURPOSE: To improve response and survival rates in patients with high-risk rhabdomyosarcoma (RMS), extraosseous Ewing's sarcoma, and undifferentiated sarcoma, we used a short course of induction with multi-agent chemotherapy, hyperfractionated radiotherapy, and surgery when possible. Consolidation was with intensive chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Twenty-six patients (21 with RMS, three with undifferentiated sarcoma, and two with extraosseous Ewing's sarcoma) were entered onto the protocol between June 1990 and March 1994. Induction consisted of ifosfamide, etoposide, doxorubicin, dactinomycin, cyclophosphomide, and vincristine, and a split course of hyperfractionated radiotherapy. Patients who attained a complete response (CR) or good partial response (GPR) received consolidation with high-dose melphalan and etoposide followed by ABMT. RESULTS: Of 26 previously untreated patients 19 (73%) achieved a CR (n=13) or GPR (n=6) at the completion of induction and underwent ABMT. Two-year overall survival (OS) was 56% (95% confidence interval [CI], 36% to 76%) and progression-free survival (PFS) was 53% for the whole group (95% CI, 33% to 73%). CONCLUSION: Consolidation of response by myeloablative chemotherapy was well tolerated. Split-course hyperfractionated radiotherapy did not increase the rate of local control. The results of this short-course therapy were comparable to previous therapies of 1 to 2 years' duration. Induction and consolidation chemotherapy, as well as radiation dose, could be further intensified, since no death due to toxicity occurred among these patients.

Outcome of patients with a history of bilateral retinoblastoma treated for a second malignancy: the Memorial Sloan-Kettering experience.

BACKGROUND: Patients with bilateral retinoblastoma are well recognized to have a high risk of developing a second malignancy, but there are little published data regarding the outcome of these patients following treatment. PATIENTS AND METHODS: We identified 15 patients with a history of bilateral retinoblastoma who received treatment at Memorial Sloan-Kettering Cancer Center for a newly diagnosed second malignancy. The median age of second tumor occurrence was 18 years (range 10-32 years). Three patients later had a third tumor (18 tumors total). Tumor sites included facial structures in 14 cases and extremities in 4. Histologies included osteosarcoma (5), leiomyosarcoma (5), high-grade spindle cell sarcoma (3), malignant fibrous histiocytoma (3), malignant mesenchymoma (1), and angiosarcoma (1). RESULTS: Nine patients are alive: 7 disease free at a median of 29 months (range 6-214 months) and 2 with residual disease 59 and 148 months post-diagnosis of the second malignancy. Six patients have died at a median of 31 months (range 16-98 months) after diagnosis of the second malignancy. CONCLUSIONS: Patients with a history of bilateral retinoblastoma who develop a second malignancy may enjoy extended periods of survival. Aggressive therapy appropriate to the tumor histology and site is indicated.

The location and appearance of second malignancies in patients with bilateral retinoblastoma.

Purpose. This paper describes the clinical history and radiographic appearance of second malignancies in patients with bilateral retinoblastoma.Subjects/methods. The imaging studies and clinical data of 14 patients with a history of bilateral retinoblastoma who were treated for second malignancies were reviewed.Results. A total of 17 tumors were identified in 14 patients during the period 1978-1996. The median age of occurrence of the second malignancy was 17 years (range 10-32 years). Fourteen of the 17 malignancies occurred in the facial structures and three developed in the lower extremities. The histologies included osteosarcoma (n = 5), malignant fibrous histiocytoma (n = 3), high-grade spindle cell sarcoma (n = 3), malignant mesenchymoma (n = 1), leiomyosarcoma (n = 4) and angiosarcoma (n = 1). The tumors were locally aggressive and had a similar appearance to those found in nonretinoblastoma patients. Six of the 14 patients are alive and disease free.Discussion. Most of the adolescent and young adult retinoblastoma survivors developed second malignancies in the irradiated facial structures but some occurred in distal sites. Radiologically, these tumors do not differ in appearance from those seen in non-retinoblastoma patients with the exception of their location.

Liver regeneration in children after major hepatectomy for malignancy--evaluation using a computer-aided technique of volume measurement.

PURPOSE: The time course of hepatic volume regeneration and return of excretory and synthetic function was studied in eight children undergoing lobar or extended lobar liver resections for hepatoblastoma (n = 5), hepatoma (n = 1), and recurrent nephroblastoma (n = 2). Five patients received preoperative and all were administered postoperative chemotherapy. Whole-liver irradiation was administered to one patient. One additional patient who underwent an extended hepatic resection for benign disease and did not receive chemotherapy was included for comparison. METHODS: A previously validated technique of computer-aided volume measurement was used to measure liver volumes from serial CT scans obtained after hepatic surgery. Normal liver volume as a function of age was determined from the literature and the time course of regeneration was compared to normal liver growth. Postoperative serum albumin, total bilirubin, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were recorded and correlated with volume regeneration. RESULTS: In six patients hepatic regeneration had progressed to normal volume by 90 days after resection (normal volume for age was achieved by 50 days in three patients). There was an initial rapid rate of regeneration (> 10 cc/day) which declined to a normal rate of less than 0.5 cc/day at 90 days after surgery. Two children with failure to thrive displayed the same pattern of rapid regeneration, attaining a volume appropriate for weight but less than that expected for age. The shape of the liver volume regeneration curve was similar in one additional patient undergoing an extended left lobectomy for benign disease. A brief rise in bilirubin occurred during the first week and a transient fall in serum albumin was followed by resumption of normal synthetic capacity within 6 weeks in all but two patients. CONCLUSIONS: Liver regeneration in children is a rapid process occurring despite the administration of cytotoxic agents and hepatic irradiation.

Survival from locally invasive or widespread neuroblastoma without cytotoxic therapy.

PURPOSE: To test the hypothesis that cytotoxic therapy is not needed at diagnosis to assure the survival of most patients with non-stage 4 neuroblastoma. METHODS: Patients with non-stage 4 disease received no cytotoxic therapy in the absence of N-myc amplification. The International Neuroblastoma Staging System (INSS) was used. RESULTS: Of 84 consecutive patients with previously untreated, newly diagnosed neuroblastoma, 31 (37%) had non-stage 4 disease. All 31 patients initially received no cytotoxic therapy because none of them had N-myc amplification. Nine stage 1 patients are relapse-free. This report focuses on the 22 patients with locally invasive or distant disease: two stage 2A with gross residual tumor postsurgery, 11 stage 2B with ipsilateral or midline lymph node involvement, four stage 3, and five stage 4S. Eight of the 22 patients were older than 1 year. Postsurgery, 13 patients had visible residual disease, and two others had markedly increased urinary catecholamine levels for more than 1 year. Recurrent or enlarging tumors regressed spontaneously (n = 2) or were excised 5 to 39 months after diagnosis (n = 4). One of the latter had chromosome 1p deletions (common in poor-risk neuroblastoma) that were not detected in the patient's original tumor resected 23 months earlier--findings consistent with clonal evolution or multifocal disease. The patient received chemotherapy. All 22 patients are alive 24 to 98 months (median, 64) from diagnosis. CONCLUSION: Our results suggest that non-stage 4 patients without N-myc amplification can be spared cytotoxic therapy because (1) residual postsurgical or recurrent biologically favorable neuroblastoma rarely evolves into lethal stage 4 disease; and (2) neuroblastoma in lymph nodes has no prognostic significance. These findings are remarkable because no other cancer includes subtypes that are curable without therapy to ablate residual disease.

Validation of a technique of computer-aided tumor volume determination.

Tumor volume at diagnosis is an important prognostic factor and volume change may predict therapeutic response. However, the accuracy of in vivo tumor volume measurement has not been established. The purpose of this study was validation of a personal computer-based technique of in vivo volume determination. CT scans of 8 radiological phantoms and 25 neuroblastoma patients were digitized using three-dimensional reconstruction and volume determination software. Phantom volumes were calculated from known dimensions or direct measurement while tumor volumes were determined by water displacement at the time of complete gross resection. Comparison to tumor volume determination was performed using an ellipsoid geometric model. The standard deviation for computer-generated triplicate volume determinations varied from 0.1 to 5.6 cc (median = 0.6 cc). Linear regression analysis demonstrated a close correlation between computer-derived volumes and the volume measured at surgery (r = 0.99) with small variability. In contrast, the correlation coefficient between ellipsoid formula-derived and water displacement volumes was 0.93. Computer-generated tumor volume determination is reproducible, accurate, and easily obtained from hard copy scans. This technique provides a quantitative in vivo measurement for use as a prognostic or therapeutic response variable.

Congenital mesoblastic nephroma metastatic to the brain: a report of two cases.

Congenital mesoblastic nephroma was originally believed to be a universally benign neoplasm. More recently, aggressive congenital mesoblastic nephromas have been described with local recurrence and/or metastases. We report two patients with documented congenital mesoblastic nephroma which later metastasized to the brain.

Sonographic evaluation of ureterectasis in children: the significance of peristalsis.

The presence or absence of ureteral peristalsis was noted during real-time sonography of 61 dilated ureters in children. The findings were correlated with diagnoses established using standard radiographic and radionuclide imaging techniques. Of the 47 dilated ureters that exhibited peristalsis 44 were classified as not obstructed when assessed with standard imaging and functional studies. The most frequent etiology for ureteral dilatation associated with peristalsis was high grade vesicoureteral reflux (31 ureters). Three peristaltic ureters were shown to be mildly to moderately obstructed. Absence of peristalsis was noted in 14 ureters: 13 were severely obstructed, while in 1 the involved kidney had no function. In the pediatric age group the demonstration of peristalsis in a dilated ureter is frequently associated with vesicoureteral reflux and is seldom associated with obstruction. Obstruction, if present, usually is mild. Aperistaltic ureterectasis implies severe obstruction or poor renal function.

Fractures in young children. Distinguishing child abuse from unintentional injuries.

OBJECTIVE: To determine features of fractures in young children that would be helpful in distinguishing child abuse from unintentional injuries. DESIGN: Case series. SETTING: Pediatric Services of Yale-New Haven (Conn) Hospital (a tertiary care center). PATIENTS: Consecutive children who were less than 3 years of age and who were examined for a fracture from January 1979 through December 1983 were identified from the daily logs of the emergency department or the hospital's child abuse registry. OUTCOME MEASURE: Each case was rated, by means of predefined criteria and a consensus of two clinicians and two pediatric radiologists, on a seven-point scale from "definite child abuse" to "definite unintentional injury." A middle rating of "unknown" was used if there was not enough information to reach a consensus. RESULTS: Of the 253 fractures in 215 children that were identified, we categorized 24.2% as abuse, 8.4% as unknown, and 67.4% as unintentional injuries. Fractures that were considered likely due to abuse were (1) fractures in children whose caretakers reported either a change in the child's behavior, but no accidental event, or a minor fall, but the injury was more severe than expected; (2) fractures of the radius/ulna, tibia/fibula, or femur in children less than 1 year of age; or (3) midshaft or metaphyseal fractures of the humerus. Linear fractures of the parietal bone were the most common skull fractures, whether due to abuse or unintentional injuries. CONCLUSION: In young children with fractures, child abuse is common. By comparing fractures due to abuse and those due to unintentional injuries, we obtained empiric evidence to help clinicians and radiologists correctly examine children with such serious injuries.

CT differentiation of benign and malignant lung nodules in children.

The superiority of computed tomography (CT) for detection of lung nodules has been documented and attempts have been made to distinguish benign from malignant lesions in adults. We attempted to characterize lung nodules in 12 children with solid malignant tumors (aged 8 months to 17 years) in an effort to differentiate benign from metastatic disease. All scans were performed at 10-mm contiguous intervals on a GE 9800 CT scanner. The scans were retrospectively viewed by two pediatric radiologists independently and without knowledge of the pathological findings. All biopsies were done via open thoracotomy. The CT findings were correlated with pathology results. Twelve children had 13 nodules biopsied. Six of these showed malignancy, two showed inflammatory changes, and two had a reactive subpleural lymph node. In three children, no abnormality was found and a biopsy was not obtained. One child had a metastatic nodule in one lung, and a simultaneous inflammatory nodule in the other. The radiologists agreed with each other on the CT interpretation in 11 of 13 surgically explored areas. They correctly predicted malignancy in four cases and correctly excluded it in two cases. However, they were simultaneously incorrect in five instances. Our conclusion is that, contrary to reports in adults, a tiny nodule may be either benign or malignant. Malignancy cannot be separated from benign disease by CT established criteria.

Outcome of nonoperative management of splenic injury with nuclear scanning. Clinical significance of persistent abnormalities.

Uncertainties remain about the frequency and need for diagnostic imaging following recovery from splenic injury with nonoperative management. To gain further understanding, the final appearance of the splenic roentgenographic image was evaluated in 20 consecutive children (mean age, 10.1 years) undergoing serial studies up to 70 weeks following injury. A total of 65 technetium 99m sulfur colloid scans, including 45 follow-up studies, were obtained and evaluated. By 20 weeks following injury, six patients (30%) were normal, four (20%) demonstrated minimal residual effects, and 10 (50%) had significantly improved, leaving some persistent abnormality. None of the patients in the last group showed any clinical problem. No distinctions could be made by comparing the severity of the initial injury with a persisting imaging defect. We conclude that clinical considerations alone should determine whether any follow-up imaging be performed in children recovering from splenic injury.

Long-bone fractures in young children: distinguishing accidental injuries from child abuse.

While testifying in child abuse cases, physicians have been frustrated by the lawyer who asks, "Doctor, how did this injury happen?" The medical records and radiographs of 215 children younger than the age of 3 with fractures evaluated by a pediatric service during a 5-year period were retrospectively reviewed in an attempt to elucidate the mechanism of childhood fractures. Based on these reviews, two clinicians and two pediatric radiologists rated the likelihood that the fracture was either accidental or due to child abuse. Long-bone fractures were strongly associated with abuse. This report focuses on the 39 children with either humeral or femoral fractures. Fourteen children had humerus fractures. Eleven were considered to be the result of child abuse, and 3 the result of accidents. The latter 3 were supracondylar elbow fractures in children who fell from a tricycle, a rocking horse, or downstairs. Humerus fractures other than supracondylar fractures were all found to be due to abuse. There were 25 femur fractures. Nine were found to be from abuse, 14 were found to be from accidents, and 2 could not be rated. Sixty percent of femur fractions in infants younger than 1 year of age were due to abuse. Although it is taught that femur fractures in young children are inflicted unless proven otherwise, in this study it was found that femur fractures often are accidental and that the femur can be fractured when the running child trips and falls.

Brain MR in patients with Langerhans cell histiocytosis: findings and enhancement with Gd-DTPA.

The brains of eight patient with Langerhans Cell Histiocytosis (LCH) were studied with magnetic Resonance Imaging (MRI). One scan was normal and a spectrum of abnormalities was seen in the others. Five patients had absence of the posterior pituitary bright spot, and four with evidence of pituitary dysfunction had a lesion in the region of the hypothalamus. An orbital extraconal mass was noted in one child with exopthalmus. This decreased in a follow-up study after Vinblastine therapy. The cerebellum was abnormal in two patients; the area of the dentate nuclei exhibited abnormal signal in one asymptomatic child and the MRI of another boy with a ten year history of progressive cerebellar dysfunction showed cerebral and cerebellar atrophy. Three of the five patients with deficiency of antidiuretic hormone (ADH) were studied both before and after the administration of intravenous Gadolinium-DTPA. In all three, after administration of the contrast agent, there was enhancement of involved areas.

Society of Uroradiology Award paper. The pars infravaginalis gubernaculi: importance in the identification of the undescended testis.

The gubernaculum, a cordlike structure that extends from the testis to the scrotum and guides the testis in its descent, has a bulbous termination, the pars infravaginalis gubernaculi. We reviewed seven surgically proved cases in which the pars infravaginalis gubernaculi was mistaken for an undescended testis on imaging studies. The studies included sonography (five cases), CT (two cases), and MR imaging (two cases). Identification of the mediastinum testis on sonograms or MR images confirms that a structure is testis and not the pars infravaginalis gubernaculi. In two of these patients, testicular venography was used to further identify the undescended testis. In these two patients, the pampiniform plexus, which is used to identify the presence and position of testis, was located adjacent to the pars infravaginalis gubernaculi. Our experience indicates that the pars infravaginalis gubernaculi can be similar in appearance to the undescended testis on any imaging study. The finding of an apparent cord leading to a testislike structure on caudad sectional imaging does not obviate searching for the testis as far as the renal hila.

Failure of development of the growing breast after radiation therapy.

Four cases are presented in which young girls received radiation therapy to treat childhood malignancies. Subsequently, one breast, which had been included in the radiation field in each case did not develop. This phenomenon has been seen after orthovoltage as well as supervoltage therapy, but is not mentioned in recent diagnostic imaging literature.