Edwin C. Douglass

Chromosome Translocation in Peripheral Neuroepithelioma

PERIPHERAL neuroepithelioma (peripheral neuroblastoma) is an uncommon malignant tumor of the peripheral nervous system with a histologic appearance similar to that of classical childhood neuroblast...

Cytogenetic studies in ovarian cancer

Cytogenetic studies of ovarian cancer have been conducted in the Medicine Branch, NCI, National Institutes of Health for 5 years. A total of 72 patients were studied by direct preparation and/or 1- to 3-day short-term culture of ascites (86 samples), pleural fluid (4 samples), and tumor (2 samples). Repeat examinations (1-24 months later) were performed in 7 of the 72 patients. Forty-four patients (62%) were successfully analyzed with banding techniques: 6 patients had adenocarcinoma, 7 had serous adenocarcinoma, 13 had serous papillary adenocarcinoma, 7 had serous papillary cystadenocarcinoma, 2 had mucinous adenocarcinoma, 6 had undifferentiated or poorly differentiated adenocarcinoma, 1 had clear cell adenocarcinoma, and 2 were not classified. Of these 44 patients, 29 had received prior chemotherapy, 14 were untreated, and in 1 patient the treatment status was unknown. Aneuploidy was observed in all patients and there was considerable variation in the chromosome numbers (even within single samples), often ranging from diploidy to triploidy to tetraploidy. All 44 patients had numerical abnormalities and 39 had structural abnormalities. The chromosomes most frequently involved in structural abnormalities (in decreasing order according to the number of patients involved) were #1, #3, #2, #4, #9, #10, #15, #19, #6, and #11; the least involved chromosomes were #21 and #5. Clone formation and the number of chromosomes involved in structural abnormalities increased with duration of disease and were more extensive in patients treated with chemotherapy than in patients treated with surgery alone. Our data did not show a deletion of chromosome #6 (6q-) to be specific for ovarian cancer.

Predominance of Pilocytic Histology in Dorsally Exophytic Brain Stem Tumors

We report the magnetic resonance imaging (MRI) and clinico-histologic characterization of dorsally exophytic brain stem gliomas (DEBSGs). Between 1983 and 1991, 12 of 51 patients evaluated for the diagnosis of brain stem glioma were found to have DEBSGs emanating from the pons, pontomedullary junction or medulla. Eleven of the 12 patients had classic juvenile pilocytic astrocytomas. Unlike most other brain stem tumors, these patients were young (median 38 months, range 17-75), had a relatively long duration of symptoms (median 7 months, range 2-24) and displayed signs of increased intracranial pressure with limited cranial nerve paresis, absence of pyramidal tract findings, and near normal brain stem auditory-evoked potentials. MRI characteristically showed sharply demarcated lesions with decreased signal intensity on T1, and increased intensity on T2 sequences. Except for cystic areas, these tumors showed bright, uniform enhancement after gadolinium-DTPA. In all patients, 50-100% of the tumor volume could be resected. Three of 10 patients who received no immediate postoperative treatment eventually demonstrated disease progression, and 2 patients with subtotal resections who were treated with radiation and/or chemotherapy postoperatively remain disease-free for extended periods of time. The only death occurred in the 1 patient treated with chemotherapy who died of secondary leukemia. The overall and progression-free survival of these patients at 2 years is 100 and 67% as compared to 18 and 21%, respectively, for other concomitantly treated nonexophytic brain stem gliomas.2+ the ability to achieve significant degrees of resection.

Solid alveolar rhabdomyosarcomas with the t(2;13). Report of two cases with diagnostic implications

Two patients having rhabdomyosarcomas with the recently described “solid variant” pattern of alveolar rhabdomyosarcoma are reported. Both tumors had aggressive cytologic features with monotonous sheets of round nuclei, but without fibrous septa, and both had been initially classified as embryonal rhabdomyosarcomas. Cytogenetic analyses of tumor explants from both cases revealed the t(2;13) chromosomal aberration typical of alveolar rhabdomyosarcoma. Both patients died of metastases, despite aggressive surgical and adjuvant therapy. This report represents the first karyotypic analyses of solid alveolar rhabdomyosarcomas and supports the inclusion of these tumors in the alveolar category despite the lack of fibrous septa.

Fractures in children treated with radiotherapy for soft tissue sarcoma.

There is a clear association between multimodal therapy for bone tumors and the development of skeletal complications; however, this has not been addressed in children with soft tissue sarcomas. We reviewed records of the 70 children treated for soft tissue sarcoma of the lower extremity at St. Jude Childrens Research Hospital between 1962 and 1991. Of the 12 patients who received radiation after surgical excision of their tumors, three subsequently developed fractures. Two of the three had also received chemotherapy. Our findings indicate that, although the risk of fracture after therapy for soft tissue sarcoma may be multifactorial, radiation may play a significant role. Minimizing the size of surgical incisions, improving radiotherapy techniques, maximizing chemotherapy, and emphasizing physical therapy and appropriate follow up can all serve to decrease long-term toxicities. Such optimal use of therapy could subsequently reduce side effects, such as osteoporosis and muscle and bone atrophy, that predispose patients to fractures.

Phase II study of 5‐fluorouracil/leucovorin for pediatric patients with malignant solid tumors

Background. 5‐Fluorouracil (5‐FU) activity for various carcinomas of adults has been enhanced through the synergistic effect of leucovorin. Few pediatric studies of 5‐FU in pediatric patients have been previously reported.

Phase I study of flavone acetic acid (NSC 347512, LM975) in patients with pediatric malignant solid tumors

To evaluate the anticancer agent flavone acetic acid (FAA). we conducted a Phase I trial involving 17 pediatric patients with various malignant solid tumors. Dosages investigated included 5.120 and 6,144 mg/m2 given as 3-hour intravenous infusions: and 10.000. 12.500. 15.000. and 17.500 mg/m2 delivered in a 24-hour constant infusion with alkalinization. Grade 2 or worse toxicity was minimal, with 2 patients having nausea/vomiting, 2 having diarrhea. 1 becoming hypertensive, 1 becoming hypertensive, and 2 having myalgia. Three patients who received a 17.500 mg/m2 dose had no toxicity. Disease was stabilized for a brief period in 2 patients—1 with brain stem glioma and 1 with astrocytoma. The FAA pharmacokinetics varied with an average (SD) terminal half-life of 27.9 hr (18.7), clearance of 2.041/hr/m2 (0.37), and steadystate volume of 19.9 L/m2 (10.6). This study was discontinued because FAA caused no significant toxicity or therapeutic responses at doses 2.5 gm/m2 greater than had been tolerated by adults.

Involvement of chromosome No. 22 in neuroblastoma

Abstract Cytogenetic studies on neuroblastoma tissue from a 17-year-old girl showed a single karyotypic abnormality, del(22)(q13). The relationship of this abnormality to previously described abnormalities in neuroblastoma and to other malignancies is discussed.