Eugene P. Frenkel

Cis‐platinum vestibular toxicity

Cis‐diamminedichloroplatinum has been proven to be an effective neoplastic agent. Nephrotoxicity and ototoxicity are two prominent side effects of this drug. Investigation of ototoxicity has been limited to auditory function. This report details the first known case of vestibular toxicity following platinum therapy. In addition, a prospective vestibular testing program is reported. Cancer 47:857–8589, 1981.

Use of enhanced computerized tomography to evaluate osmotic blood-brain barrier disruption.

Enhanced computerized tomography (CT) is a noninvasive means of monitoring blood-brain barrier (BBB) disruption. In the present study this technique was used to monitor the degree, distribution, extent, and reversibility of osmotic BBB disruption. With a canine model, the timing of administration of iodinated contrast agent was shown to be crucial to optimize enhancement by CT of the disrupted BBB. Meglumine iothalamate given intravenously resulted in excellent enhancement on CT scan. Intracarotid infusion of this contrast agent was less satisfactory. Under similar conditions, enhancement due to metrizamide was less marked and more transient than that observed with meglumine iothalamate. Systemically administered methotrexate after osmotic BBB disruption resulted in increased brain levels in areas that closely correlated with CT scan enhancement. These results suggest that the CT scan provides an excellent noninvasive monitor of both BBB disruption and the delivery of chemotherapeutic agents to the brain. (Neurosurgery 6: 49--56, 1980)

Cis-platinum induction chemotherapy in the multi-modality initial treatment of advanced stage IV carcinoma of the head and neck

Twenty‐eight previously untreated patients with unresectable and radical radiotherapy incurable advanced stage IV squamous cell carcinoma of the head and neck underwent cis‐diamminedichloroplatinum (DDP) induction chemotherapy followed by radiation with 6500 rad to the primary and 5000 rad to the supraclavicular area given over six weeks. Of the 26 patients completing this regimen, none had a complete remission after DDP alone. Following radiation therapy, 39% of the patients had a total regression of all disease. This modality converted 16 patients to operable candidates. After surgery, 68% of the patients were in complete remission. Survival was significantly correlated (P ≤ 0.001) with complete disappearance of disease, and surgical intervention was additive to chemotherapy and radiation. Histopathologic staging demonstrated that clinical assessment of residual disease in the neck determined after chemotherapy and radiation of the neck was unreliable. Therefore, radical neck dissection appears indicated in lesions initially staged as N2 and N3 irrespective of the postradiation clinical status of the neck region. Finally, a serious limitation of improved survival duration was the occurrence of disseminated disease in patients whose primary and regional lesions were well controlled.

The diagnostic dilemma of the “small round cell neoplasm”: Catecholamine fluorescence and tissue culture morphology as markers for neuroblastoma

Small round cell neoplasms, which include neuroblastoma, Ewings sarcoma, embryonal rhabdomy‐osarcoma, oat cell carcinoma, and lymphoma, are often confused with one another histologically. The advent of successful but distinct therapeutic approaches for different neoplasms has increased the need for precise diagnosis. The use of techniques ancillary to routine histologic or ultrastructural analysis allows better definition of the specific tumor type. Four cases of small cell tumor are described in which the initial working diagnosis was incorrect. The application of two diagnostic procedures for neuroblastoma was of great value in clarifying the proper diagnosis. These tests were a rapid fluorescence assay for intracellular catecholamines and a tissue culture assay for neurite outgrowth. Both of these methods are highly sensitive for neuroblastoma and distinguish neuroblastoma from other small round cell neoplasms. Their use confirmed this unsuspected diagnosis in three cases and excluded neuroblastoma in the fourth case.

Suprasellar germinomas (ectopic pinealomas): Aspects of immunological characterization and successful chemotherapeutic responses in recurrent disease

Two patients with suprasellar germinomas were initially treated successfully with radiotherapy, but subsequently they developed recurrent tumor 2 1/2 and 12 years later. The recurrent tumor was solely extraneural in the first patient because of seeding from a ventriculoperitoneal shunt, and in the second patient the tumor recurred as its initial site as well as in the 4th ventricle. Both tumors secreted the beta-subunit of human chorionic gondadotropin. A dramatic tumor response was seen in both patients with systemic chemotherapy consisting of a combination of cis-platinum, bleomycin, and vinblastine. The small cells in one of the suprasellar germinomas were shown to be predominately T lymphocytes on the basis of an examination of the cell surface markers on these cells. (Neurosurgery, 7: 352-358, 1980).

Diamond-Blackfan Syndrome in Adult Patients

Two adults with pure red cell aplasia are described. No extrinsic etiologic mechanisms were identified. Evidence of anemia was long-standing and varied in severity. Musculoskeletal abnormalities (webbed neck, Sprengels and Klippel-Feil deformities, and hand abnormalities) were similar to those seen in the congenital form of red cell aplasia (Diamond-Blackfan syndrome). As in the congenital variety, adrenal cortical steroids resulted in hematologic repair. These observations suggest that congenital (Diamond-Blackfan) pure red cell aplasia may be first recognized in adulthood and that steroids provide a potential therapeutic modality.

The Challenge of the Blood-Brain Barrier

Contemporary understanding of the blood-brain barrier (BBB) has been highlighted by Davson,5 Rapoport,50 and Bradbury3; their reviews have provided the critical basis for understanding the physiologic and pathophysiologic functioning of the BBB as it relates to clinical medicine. Human diseases and experiments of nature have helped illustrate the functioning of the BBB. This chapter presents examples in illustrative case reports.