Faculty Bibliography

Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.

Radical therapy for locally advanced or recurrent gynecologic malignancies (LARGM) may include interstitial brachytherapy (IB) when intracavitary brachytherapy is impossible or inadequate and external beam teletherapy would be limited by surrounding normal tissue tolerance. Sixteen women received IB as all or part of their treatment at North Shore University Hospital for the treatment of locally advanced primary or recurrent tumors of gynecologic origin from May 1988 through September 1990. Primary sites included the vulva (3), vagina (2), cervix (7), and endometrium (4). Radiosensitizing chemotherapy was used in 8 patients. With a median follow-up of 23 months (range, 12-44 months), 11 patients (69%) have experienced continuous local control of their tumor and 4 patients (25%) have experienced severe complications. While significant risks may attend the use of IB, IB is an integral part of management for select patients with LARGM

The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed.

RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms

Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas

Between 1972 and 1988, 25 patients were treated by radiation therapy (RT) alone for pituitary macroadenomas causing visual impairment. Twenty-three patients were evaluated by a neuro-ophthalmologist before treatment and at the time of follow-up review. Radiation treatment consisted of 4000 to 5000 cGy over 4 to 5 weeks. The median follow-up period was 36 months (range 2 to 192 months). Eighteen patients (78%) experienced visual field improvement. Deterioration occurred in four patients due to tumor recurrence, tumor hemorrhage, possible optic nerve necrosis, and optic chiasm herniation. Visual field improvement occurred predominantly in patients whose pretreatment visual field defects were less than a dense hemianopsia, who did not have diffuse optic atrophy, and who were younger than the median age of 69 years (p less than 0.001). Visual acuity improvement occurred in patients without diffuse optic atrophy, with only mild impairment of the visual acuity, and with only mild visual field loss prior to RT (p less than 0.002). It is concluded that there is a subset of patients with pituitary macroadenomas and visual impairment for whom primary RT is a treatment option

The management of patients with pituitary adenomas by radiotherapy alone, using modern techniques of evaluation and current standards of treatment, has not been examined. This is a retrospective review of 29 such patients with nonfunctional or prolactin secreting pituitary macroadenomas. Patients were analyzed by visual fields, hormone levels, and CT scans. All but one patient received a tumor dose of 4500 cGy in 4 to 5 weeks. The tumor was controlled in 26 of 28 (93%) patients for an observed period of 3 to 14 years. Seventeen of 21 (81%) patients with visual impairment experienced normalization or improvement, and seven of ten (70%) patients with hyperprolactinemia achieved normalization of their serum prolactin levels. Post-treatment CT scanning revealed persistent tumor in nine of 17 patients despite clinical improvement. We conclude that: (a) radiotherapy is an effective treatment for these tumors; (b) doses need not exceed 4500 cGy in 25 fractions; (c) radiation is effective for improving vision; (d) radiation can normalize hyperprolactinemia; and (e) tumor regression is variable and unrelated to observed symptom regression