Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1) Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se: and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 postmenopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] was determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin]) was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not differ significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition (pre-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin].

We studied 43 patients with metastases to the base of the skull to determine whether clinical symptoms localized the lesions accurately. We identified five clinical syndromes: orbital, parasellar, middle fossa, jugular foramen, and occipital condyle. The orbital and parasellar syndromes were characterized by frontal headache, diplopia, and first-division trigeminal sensory loss. Proptosis occurred with the orbital but not the parasellar syndrome. The middle-fossa syndrome was characterized by facial pain or numbness. The jugular foramen syndrome was characterized by hoarseness and dysphagia, with paralysis of the ninth through eleventh cranial nerves. The occipital condyle syndrome was characterized by unilateral occipital pain and unilateral tongue paralysis.

A series of 54 patients with spinal chordomas were treated at Memorial Sloan-Kettering Cancer Center between 1949 and 1976. Thirty-six lesions were located in the sacrococcygeal region and 18 involved the vertebral column at a higher level. The male to female ratio was 35:19. Vertebral chordomas generally occurred in a younger age group. Our radiological findings suggest that there is marked soft-tissue extension anterior to the vertebral column at the time of initial diagnosis. Eleven of 18 vertebral chordomas and 10 of 36 sacral chordomas were found to have disseminated metastases during their course. Analysis of the various modes of therapy reveals that the median survival for both groups is approximately 6 years. However, the 5-year survival for the sacrococcygeal group was 66% as opposed to 50% for the vertebral group. Radiation therapy produced significant palliation but objective evidence of tumor regression was difficult to assess. Chemotherapy in a small number of patients did not have any effect on the tumor. With the advent of computerized tomography scanning, further studies should be done to document the response of this tumor to radiation therapy.

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One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.

An analysis of 125 patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor treated at our hospital from 1934 to 1975 is presented. Cryptorchidism was corrected ipsilaterally or contralaterally in 83 patients with intrascrotal testis cancer when they were from 4 to 42 years old, either spontaneously (21 patients), by orchiopexy (51 patients) or by hormonal therapy (11 patients). Forty-two cryptorchid patients (uncorrected cases) presented with either ipsilateral inguinal (24 patients), abdominal (14 patients) or contralateral intrascrotal tumors (4 patients). Tumor histologic types on orchiectomy were pure seminoma in 54 patients, embryonal carcinoma in 35, teratocarcinoma in 33 and pure choriocarcinoma in 3. The 5-year survival rates were 60 per cent for the corrected cases and 63 per cent for the uncorrected cases according to cryptorchid state, and they were 78 per cent in patients with pure seminoma and 48 per cent in patients with other germinomas according to histologic type. The majority (58 of 73) of 5-year survivors received regional lymphatic irradiation, in 39 patients with pure seminoma, and/or systemic chemotherapy, in 19 patients with germinal carcinomas, with or without regional lymphadenectomy.

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