Jose J. Terz

Analysis of the cell kinetics of human solid tumors

The cell cycles (tc) of seven human solid tumors (lung, maxillary antrum, malignant schwannoma, malignant melanoma, colon cancer, and two breast cancers) were studied in vivo following the pulse labelling with intravenous tritiated thymidine and multiple biopsies. The standard components of the cell cycle were observed by radioautography, and the duration of the tc was analyzed by the per cent of labelled mitosis curve, the grain halving method, and computer model (G. G. Steel) which allows the determination of the variants of each component of the cycle. The determined tc ranged from 14 hrs. (lung cancer) to 44 hrs. (schwannoma), and the DNA synthetic period ranged from 5.5 hrs. ((lung cancer) to 21 hrs. (melanoma). There was a significant discrepancy between the calculated tumor doubling time and the measured doubling time. The rate of cell loss calculated on the basis of this difference ranged between 11% (lung cancer) to 86% (melanoma). The growth fraction ranged between 25% (breast cancer) and 80% (lung cancer). No significant discrepancies were observed in the estimation of the cell cycle by the different methods. A second wave of labelled mitoses was always demonstrated if frequent samples were obtained. The analysis of our data, as well as the review of the reported cases, shows a wide variation in the duration of the cell cycle in different tumors. Therefore, no significant correlation can yet be established between the type of tumor and the kinetics of the cell components.

Postirradiation sarcoma (malignant fibrous histiocytoma) of axilla.

A case is reported of a patient who developed a histologically unusual sarcoma in the axilla and chest wall 8 years after receiving radiation therapy (6500 rad) for carcinoma of the breast. This sarcoma showed light, and electron‐microscopic features of a malignant fibrous histiocytoma, a tumor not documented among 24 previously reported cases of postirradiation sarcoma following the diagnosis of breast carcinoma. In addition, the literature is reviewed and discussed regarding postirradiation sarcoma in general following breast carcinoma.

Medical and surgical adrenalectomy in patients with advanced breast carcinoma

Twenty‐four postmenopausal patients with metastatic breast carcinoma were placed on aminoglutethimide and dexamethasone as a form of reversible medical adrenalectomy. Six patients experienced adverse side‐effects. Of the 18 remaining patients 50% had a definite subjective or objective response to therapy. Thirteen of these patients underwent subsequent surgical adrenalectomy after a maximum of 3 months trial of the medical regimen. In every patient the response to therapy was identical with the two modalities of therapy. In those postmenopausal patients with metastatic breast cancer who are felt to have a hormone‐ dependent tumor by clinical and/or hormonal assay criteria, medical adrenalectomy may eventually be a feasible replacement for surgery in selected cases. As important, perhaps, is the potential value of this medical adrenalectomy as a reliable indicator of the subsequent response to endocrine ablative therapy.

Neoplasms of the small intestine

Our experience with small intestinal neoplasms at the Medical College of Virginia has been reviewed. There were 78 benign and malignant neoplasms observed in our surgical pathology laboratory over a 20-year period. There were 34 benign small-bowel tumors, but the majority of these lesions were asymptomatic incidental findings at the time of surgery for other conditions. There were 21 patients with malignant neoplasms of the small bowel and 23 patients with carcinoid, a potentially malignant lesion. Clinical observations and the results of treatment are reviewed.

Analysis of the cycling and noncycling cell population of human solid tumors.

The size and kinetics of the cell population of six advanced human solid tumors were analyzed following the continuous infusion of H3‐TDR for a period of 6 to 21 days. By using the labelling indices of the cells in interphase and mitosis, and the rate of label incorporation, it was found the only 10 to 40% of the tumor cell population was replicating at any given time. Fifty‐five percent to 85% of the remaining cell mass eventually entered into cycle at least once. Anywhere from 5% to 40% of the cell population remained arrested in G2 or G0 in individual cases during the period of observation. The significant size of the “resting” cell compartment is undoubtedly one explanation for the relative insensitivity of advanced adult solid tumors to current cell cycle‐oriented therapeutic regimens.

Preoperative irradiation for head and neck cancer: A prospective study

A prospective clinical trial of preoperative irradiation for Stage II, III, and IV squamous carcinoma of the head and neck was initiated at the Medical College of Virginia in January, 1969. In patients receiving preoperative therapy, treatment was calculated to give a midline total dose of 1,400 rads in two equal fractions delivered 24 and 48 hours prior to the surgical procedure for oral cavity, oropharyngeal, or pharyngeal cancer. The surgical procedure in all instances consisted of wide resection of the primary lesion in continuity with unilateral or bilateral neck dissection. By December 31, 1972 there were 143 patients entered into this study with followup periods ranging from 6 to 54 months. The morbidity, mortality, and survival characteristics of the preoperative irradiation and “surgery only” groups are essentially the same. No significant difference in local recurrence rate has been observed between the two groups. Although the different anatomical sites cannot be individually examined at this time, it is considered that no major change in clinical course will result from this type and dosage of preoperative irradiation to Stages II, III, and IV squamous carcinoma of the oral cavity, oropharynx, and pharynx.

Experience with opposite breast biopsy in patients with operable breast cancer.

One hundred and nine patients with unilateral breast carcinoma and no palpable abnormality of the contralateral breast were evaluated by opposite breast biopsy. Our patient population yielded four noninfiltrating carcinomas, and one infiltrating carcinoma for an incidence of 4.5%. The one infiltrating cancer was suspected on a preoperative mammogram. We have discontinued the routine use of the opposite breast biopsy as a diagnostic tool in patients with unilateral breast cancer, in patients with no palpable abnormality and a normal mammogram.

Primary reconstruction of the mandible with a wire mesh prosthesis

A stainless steel wire mesh prosthesis was used as a primary mandibular replacement in 102 patients following resection of malignant neoplasms arising in the head and neck. In 67 patients the prosthesis was considered successful. Failure of the host to tolerate the prostheses was associated with history of previous irradiation, extensive resections, and the loss of distant skin flaps used for coverage of the prosthesis. But the prosthesis is tolerated by the host in 90% of the cases if it is inserted in a non-irradiated bed, covered with local tissues, and the resection is limited to the maxillo-oral complex only.

Primary oropharyngeal cancer and hypercalcemia

Hypercalcemia was found in five patients with primary squamous cancer arising in the oropharynx with no clinical and radiologic evidence of distant metastases. In two patients the serum calcium levels returned to normal following removal of the primary tumor. In three patients the determination of the urinary 3′5′ cyclic adenosine monophosphate and the quantitative microradiographic study of bone biopsies strongly suggested the presence of abnormal levels of PTH.

Medical adrenalectomy in patients with advanced breast cancer

Medical adrenalectomy, consisting of aminoglutethimide plus either dexamethasone or hydrocortisone, was administered to 53 women with advanced breast cancer. Sixteen (30%) patients had an objective response, five patients had stabilization of disease, 26 patients demonstrated progression of disease, two patients did not adhere to protocol, and four patients had severe toxicity necessitating discontinuation of the drugs. Medical adrenalectomy accurately predicted response to subsequent surgical adrenalectomy in 23 patients. Estrogen receptor (ER) data accurately predicted response (eight of nine (89%) ER‐positive patients responded) or failure (only two of 14 (14%) ER‐negative patients responded) to medical adrenalectomy. Thirty (of 51 women adhering to protocol) had no toxicity. Therefore, it appears that medical adrenalectomy is safe, usually well tolerated, and can accurately predict response to surgical adrenalectomy. Its use should be limited to ER‐positive patients, and it may totally supplant surgical adrenalectomy in the management of advanced breast cancer.