Search

Fine-needle aspiration biopsy for cytologic diagnosis was performed on seven patients suspected of having pancreatic tumors. A 23-gauge biopsy needle was accurately placed in the suspicious lesion under ultrasonic guidance. Six patients had tumors; of these, five had a definite cytologic diagnosis, and the sixth was suspicious of tumor. There was no morbidity associated with the procedure in these patients. Although fine-needle biopsy is not expected to prolong life in patients with pancreatic tumors, it does eliminate the need for more complicated, expensive, uncomfortable and hazardous diagnostic procedures. In many cases exploratory surgery may be obviated.

Serial carcinoembryonic antigen (CEA) titers were measured in 38 patients receiving chemotherapy for metastatic carcinoma of the colon, pancreas, and stomach. CEA levels were initially elevated (over 2.5 ng/ml) in 26 patients (12/20 colonic, 8/10 pancreatic, 6/8 gastric). Seventeen patients had rising serial CEA values during therapy; 13 had evidence of tumor progression, 3 had stable disease, and 1 had no measurable disease. Nineteen patients had stable CEA levels which were either persistently elevated (11 patients) or normal (8 patients). Ten of 11 patients with elevated CEA levels developed tumor progression. In 8 patients with consistently normal CEA levels, 6 (colon) had no evidence of progressive tumor, and 2 (1 pancreatic and 1 gastric) eventually died of metastatic disease. CEA levels decreased in 2 patients with colon carcinoma during remission from chemotherapy. A rising CEA titer often presages clinical deterioration, although elevated CEA levels may remain stable despite progressive disease. Persistently normal CEA, however, is a favorable prognostic sign. The limited effectiveness of chemotherapy for gastrointestinal cancer in this series precludes any definitive conclusion regarding the effect of chemother-apeutically induced tumor regression on CEA levels, although there is suggestive evidence that CEA correlates with remission.

A 2-drug combination chemotherapy regimen of 5-fluorouracil (FU) and cytosine arabinoside (ara-C) was used in 23 patients with gastrointestinal cancer. The drugs were administered as a mixture by daily continuous infusion for 5 days at 4-wk intervals. Dosages for each drug were: FU, 1.1 gm/m2/day and ara-C, 50 mg/m2/day. The incidence of leukopenia (WBC, less than 3,500/mm3) was 36% and of thrombocytopenia (platelets, less than 125,000/mm3), 18% during 33 courses administered at full doses. No clinical antitumor effects were observed in 18 patients evaluable for therapeutic response. The addition of ara-C to a nonmyelosuppressive dose schedule of FU results in potentiated marrow suppression, and the antitumor effect for the combination is less than would have been predicted for either drug alone.

MCCNU and cyclophosphamide are synergistic in animal tumor systems and have different chronology patterns for dose-limiting myelosuppression. The combination was employed in 49 patients with metastatic cancer with each drug administered on successive days and repeated at 6-week intervals. A total of 108 courses of therapy were monitored, and leukopenia (WBC less than 3,000 cells/mm3) and thrombocytopenia (platelets less than 150,000/mm3) were observed in 47 and 30%, respectively, at nadir days 15 and 22. No clinically beneficial effects were observed in 40 patients with measurable disease. Combination chemotherapy employing nitrosoureas have not, as in this study, generally demonstrated synergistic therapeutic effects possibly related to the low level of antitumor activity of nitrosoureas in solid tumors and the use of suboptimal doses for one of more agents in the combination.

Methyl CCNU and Adriamycin have dissimilar patterns of myelosuppression and different mechanisms of antitumor activity. A clinical trial of the combination was undertaken on this basis. Methyl CCNU (150–200 mg/m2) and Adriamycin (40–90 mg/m2) were administered at 5–6-week intervals. Thirty-one patients (26 with breast cancer) were treated. Toxicity patterns were comparable to previous reports for the two agents. Myelosuppression was common (leukopenia 13/16; thrombocytopenia 10/16) but unassociated with complications. The leukopenic and thrombocytopenic nadirs occurred at 2 weeks and were consistent with that observed for Adriamycin, with a delayed recovery (5–6 weeks) related to the nitrosourea. Cumulative marrow suppression was suggested by the earlier nadirs with successive courses of therapy. Five objective responses occurred (CR 2, PR 3) and stabilization of disease was achieved in an additional 5 patients. The low level of activity of nitrosoureas in breast cancer and the extensive prior treatment may account for the low response rate to this combination.

Eight-four patients with renal cell carcinoma were analyzed retrospectively in order to 1) determine the effectiveness of systemic chemotherapy—hormonal and non-hormonal, 2) identify the clinical features of renal cell carcinoma that may be important in prognosis and 3) characterize the paraneoplastic features of renal cell carcinoma. Metastatic disease was present at diagnosis in 57 per cent of the cases and developed within 1 year in an additional 19 per cent. Multiple sites of metastasis were paradoxically associated with a longer survival (20 months median) compared to single-organ metastasis (5 to 11 months median). Paraneoplastic syndromes occurred in up to 40 per cent of patients with variable survival. Metastatic disease was unresponsive objectively to either primary nephrectomy or to a variety of chemotherapy trials.

Erythrocytosis associated with the presence of a hemoglobin with increased oxygen affinity has been reported for 10 hemoglobin variants, most of which demonstrate altered electrophoretic mobility. Several members of a family were found to have erythrocytosis, and both the whole blood and the hemoglobin exhibited increased oxygen affinity. Phosphate-free hemoglobin solutions had a normal Bohr effect and reactivity to 2,3-diphosphoglycerate. The electrophoretic properties of the hemoglobin were normal, but on peptide mapping of a tryptic digest of the isolated beta-chains, a normal betaT11 peptide and an abnormal betaT11 with greater R(f) were seen. Analysis of the abnormal peptide showed the substitution of leucine for the normal proline at beta100 (helical residue G2).The hemoglobin variant, designated Hb Brigham, serves to emphasize the necessity for detailed evaluation of the structure and function of hemoglobin in familial erythrocytosis even with electrophoretically "normal" hemoglobin.

The effect of mantle irradiation therapy for Hodgkin's disease on physiologic indices of pulmonary function including lung volume, flow rates, and diffusing capacity was monitored serially in 11 patients. Lung volumes including total lung capacity (TLC) and inspiratory capacity (IC) were maximally affected at nine months but returned toward normal by 24 months. Diffusing capacity was reduced prior to radiotherapy and decreased further following treatment in more than 50% of patients. Patients with intrathoracic Hodgkin's disease had lower initial pulmonary indices which improved with tumor resolution on radiotherapy, and patients without intrathoracic disease had a comparatively greater decrease in pulmonary function following irradiation, but this was transient and recoverable.

47 patients with Hodgkin’s disease presenting after age 60 were analyzed retrospectively for clinical presentation, distribution of disease, and histopathology, and compared to a younger control group. The types of clinical presentation included: local or generalized adenopathy, 50%; ‘B’ symptoms, 25%; ‘unusual manifestations’ and intra-abdominal complications, 13%; and incidentally discovered disease, 12%. In contrast, the younger group presented less often for symptoms (p

Five patients with breast cancer and malignant melanoma are reported. Two patients had a third primary malignancy. In 4 out of 5 patients the breast tumor was the initial tumor discovered, and in 4 out of 5 the second tumor evolved metachronously. No specific carcinogenic factor could be established. The low malignancy potential of the melanoma by pathologic criteria may explain the lack of previous reports of this association.

19 patients with metastatic gastrointestinal malignancy were treated with a regimen of 5-fluorouracil (FU) 500 mg/m2 intravenously and hydroxyurea (HU) 80 MG/KG orally administered on consecutive days weekly. Antitumor responses were not observed and an unusually high incidence of neurotoxicity (21%) was noted related to dose. It is suggested that the lack of therapeutic effect and the observed toxicity may be related to the biochemical interaction of FU and HU resulting in an inability to convert FU to the active metabolite and an accumulation of catabolic products with neurotoxic effects.

Procarbazine is a methylhydrazine derivative used in the treatment of Hodgkin's disease. Two patients who developed allergic hypersensitivity reactions, one with near-fatal allergic pneumonitis and one with allergic dermititis are described. A mechanism of sensitization is suggested, and the importance of awareness of this reaction and the need for early lung biopsy are stressed.

Methotrexate and bleomycin are both active in epidermoid tumors. They have different mechanisms of action and different host effects particularly with regard to myelosuppression. The concurrent administration of methotrexate and bleomycin was used in 30 patients with metastatic tumors, primarily epidermoid in type. Ten of 19 patients evaluable for therapeutic response demonstrated objective tumor regression (2 complete and 8 partial) with a median duration of response of 4 months. Bleomycin-induced pulmonary toxicity occurred in 14% with 1 mortality (25%). Marrow suppression developed in 50% of evaluable patients (10 of 21 WBC

In Reply.— Dr. Davidson's comments are appropriate in that judicious venography can be performed safely in most patients. However, the major issue is whether venography contributes substantially to the diagnosis and potential treatment. Our position is that the diagnosis of SVCS is a clinical one, and that treatment is not determined in most circumstances by the venogram. Furthermore, the potential complication, which is primarily hemorrhage from the venapuncture site, though of a low order of incidence, does not justify routine venography. Dr. Johnston's comments with regard to a controlled trial of radiation therapy do not seem appropriate. Clearly, radiation therapy is an effective palliative measure in the majority of patients with SVCS, whether or not one demonstrates relief of venous obstruction objectively. Additional measures, such as fluid restriction and diuretic therapy, could and should be employed. However, these measures are clearly not focusing on the specific pathophysiology of the syndrome.

† Superior vena cava syndrome (SVCS) is an acute or subacute oncologic emergency with typical clinical features. The syndrome is almost invariably secondary to a malignant process. The treatment of choice is irradiation, but in resistant cases or in those instances in which radiation tolerance is achieved, either surgery or chemotherapy, or both, may play a crucial role. The major pitfalls in management relate to attempts to establish the site of obstruction and to obtain specific tissue diagnosis. ( JAMA 231:58-61, 1975)

Central nervous system (CNS) metastases are a common clinical problem, and management spans the three major therapeutic disciplines in oncology. Surgery, radiotherapy, and chemotherapy are employed alone, in combination, or sequentially and are based on four local factors—the number, size, site, and depth of the lesions; and three tumor factors—the natural or biologic history of the primary tumor, the quantitative host tumor burden, and the tumor responsiveness to individual therapeutic modalities. The median survival of patients with CNS metastasis is 3 to 12 months and is not necessarily compromised by the CNS lesions, if the diagnosis is established and therapy promptly instituted. (JAMA234:748-751, 1975)

Nephrotic syndrome in association with Hodgkin disease may be caused by the deposition of immune complexes within the kidney. A patient with Hodgkin disease is reported in whom the nephrotic syndrome developed. Immunoglobulin deposits and electron-dense accumulations were demonstrated in the glomerular basement membranes. A clinical remission was achieved with therapy that was specifically directed at the Hodgkin disease. The hypothesis is proposed that Hodgkin disease tumor-specific antigens may compose a portion of the deposited immune complexes.

The accumulation of fluid in the potential space between serosal membranes may develop in 5% to 50% of patients with disseminated malignant disease.1Malignant pericardial effusion is particularly important because of its insidious clinical expression and the life-threatening potential of cardiac tamponade. Two mechanisms for the production of pericardial effusion that have been suggested are (1) tumor implantation on serosal surfaces leading to exudation of fluid, and (2) obstruction to lymphatic flow by mediastinal or hilar neoplastic infiltration causing transudation of fluid within the pericardial sac.2In the experimental model, lymph flow proceeds from the endocardial to the epicardial surface, and pericardial effusion is an accumulation of fluid exuding from the visceral pericardium (epicardium). Mere obstruction of the mediastinal lymphatic system draining the heart is inadequate to produce pericardial effusion, and additional ligation of the coronary sinus and the anterior coronary veins is essential. These studies have two