Richard G. Sheehan

Large cell lymphomas of the stomach: improved prognosis with complete resection of all intrinsic gastrointestinal disease.

Thirty-seven consecutive patients with large cell lymphoma involving the stomach were evaluated between 1974 and 1980. All seven stage IE patients underwent complete resection of the stomach and all patients are alive 21-41 mo after resection. Of 18 stage IIE, 11 underwent complete resection. Two resected patients without postoperative therapy died of their disease. Six patients treated with chemotherapy are alive and well, and two of three patients treated with radiotherapy remain alive without disease. Seven patients had incomplete resection or biopsy, and only one remains alive at 34 mo. Of eight stage IV patients, four had complete resection and chemotherapy without recurrence of their disease. All four patients who were not resected have died of their disease. This study strongly supports the role of early surgery in the management of gastric large cell lymphomas.

The Control of Iron Absorption by the Gastrointestinal Mucosal Cell

Gastrointestinal mucosal factors controlling rates of iron absorption were studied utilizing an in vivo closed duodenal loop technique. Cellular distribution of newly absorbed radioiron was identified by molecular sieve and iron-exchange chromatography of the mucosal cell supernate. In the normal animal, iron rapidly appeared in ferritin, and this fraction accounted for greater than 90% of mucosal supernatant radioactivity after 60 min absorption time. The nonferritin radioiron appeared to be unbound iron salts. In the presence of increased iron absorption induced by iron depletion or hemolysis, the major difference from the normal distribution pattern was an increase in the proportion and quantity of the free iron salts. Incorporation of newly absorbed iron into ferritin did not correlate with the rate of iron absorption. No evidence was found for a specific soluble iron-chelating molecule within the mucosal cell. The nonheme iron content of the mucosal supernates from iron-deficient and hemolyzing animals were significantly lower than in the normal animal.The data are consistent with hypotheses which suggest that iron absorption rates may be controlled in part by the rate of initial iron uptake by the mucosal cell and that a membrane transport mechanism exists which is modulated by the nonheme iron content of the mucosal cell or some portion thereof.

Treatment of Cutaneous Sclerosis and Aplastic Anemia with Antithymocyte Globulin

We administered antithymocyte globulin to a 52-year-old man with cutaneous sclerosis (scleroderma) and severe aplastic anemia for treatment of the aplastic lesion. The use of this therapy resulted not only in marrow recovery but also in resolution of the sclerosis. This observation indicates that T lymphocytes, their products, or both, are important factors in the pathogenesis of cutaneous sclerosis. Furthermore, the success of this treatment could play a role in future investigations involving the treatment of scleroderma and scleroderma-like conditions.

The impact of dose intensity of standard chemotherapy regimens in extensive stage small cell lung cancer

Oncologists often attenuate the doses of chemotherapy drugs in published standard regimens to avoid toxicity. The impact on survival of this practice in patients with extensive stage small cell lung cancer (SCLC) is uncertain. We have compared the outcome of 85 patients treated with a program of cyclophosphamide, doxorubicin, and vincristine to a group of 37 patients treated with conventional regimens of higher dose intensity. The two groups of patients were shown to be equivalent in terms of staging evaluation, response and survival criteria, and pretreatment prognostic factors. The latter was confirmed by applying a published prognostic algorithm. Complete response rates (38% vs 14%) were significantly better with the higher intensity regimens (p = .003). The median survival (39 vs 26 weeks), 1 year survival (32% vs 12%), and overall survival (p = .002) were superior with the full-dose intensity protocols. Myelotoxicity was also greater with the contemporary treatments. Cox proportional hazards analysis, correcting for pretreatment prognostic variables, confirmed the improved survival with conventional doses of therapy (p = .0055). These results support the concept that full-dose intensity chemotherapy provides survival benefit in patients with extensive stage SCLC.

The relative value of conventional staging procedures for developing prognostic models in extensive-stage small-cell lung cancer.

Published prognostic models for small-cell lung cancer (SCLC) have either combined limited- and extensive-stage patients or have not included standard anatomic staging information to assess the relative value of the knowledge of specific sites and number of sites of metastases in predicting survival in extensive-stage disease. We studied 136 extensive-stage patients in whom traditional staging procedures were performed and in whom other previously demonstrated significant pretreatment variables were determined. Using the Cox proportional hazards model, when all data were included, three variables were significant: performance status (PS) (P = .0001), number of sites of metastases (P = .0010), and age (P = .0029). A prognostic algorithm was developed using these variables, which divided the patients into three distinct groups. When the anatomic staging data were omitted, the serum albumin (P = .0313) was the only variable in addition to PS (P = .0001) and age (P = .0064) that was significant. An alternative algorithm using these three variables was nearly as predictive as the original. Therefore, in extensive-stage patients, reasonable pretreatment prognostic information can be obtained without using the number or specific sites of metastases as variables once the presence of distant metastases has been demonstrated.

Radionuclide imaging of bone marrow metastases with a Tc-99m labeled monoclonal antibody to small cell lung carcinoma

The detection of metastatic disease confined to the bone marrow compartment has in the past been technically limited. We have identified excellent imaging of bone marrow metastases during the evaluation of a Tc-99m labeled monoclonal antibody (NR-LU-10 Fab) (NeoRx Corp., Seattle, WA). This occurred during a study to assess the monoclonal antibodys ability to detect sites of small cell cancer (primary and metastatic). The study by design compares areas seen by the monoclonal antibody scan with those found by standard staging methods in patients with small cell lung cancer. Standard staging included chest x-rays, bone scans, CT studies of the abdomen, and histologic examination of the bone marrow. Fifteen patients have been evaluated, four on two occasions, for a total of 19 monoclonal imaging studies. Metastasis to the marrow compartment was identified by the monoclonal imaging in all patients whose bone marrow biopsies were positive for small cell carcinoma, and it was primarily responsible for the eventual detection of extensive disease (marrow involvement) in one patient. Thus it appears that compartmental bone marrow imaging for metastatic disease is possible with immunoscintigraphy.

Influence of Hemoglobin Phenotype on the Mean Erythrocyte Volume

The influence of the hemoglobin (Hgb) phenotype on mean erythrocyte volume was re-examined in the light of recent evidence indicating a poor correlation between manual and more precise automated methods of measurement. The present studies identified a 17.6% frequency of microcytosis in a population of nonanemic Black males, a value higher than previously appreciated. In addition, it was shown that the frequency of microcytosis was also a function of the Hgb phenotype. Thus, 9.4% of Hgb AA, 18.6% of AS and 26.5% of AC subjects had microcytic erythrocytes. The data presented are consistent with the hypothesis that both the alpha-gene complement and the beta-chain phenotype contribute to the erythrocytic mean corpuscular volume and that the frequency of microcytosis in a patient population is a function of both of these variables.

Double modulation of 5-fluorouracil in the treatment of advanced colorectal carcinoma: report of a trial with sequential methotrexate, intravenous (loading dose) folinic acid, 5-fluorouracil, and a literature review.

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FUs potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FUs cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.

Interrelationships of Iron and Cobalt Absorption: Mucosal Distribution of Cobalt During Absorption

Summary The carcass transfer and subcellular distribution of cobalt during the period of rapid absorption were studied in normal rats and animals with iron deficiency or phenylhydrazine induced hemolytic anemia. Although carcass transfer of cobalt was increased in the latter 2 groups, no binding to soluble cytoplasmic molecules was found. Since iron and cobalt appear to share a common absorptive mechanism, these findings support the proposition that soluble cytoplasmic molecules do not play a major role in the control of absorption of these cations.