Basal plasma glucagon levels of man.

The isolated perfused rat liver can serve as a bioassay system for glucagon, capable of detecting 10 mmug of this agent. Seven 15-ml plasma specimens obtained from different healthy volunteers after an overnight fast were assayed in this system; glucagon could not be detected in any of them, indicating concentrations significantly below 0.67 mmug per ml in all subjects. The effects of administering small doses of glucagon to patients were consistent with these results; imposition of increments to plasma glucagon concentration below 1 mmug per ml induced distinct and sustained increases in blood glucose. Observations of the biologic effects of glucagon, together with data on the rate of its inactivation by the liver, suggest that the basal concentration of this hormone in peripheral plasma probably does not exceed 0.1 mmug per ml.

Effect of the degree of nodularity on the survival of patients with nodular lymphomas.

The survival of patients with favorable lymphoma entered on various Eastern Cooperative Oncology Group (ECOG) studies was analyzed according to the degree of nodularity. A pure nodular pattern (NN), defined as nodularity involving 75% or more of the cross-sectional area, was found to be an important favorable prognostic indicator as compared with a nodular-diffuse pattern (ND). The median survival in 336 patients with NN of 68.2 months was significantly better than the 39.6 months in 87 patients with ND (P less than .003). The median survival in NN-lymphocytic poorly differentiated (LPD) was 77.2 months v 44.3 months for ND-LPD. NN-M median survival of 56.4 months contrasted with only 25.5 months for ND-mixed lymphocytic and histiocytic (M). The degree of nodularity as defined in this study appears to have significant prognostic implication and should be more widely used by pathologists.

Anxiety levels in patients randomized to adjuvant therapy versus observation for early breast cancer.

We studied anxiety levels in 68 patients who had been randomized to adjuvant chemotherapy v observation on two Eastern Cooperative Oncology Group (ECOG) protocols. All subjects were women who had undergone total or modified radical mastectomy for breast cancer. Immediately before breast protocol randomization and again 3, 6, and 12 months later, patients completed two self-report measures: the State-Trait Anxiety Inventory and the SCL-90. There were no consistent trends in anxiety levels over time. At each test point, patients under observation displayed higher anxiety scores than did patients receiving adjuvant therapy, but these differences failed to attain statistical significance. Power calculations indicate that these results rule out the possibility of major differences in anxiety levels among patients randomized to observation v adjuvant therapy, but a larger patient sample is required before a definitive statement can be made about smaller differences.

Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.

Solid tumors complicating Hodgkin's disease. A report on two patients with immunoglobulin deficiency.

Multiple epithelial malignant neoplasms developed in two patients with Hodgkin's disease subsequent to radiotherapy and intensive chemotherapy. At the time of diagnosis, each patient also demonstrated a serum immunoglobulin deficiency. The significance of the occurrence of solid tumors in patients following therapy for Hodgkin's disease and the significance of cellular and humoral immunodeficiency in Hodgkin's disease in relation to second cancer development were studied. We suggest the establishment of a registry of leukemias and solid tumors developing in patients treated for Hodgkin's disease and other malignant neoplasms, possibly with detailed recording of immunocompetence data.

Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy.

Forty cancer patients receiving parenteral chemotherapy were assessed for characteristics associated with the development of anticipatory nausea and vomiting (ANV). The patients who developed ANV were more likely to have increased pretreatment anxiety (p less than 0.05), greater posttreatment dizziness/lightheadedness (p less than 0.01), more severe postchemotherapy vomiting (p less than 0.01), and a delayed onset of postchemotherapy nausea and vomiting (PCNV) compared to the patients who developed neither ANV nor PCNV. However, when patients who did not develop PCNV were excluded from the analysis, the difference between the ANV and non-ANV patients remained significant only for postchemotherapy dizziness/lightheadedness (p less than 0.05). In an attempt to identify a group of variables that better predict the development of ANV, we analyzed the data for combinations of variables. Two indices were found to correctly classify ANV and non-ANV patients 71% of the time (p less than 0.05). Index A refers to the presence of at least two of the following variables, pretreatment anxiety, posttreatment dizziness/lightheadedness, and latency of PCNV. Index B refers to the presence of at least two of the following variables: pretreatment anxiety, severity of nausea, and severity of vomiting. The identification of characteristics associated with the development of ANV could lead to new intervention strategies.

A pilot study of the Functional Living Index-Cancer (FLIC) Scale for the assessment of quality of life for metastatic lung cancer patients. An Eastern Cooperative Oncology Group study.

Quality of life is an important factor in the assessment of cancer therapy, but it is difficult to define and measure. The Functional Living Index-Cancer (FLIC) was designed specifically for cancer patients under treatment. The Eastern Cooperative Oncology Group (ECOG) mounted a pilot study to assess the feasibility and sensitivity of the patient-oriented FLIC scale for assessment of quality of life. The results of this study show that the FLIC scores correlate with the functional status of patients on treatment: high scores on the FLIC prior to therapy were found to correlate with good performance status (p = 0.0001), and decreases in the FLIC score during therapy correlated with a decline in performance status (p = 0.0001), with poor performance status (p = 0.0002), and greater than 5% recent weight loss (p = 0.004). However, there was poor compliance to completion of the instrument, indicating a need for future research into this aspect of assessing quality of life in the cooperative group setting.

B-lymphoproliferative disorders: a proposed unified pathogenetic pathway.

The clinical features of lymphoproliferative diseases associated with paraproteinemia are briefly reviewed and correlated with current immunologic concepts in an effort to clarify the pathophysiology of B-lymphocyte disorders. B-lymphocyte maturation proceeds in a predictable manner from the Pre-B cell to the formation of idiotype specific plasma cells and memory B-lymphocytes. The immunoglobulin isotype produced by the mature plasma cell is determined by a site specific process of gene switching which proceeds from mu to alpha production. Lymphoproliferative diseases are the result of disordered B cell maturation and their clinical features can be explained by identifying the locus of the maturational defect.

Comparison of the effects of single versus multiple agent chemotherapy on lymphocytes assayed by the rosette technique.

The percentage of peripheral blood Total T, Active T and B-Rosette Forming Cells (RFC) were determined serially (Day 0, 1, 2, 7, and 21) following administration of single (SAT) versus multiple (MAT) agent chemotherapy. SAT caused essentially a decrease in the percentage of B-RFC. MAT resulted in profound decrease of Active T and B-RFC and to a lesser degree of Total T-RFC percentages with nadirs being reached in 48 hours. The most striking decrease involved the percentage of Active T-RFC which remained 15% below pretreatment level 7th posttreatment day. The posttreatment changes in the absolute numbers of Total T, Active T and B-RFCs following MAT were similar to that noted on the RFC percentage. Effects of the two most commonly used multiple agent treatments (COBAM and DOMF) were comparable. MAT causes a more profound decrease in the percentage of various RFCs than SAT. The differences between the nadirs of various RFC reached Day 1 and 2 with MAT versus SAT are statistically significant (p less than .001). We conclude that the effects of chemotherapy on peripheral RFC may be best evidenced by serial determination of their percentage rather than their absolute numbers. Subpopulation of the T-RFC which has been labeled Active T-RFC appears to be the best indicator of the chemotherapy effects on the lymphocyte population since they demonstrate the most profound and persistent changes.

Chemotherapy of malignant diffuse mesothelioma.

The clinicopathologic features of six pleural and one peritoneal mesothelioma were analyzed. Six patients were treated with either adriamycin or a multiple drug regimen consisting of cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil (COMF). Of those who received COMF, one obtained a complete response lasting 19 months and two had partial responses lasting 3 and 7 months. Adriamycin was administered to five patients. Two obtained a complete response lasting 19 and 7 months. Three had partial responses lasting 2, 6, and 9 months. Grading of response was often difficult requiring serial review of chest x-rays. Survival from diagnosis ranged from 2 to 39 months, with a median of 9 months. We conclude that adriamycin or COMF treatment may offer worthwhile remissions in mesothelioma and that malignant diffuse mesothelioma is more responsive to chemotherapy than previously realized.

Simultaneous cloacogenic carcinoma in dizygotic twins.

Dizygotic twins developed cloacogenic carcinoma of the anus almost simultaneously. The patients, although separated from the time they were 20-years-old, had very similar life styles. There are several reports in the medical literature of synchronous tumors in mono and dizygotic twins. It is recommended that if a cancer diagnosis is made in one twin, the other undergo workup to exclude the presence of a tumor with similar histology. The establishment of state or national twin registries would provide valuable information regarding the role of genetic and environmental factors in the development of not only cancer but also of various nonmalignant disorders.

T and B-RFC inhibiting factor in plasma from patients with active Hodgkin's disease.

We report the presence of a rosette inhibiting factor (RIF) in the plasma of patients with active Hodgkin's disease. This factor suppresses the rosette forming ability of autologous Active T, Total T, and B lymphocytes with sheep red blood cells, and tends to disappear when clinical remission is achieved. To a lesser extent, the RIF also lowers the Active T, Total T and B-RFC percentages of lymphocytes obtained from normal donors. Although carcinoma and non-Hodgkin's lymphoma patients, as a group, did not exhibit rosette inhibitive properties, certain individuals with these diagnoses did show isolated RIF activity. The RIF could be adsorbed out of plasma using peripheral blood lymphocytes (PBL) from normal controls and appears to be a large heat stable molecule which does not affect PBL viability.

Oral amphotericin for candidiasis in patients with hematologic neoplasms. An autopsy study.

Autopsy examinations were conducted in 72 patients with hematologic malignant neoplasms who received antibacterial therapy before their deaths. These patients were participants in a large double-blind study designed to assess the efficacy of oral amphotericin B in decreasing the incidence of candidal infection. The patients received either 50 mg of amphotericin B orally four times a day, or they received a matching placebo. Eight of 33 patients (24%) who had received placebo and two of 39 (5%) who had received amphotericin had histopathologic evidence of disseminated candidiasis. We conclude that in these patients with hematologic malignant neoplasms who received antibiotics within two weeks of death, the concomitant oral administration of amphotericin was effective in decreasing the incidence of systemic candidal infections, indicating that the gastrointestinal tract serves as a portal of entry for Candida albicans.

Blastic phase of agnogenic myeloid metaplasia simulating malignant lymphoma.

A patient with angogenic myeloid metaplasia in blastic transformation with unusually prominent lymphadenopathy simulating lymphoma is described. Interestingly, the initial evidence of myeloblastic transformation was present in the lymph nodes but not in the marrow. Serial bone marrow biopsies showed fibrosis throughout the course of the disease, in spite of a gradual increase in the percentage of peripheral blood myeloblasts. Aneuploidy with a marker chromosome and a Philadelphia-like chromosome was present in the lymph node, bone marrow, and peripheral blood cells. The literature is reviewed regarding the incidence of prominent lymphadenopathy and chromosome abnormalities in agnogenic myeloid metaplasia and other myeloproliferative disorders.