Biomedical subjects
Publications and source records attributed to D C Doll.
Three cases of peripheral T-cell lymphocytosis associated with thymoma are described. Each patient had a malignant, predominantly lymphocytic thymoma with resolution of lymphocytosis upon treatment of the epithelial neoplasm. These findings suggest that lymphocytosis complicating thymoma is a paraneoplastic phenomenon and is not part of the neoplastic process.
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Previous studies have indicated relative resistance to chemotherapy in the myelodysplastic syndromes (MDS) and associated acute leukaemia. To determine if multidrug resistance may contribute to chemoresistance in these disorders, we studied bone marrow specimens for P-glycoprotein expression (P-GP) by immunocytochemical staining with monoclonal antibodies reactive with cytoplasmic (C219) or surface epitopes (MRK16) of P-GP. Forty-five case specimens from 43 patients were studied, including 32 cases of primary MDS, seven cases of acute myeloid leukaemia (AML) following MDS, and six therapy-related haematological disorders. Cytogenetic analysis was available on 36 specimens. Two staining patterns were detected: (1) cytoplasm and plasma membrane, and (2) staining restricted primarily to the nuclear-cytoplasmic junction. P-GP was detected in seven (22%) cases of primary MDS, four (57%) cases of AML evolving from MDS, and five (83%) cases of therapy-related haematological disorders. Expression of P-GP was restricted to blasts and leukaemic monocytes, and was otherwise absent from terminally differentiated blood cells. Analysis of the relation between P-GP expression and reactivity with the human progenitor cell antigen CD34, revealed a highly significant association (P = 0.001). P-GP reactivity was distributed equally among normal and abnormal karyotypes and did not correlate with specific cytogenetic abnormalities. These findings indicate that multidrug resistance in MDS and karyotypically-related haematological disorders is closely linked to a stem cell phenotype and may contribute to chemoresistance in these disorders.
Epidural spinal cord compression is a common complication of malignancy. In the majority of cases, the primary site is known at diagnosis or is evident following limited investigation. During the period January 1975 to December 1987 we encountered seven cases of tumor of unknown origin presenting as cord compression. Myelography detected the site of cord involvement in six cases, and computed tomography of the spine was utilized in one case. All seven patients underwent laminectomy. Histologic diagnosis was adenocarcinoma in four cases, squamous in one case, and large cell undifferentiated carcinoma in two cases. Evaluation for a primary site was unrewarding. Prognosis was poor, with a median survival of 10 weeks. Only one patient had a satisfactory response to treatment.
The initial care of patients with acute nonlymphocytic leukemia can be lifesaving. Such patients are most often treated at tertiary care centers where resident physicians, working under the supervision of a subspecialist, are responsible for the diagnosis and initial treatment. During the first 48 hours, the house officer must recognize and understand the management of perilous complications such as hyperleukocytosis, hemorrhage, and infection. Specific lifesaving measures will grant the patient and his physicians sufficient time to reach a decision regarding the initiation of curative induction chemotherapy.
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To determine the clinical characteristics of patients presenting with malignant ascites, as well as means of evaluating the outcome of patients with the disease, a retrospective review was conducted of all cases of malignant peritoneal effusions diagnosed from 1978 to 1987 at a University Hospital and a Veterans Administration Hospital. Of 65 patients with malignant ascites (40 women; 25 men), the primary site was known in 51 cases (80%). Common sites in women were the ovaries, endometrium, and cervix; in men, common sites were the colon, rectum, and stomach. For five women and nine men the primary site was unknown. Median survival from diagnosis was 7.5 days (mean, 43 days; range 1-256 days). Chest radiograph and abdominal computed tomography (CT) scan did not disclose the occult primary. An occult primary was detected while the patient was alive in only two cases and at autopsy in two other patients. Due to the poor prognosis for this disease, we do not recommend an aggressive approach to malignant ascites of unknown origin, except perhaps in women, in whom ovarian cancer should be suspected.
Of 129 patients with small cell lung cancer (SCLC) who underwent bone marrow examination for staging, 39 (30%) had bone marrow involvement. Only three of 129 patients (2.3%) had bone marrow involvement as the only site of metastatic disease. When patients with bone marrow metastasis were compared with patients whose bone marrow was normal, there were significant differences in serum levels of lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (AP), albumin, and sodium (Na). We found no clinically significant difference in survival between patients with extensive disease with or without bone marrow involvement. Serum Na, albumin, SGOT, and uric acid were important prognostic determinants of survival. Based on the results of this study, we do not recommend routine bone marrow examinations in the staging of SCLC.
Results of bone marrow biopsy were retrospectively evaluated in 120 previously untreated patients with Hodgkin's disease. The incidence of bone marrow involvement was 13%. All patients with marrow invasion had B symptoms and/or clinically advanced disease. When patients with bone marrow involvement were compared to those without there were significant differences in the incidence of B symptoms, the clinical stage, hemoglobin levels, leukocyte counts, platelet counts, and serum levels of lactate dehydrogenase and alkaline phosphatase. None of 59 patients with clinical stage IA and IIA had evidence of marrow invasion. This study demonstrates that trephine bone marrow biopsy is of value in detecting marrow involvement in specific subgroups of untreated patients with Hodgkin's disease, i.e., those patients with constitutional symptoms and/or clinical stage III or IV. However, bone marrow biopsy adds little to the initial staging of patients with clinical stage IA and IIA. Routine use of this procedure in such patients may be unnecessary.
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During the third-year medicine clerkship, students were instructed in online computer Physician Data Query (PDQ) searches. Each student completed computer searches in at least one of five tumor topics. Students assigned to selected tumor topics performed significantly better on test questions in their assigned topic as compared to the scores of students who were not assigned that topic. Although students were encouraged to use the PDQ ad libitum, within three months of completing the clerkship, only 22 students (20%) had conducted additional searches. We conclude that PDQ instruction may enhance students' knowledge about cancer. Student instruction can be effectively completed with minimal computer time. The results from our program evaluation and the limited student use following completion of the clerkship suggest that we should identify another user group, such as senior housestaff, to generate greater interest and more frequent use of the PDQ.
A predisposition to thrombosis in patients with procainamide-induced lupus anticoagulants is previously unrecognized. We describe two patients treated with procainamide who experienced acute thromboembolic events temporally associated with development of the lupus anticoagulant. One patient had a deep venous thrombosis and pulmonary embolism, while the other patient had a cerebrovascular accident. In both patients, coagulation parameters corrected with interruption of procainamide therapy. We suggest that thrombosis may complicate treatment with procainamide in patients who develop the lupus anticoagulant.
Fifty-one patients with primary myelodysplastic syndrome were prospectively evaluated using a scoring system based on the presentation blood and bone marrow findings. Twenty-four patients (47%) evolved to acute nonlymphocytic leukemia. Stepwise regression model showed that the scoring system was the only significant variable for predicting transformation to acute leukemia (p = 0.0007, sensitivity 70.8%, specificity 77.8%). Seventy-six percent of patients with a score of 14 or greater developed acute leukemia compared to 19% with a score of 13 or less. Median survival of the entire group was 10 months. The most important prognostic factor for predicting survival was the scoring system (p = 0.0001). Survival correlated inversely with the score. This scoring system may be useful in the management of patients with myelodysplasia.
Dysplastic hematopoiesis associated with erythrocyte macrocytosis is a morphologic hallmark of myelodysplasia. We report the cases of six patients with myelodysplasia in which acanthocytosis was the predominant red blood cell (RBC) abnormality. In each case acanthocytes represented 5% to 10% of circulating RBC forms and was the primary reason for referral in two cases. None of the patients had comorbid conditions known to be associated with acanthocyte formation. Myelodysplasia should be considered in the differential diagnosis of acanthocytosis, particularly in the anemic, elderly individual. Acanthocytosis may be a harbinger of an unrecognized, hematologic stem-cell disorder.
The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic and ineffective hematopoiesis and a varying risk of transformation to acute leukemia. Although the natural history of these syndromes is variable, several factors appear to be of prognostic importance, including the French-American-British classification, the karyotype, in vitro colony formation, and others. The pathogenesis of the myelodysplastic syndrome is not known, but recent evidence suggests that alterations of cellular oncogenes may be a causative factor. There is no standard therapy for myelodysplasia, and thus novel approaches to patient management are warranted.
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Heavy metal poisoning can cause a variety of hematologic disorders. Exposure to heavy metals is ubiquitous in the industrial environment and must be considered in the differential diagnosis of many types of anemia. The heavy metals most commonly associated with hematologic toxicity are arsenic and its derivative arsine, copper, gold, lead, and zinc. A few distinctive clinical features characterize the hematologic manifestations of many occult heavy metal poisonings. These features have a limited differential diagnosis. A knowledge of these clinical features can assist the astute clinician in making the correct diagnosis.