Elevations in serum copper, erythrocytic copper, and ceruloplasmin concentrations in smokers.

Previous investigators have reported significant elevations of serum copper and ceruloplasmin levels in lymphoma patients and subjects using estrogen, but have not taken into account the smoking habits of these populations. In order to determine whether smoking had any effect on these variables, the authors examined five groups for serum and erythrocytic copper and ceruloplasmin levels: 40 healthy subjects, 14 users of oral contraceptives, 25 smokers, 14 nonsmoking pretreatment lymphoma patients, and eight treated lymphoma patients. Significant elevations of serum copper and ceruloplasmin in pretreatment lymphoma patients, treated patients, and estrogen users were found, confirming previous reports. In addition, all groups had elevations of erythrocytic copper compared with the healthy subjects. Also, significant elevations of serum copper (P less than .0053) and ceruloplasmin (P less than .0001) were found in smoking relative to nonsmoking subjects. No correlation between duration of smoking and these elevations was found.

PIP: Levels of serum and erythrocytic copper and ceruloplasmin are compared among groups of smoking and nonsmoking individuals, some of whom have taken oral contraceptives 97 subjects were studied. 40 were healthy subjects who were nonsmokers, and 4 users of oral contraceptives, 25 smokers, and 4 nonsmoking pretreatment lymphoma patients, and 8 patients under treatment for lymphoma were also studied. There were elevations of serum copper and ceruloplasmin activity for all 5 groups. By Student's t test, there were elevations of serum copper, erythrocytic copper, and ceruloplasmin in all 4 groups compared with healthy nonsmoking subjects at least at the P.01 level,; it was P.05 for erythrocytic copper smokers. Significant correlations of linear relationship between serum copper and ceruloplasmin were noted for all populations except smokers. No correlation was apparent between duration of smoking, or frequency of usage and elevations of serum copper, erythrocytic copper, or ceruloplasmin.

Management of abdominal hemophilic pseudotumor.

The abdominal hemophilic pseudotumor is a rare but frequently disabling and life-threatening complication in patients with severe hemophilia. Our patients were observed for a considerable period of time to document progressive enlargement of the pseudotumor and increasing disability from severe pain, nerve compression, or leg swelling. The decision to operate was made on the basis of incapacitating symptomatology or fear of impending rupture. Although the complications resulting from operation may be major, with the current availability of large amounts of factor VIII and activated prothrombin complex concentrate, excision of this lesion can be performed without concern for the hazard of uncontrollable hemorrhage. Late recurrence of the pseudotumor may necessitate further operative management.

Splenectomy for thrombocytopenia due to secondary hypersplenism.

The response to splenectomy of patients with thrombocytopenia due to secondary hypersplenism is frequently unpredictable. Our experience indicated that splenectomy is seldom justified for this indication in patients with chronic myelogenous or chronic granulocytic leukemia. Since patients with chronic lymphocytic leukemia, hairy-cell leukemia, and stage IV lymphoma may have a more prolonged life expectancy, removal of the spleen brings about a satisfactory response of thrombocytopenia in some instances. Elevation of platelet counts after splenectomy in patients with agnogenic myeloid metaplasia is most likely to occur in women with the primary form of the disease. In other nonmalignant conditions, splenectomy has resulted in a satisfactory response in the majority of patients.

Splenectomy in the treatment of hemolytic anemia.

In 113 patients with hemolytic anemia splenectomy was performed, without mortality and with minimal morbidity. Fifty-three patients with congenital spherocytosis and two with congenital elliptocytosis had postoperative increases in hematocrit to normal or near-normal levels. Three patients with pyruvate kinase deficiency and three with thalassemia variants were improved. Splenectomy in 52 patients with autoimmune hemolytic anemia resulted in an excellent response in 64% (no further steroid therapy) and an improved status in another 21% (prednisone requirements, 15 mg/day or less). For conditions other than congenital spherocytosis, in which splenectomy is uniformly of value, a decision to remove the spleen should be based on severity of the hemolytic process, failure to respond to other therapies, and the potential for achieving significant improvement in anemia and other associated cytopenias.

The spectrum of pulmonary embolism: twenty years later.

A ten-year analysis of the prevalence of pulmonary embolism found at autopsy examination has been repeated 20 years after a prior study. The frequency of all pulmonary embolism (12.3%) and of "major" pulmonary emboli (7.1%) remains essentially unchanged from that detected 20 years previously (13.6% and 8.6%). Less than 10% of patients had the clinical diagnosis of deep leg vein thrombosis, and only 9.3% had a definitive diagnosis of pulmonary embolism made during life. A sixfold variation in quarterly frequency and a twofold variation in annual prevalence were noted. Since these wide fluctuations in frequency are present, any assumptions regarding a changing disease pattern must be made with great caution. There is no evidence that fatal pulmonary embolism has decreased in frequency in recent years. An effort should be made to increase rate of detection of thromboembolic disease by more widespread use of one or more of the recently developed diagnostic procedures, or a larger segment of the hospital population at risk should receive prophylactic therapy with "low-dose" heparin sodium.

'Secondary' operative staging of patients with lymphoma.

Secondary operative staging (diagnostic celiotomy after initial lymphoma staging and treatment) is of value in selected patients with Hodgkin's disease if, after appropriate clinical staging, there remains a reasonable doubt concerning the presence of residual or recurrent lymphoma. In our experience, although signs indicating possible recurrence were present in 35 patients, only 20 of these were found to have Hodgkin's disease within the abdomen at operation. These findings allowed us to restrict our intensive therapy to those with documented disease and to withhold potentially harmful treatment from the remaining subjects who on follow-up have shown no evidence to date of subsequent recurrence within the abdomen. The utilization of secondary operative staging in ten patients with non-Hodgkin's lymphoma has been less productive and is not recommended on the basis of our limited current experience.

Deep venous thrombosis and postsplenectomy thrombocytosis.

Eighty-six patients undergoing elective splenectomy have been investigated preoperatively and postoperatively by serial platelet counts and leg scanning using iodine 125-labeled fibrinogen. The presence of deep leg vein thromboses detected by labeled fibrinogen was confirmed by dye phlebography. In only five patients (6%) did deep venous thrombosis develop. In none of these five patients did an elevation in platelet count to 600,000/cu mm develop before or at the time of development of the thrombosis. None of 21 other patients who did have a rise in platelet count greater than 1,000,000/cu mm had evidenced of venous thrombosis. These data do not substantiate the need for routine prophylactic antithrombotic therapy in patients in whom postsplenectomy thrombocytosis develops.

Venous thromboembolism. Prevalence, risk factors, and prevention.

Venous thromboembolism is a major source of morbidity in hospitalized patients. A knowledge of the factors that increase the risk of development of this condition can be utilized to plan appropriate and cost-effective preventive management.

Splenectomy for cytopenias associated with systemic lupus erythematosus.

Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment.

Felty's syndrome: when is splenectomy indicated?

The spectrum of disease was assessed in 43 patients with Felty's syndrome. Twenty-three underwent splenectomy. Although complete remission of neutropenia occurred in only two nonoperated patients, most of the patients had no serious infections during the subsequent period of observation. Operative morbidity was minimal in the splenectomized patients. On the basis of natural history of this condition, splenectomy should probably be restricted to neutropenic patients with serious or recurrent infections, patients with severe anemia requiring transfusions, those with the rare circumstance of profound thrombocytopenia, and those with non-healing leg ulcers.

Iatrogenic splenic injury.

In a previous report from this institution, 21% of splenectomies performed between 1957 and 1967 were for iatrogenic injury to the spleen. In the present study, encompassing the years 1971 to 1987, the frequency of iatrogenic splenic injury was reduced to 9% (134 of 1,557 splenectomies). However, there has been no evidence of a progressive decrease in accidental splenic injury from 1971 to 1987. Although the number of injuries related to operations on the stomach or repair of hiatus hernia have declined somewhat in the past decade, the incidence of splenic injuries secondary to colectomy and nephrectomy has not changed appreciably, and injuries linked to complex operations on the aorta and its branches (19 cases) have increased. No evidence could be found that morbidity was increased if the splenic injury is promptly recognized and managed by splenectomy. However, 13 of these 134 patients required reoperation for control of continued bleeding from unrecognized iatrogenic splenic trauma. Constant awareness of the continued prevalence of this operative complication and the mechanisms by which it is produced should enable surgeons to lessen its frequency and potential sequelae.

Anticoagulant therapy.

This is a brief review of some of the more important aspects of pharmacology and clinical management of anticoagulant therapy for venous thromboembolism. Some controversial aspects of treatment with respect to drug dosage, laboratory monitoring, and intensity and duration of therapy have been discussed. Thromboembolic complications can be reduced by extending the duration of anticoagulant therapy to a minimum period of 4 months after hospital discharge. Longer periods of treatment may be necessary in patients with recurrent deep venous thrombosis or pulmonary embolism. Hemorrhagic complications can be minimized by proper attention to laboratory monitoring and awareness of drug interactions and side effects.

Indications for and morbidity associated with operative staging in patients with lymphoma.

Operative staging of patients with lymphoma has made an important contribution to the more accurate planning of treatment of this disease. Concomitant improvements in therapy have led to an increase in 5 year survival, particularly in patients with Hodgkin's disease. Nevertheless, considering risk versus benefit, several groups of patients might be spared increased morbidity from postoperative infection by restricting the operation to patients with stage I non-Hodgkin's lymphoma and to patients with Hodgkin's disease, stages I to III, without B symptoms. Groups having a greater risk of infection include all patients with non-Hodgkin's lymphoma and patients with Hodgkin's disease and B symptoms in whom operation is indicated. These exclusions from operative staging may not apply if accurate definition of the extent of disease is essential to evaluation of a new therapeutic program being assessed by a prospective randomized clinical trial.