Serum cholesterol and human colon cancer.

Comparison of serum cholesterol levels in a matched case-control study indicates that patients with colon cancer have serum cholesterol levels lower than those of controls. In 133 pairs matched by age and sex, serum cholesterol levels were 188 +/- 42 mg/dl for cases and 213 +/- 42 mg/dl for controls (paired t-test = 5.08; P less than 0.001). Following stratification by tumor stage, significant differences in serum cholesterol levels persisted between cases with advanced tumors (Duke's classification C1, C2, and D) and controls (mean serum cholesterol difference, 41 +/- 41 mg/dl; paired t-test = 6.16; P less than 0.001) but not between cases with early tumors (Duke's classification A, B1, and B2) and controls, although the same trend was noted. Matching of 130 early tumors to advanced tumors showed that women, but not men, had a significantly lower serum cholesterol level with advancing disease. The findings support the concept that low serum cholesterol levels observed in colon cancer patients may be the result of the metabolic influence of advanced tumors, at least in women, and may not necessarily precede tumor formation.

Thymus and breast cancer--plasma androgens, thymic pathology, and peripheral lymphocytes in myasthenia gravis.

Plasma androgen sulfates were measured in 92 patients with myasthenia gravis. Plasma androgen sulfates were strongly associated with thymic pathology. The presence of germinal centers was associated with decreased androgen levels. A weak but significant positive correlation existed between androgen sulfates and lymphocyte counts. Low lymphocyte counts in patients with germinal centers were associated with subnormal androgen concentrations. Plasma androgen sulfate levels decreased immediately after thymectomy, but overall no significant differences were found between prethymectomy and post thymectomy levels. A trend toward higher concentrations of plasma androgens was noted 5 or more years post thymectomy. Plasma androgen sulfate levels in myasthenia gravis patients with breast cancer were markedly depressed. The lowest androgen sulfate levels were observed in patients who had previous bilateral breast cancer and those who, subsequent to the determination of the steroid sulfates, developed a second primary lesion of the breast.

Regional curare test in evaluation of ocular myasthenia.

In 7 of 14 patients with clinically restricted ocular myasthenia gravis, the regional curare test showed latent peripheral involvement. The test consisted of the intravenous administration of 0.2 mg d-tubocurarine into an ischemic arm followed by repetitive supramaximal percutaneous electrical stimulation of the median or ulnar nerves. This produced a decrease in the amplitude of the initial evoked potential and a decrement of greater than 10% in the amplitude of the succeeding three to five potentials at rates of 3, 5, or 15 stimuli/sec. Three patients underwent transcervical thymectomy with subsequent improvement in both electrical and clinical findings. Evaluation of all patients with ocular myasthenia gravis should include regional curare testing of clinically uninvolved peripheral nerves. Thymectomy should be considered for patients with abnormal results.

Plasmapheresis in refractory generalized myasthenia gravis.

A group of 16 patients with severe generalized myasthenia gravis (MG) (five with thymoma) that was resistant to anticholinesterases, thymectomy, and corticosteroids were treated by plasmapheresis. Twelve patients showed an excellent clinical response. Plasmapheresis is an effective treatment modality for many patients with severe generalized MG resistant to other forms of therapy. Unfortunately, the beneficial results are only transient and periodic plasmapheresis treatments are necessary.

Electrophysiologic diagnosis of myasthenia gravis and the regional curare test.

Two hundred and fifty consecutive patients were evaluated for myasthenia gravis with repetitive supramaximal stimulation of peripheral nerves and regional curare administration when necessary. Among patients with definite generalized myasthenia gravis, 72 percent had abnormal responses to repetitive supramaximal stimulation alone and another 17 percent had abnormal responses after regional curare administration. Among those with possible generalized myasthenia gravis, 15 percent had abnormal responses to repetitive supramaximal stimulation and another 12 percent had abnormal responses after regional curare administration. Of those with only ocular symptoms, 46 percent had abnormal responses to repetitive supramaximal stimulation before or after regional curare administration, suggesting generalized involvement. Myasthenia gravis has not developed subsequently in any of the equivocal patients with negative electric tests. We have found these electric procedures to be simple, safe, and at least as effective as other methods in diagnosing myasthenia gravis.

Electrophysiologic evaluations of thymectomy in myasthenia gravis. Preliminary findings.

Electric testing was performed in 106 myasthenia gravis patients before and after transcervical thymectomy. Twenty-nine were followed for 3 to 24 months. Results were correlated with thymic pathology, duration of disease, age at operation, and follow-up clinical status. Electric improvement was significantly greater in patients without thymic germinal centers or with only rare to occasional germinal centers, in patients operated on within 1 year after onset of symptoms, and in patients under age 30. Electric improvement immediately after thymectomy heralded later clinical improvement in those patients without germinal centers or with rare to occasional germinal centers. Electric-clinical correlations were excellent in patients with longer follow-up. Serial electric testing provides an objective evaluation of the patients' clinical status post-thymectomy.

Studies in myasthenia gravis. Pyridostigmine-C14 metabolism after thymectomy.

Pyridostigmine-carbon 14 (P-C14) excretion studies in myasthenia gravis patients who had had thymectomies failed to produce any significant difference from results observed in myasthenic patients who had not had thymectomies. Thus, change in P-C14 metabolism cannot help explain decreased anticholinesterase requirements and electromyographic changes observed in some patients following thymectomy.

Studies in myasthenia gravis: early thymectomy. Electrophysiologic and pathologic correlations.

Indications for thymectomy in myasthenia gravis have been recently expanded to include all cases with extraocular symptoms as a result of the minimal morbidity and negligible mortality of the transcervical approach. As increasing numbers of patients with myasthenia gravis, covering the entire spectrum of generalized disease, have been added to the thymectomy population, a more accurate evaluation of the effects of the operation is possible. Our experience with 353 patients who have undergone thymectomy indicates that early thymectomy, particularly in patients who do not have germinal centers, is followed by early remission of the disease. Delayed remission after thymectomy is related to the duration and severity of the disease, and to presence of thymic germinal centers. Germinal centers were found more frequently in patients with long duration of the disease and in patients in whom the disease had progressed to respiratory involvement. Marked improvement in electromyographic findings immediately after thymectomy was observed in the majority of patients who had had the disease for 1 year of less and where germinal centers were absent. The percentage of malignant thymomas was higher in patients who underwent thymectomy 1 year or more after the onset of symptoms of myasthenia gravis. These data indicate the importance of early thymectomy while the disease is still in the mild stages. Transcervical thymectomy is the treatment of choice as it is followed by a higher percentage of remissions and by less morbidity than other forms of treatment.

Clinical experience in more than 2000 patients with myasthenia gravis.

The vast strides in terms of pathophysiologic understanding which have been made in the past 25 years of research in myasthenia gravis are remarkable. This period of time has also seen the evolution of many applicable technological advances to better our care of these patients. Myasthenia's place in the autoimmune family of diseases has been demonstrated. No clear-cut strategy resulting from these discoveries has, however, been more than one of temporary relief or clinical improvement. In our center over these years the performance of early thymectomy in all cases of generalized myasthenia seems to be the one demonstrably reliable technique available. The effect of this procedure on coexisting neoplasia and other autoimmune disease suggests continuing avenues of investigation.

Perioperative blood transfusion has prognostic significance for breast cancer.

The transfusion-induced immune suppression that prolongs kidney graft survival for transplant patients may be detrimental to patients with malignancies. We studied the relationship of blood transfusion to the disease-free survival of 169 patients with operable breast cancer who had undergone mastectomy with axillary dissection at Mount Sinai Hospital between 1964 and 1972. The cumulative 5-year disease-free survival rate for patients who had received transfusions was 51% compared with 65% for patients who had not received blood (p = 0.0210). The two groups of patients were comparable in age, stage, discharge hemoglobin values, proportion of radical mastectomies, and duration of follow-up. Admission hemoglobin values were lower and operative blood loss was higher among patients who had received transfusions, and significant survival differences were noted in relation to operative blood loss: 69% of women with estimated blood loss less than the mean of 370 ml were free of disease at 5 years compared with 50% of women with higher intraoperative losses (p = 0.0279). However, the first year after operation the association of survival with transfusion was highly significant (77% for those who had received transfusions, 94% for those who had not, p = 0.0096), whereas survival rates in relation to operative blood loss differed by only 7% during the same interval (p = 0.1182). These results indicate that perioperative blood transfusion may be a significant prognostic factor for patients undergoing mastectomy for operable breast cancer.

Association of tumor differentiation with caffeine and coffee intake in women with breast cancer.

Caffeine, which has been linked to benign breast disease, has an antineoplastic effect in experimental animals, whereas in tissue cultures it inhibits mitoses and induces cell differentiation. We examined caffeine and coffee intake in 101 women with breast cancer to determine whether either or both influence cell differentiation in tumors as well. Nutrient analysis was performed by the Nutrition Coding Center of the University of Minnesota with the Nutrition Data system from the National Heart, Lung, and Blood Institute. Stepwise logistic regression, with tumor differentiation (well and moderate versus poor) as the dependent variable, was used. The analysis indicates that caffeine and/or coffee intake has a significant association with tumor differentiation as women with moderately to well-differentiated tumors had higher caffeine and coffee intake. This raises the question whether caffeine or coffee consumption may help induce cell differentiation and slow tumor growth.

The association of carcinoembryonic antigen and peripheral lymphocytes.

A significant association between carcinoembryonic antigen (CEA) assay titers and peripheral lymphocyte counts was observed in 148 simultaneous determinations. The association was present in a high cancer risk study group of patients with myasthenia gravis and in a control group of patients with granulomatous disease of the bowel, ulcerative colitis, and colonic neoplasms. A highly significant difference in the percentage of positive CEA assays in relation to lymphocyte counts was noted both in the study and control groups. In the study group CEA was positive in seven of 41 patients (17 percent) with counts above 2,000 per cubic millimeter, and in 26 of 56 (43 percent) of those with lower counts (X2 = 9.06, p smaller than 0.005). The corresponding percentages in the control group were 20 and 61 percent (X2 = 5.60, p smaller than 0.025). A significant difference between the means of lymphocytes in groups with different CEA titers also was found (F = 6.77, p smaller than 0.05). The finding of lower peripheral lymphocytes and/or higher titers of CEA in groups with increased risk of cancer, i.e., severe myasthenia gravis, patients with thymomas and patients with long history of granulomatous disease of the bowel, suggests on association between the results of the two tests and cancer risk. The observations indicate that the yield of CEA assay in cancer detection may be higher in patients with lwo lymphocytes, and that these determinations used in conjunction may serve better as diagnostic and prognostic aids in patients with known neoplasms or in high cancer risk groups.

Preoperative carcinoembryonic antigen levels in colorectal carcinoma.

The records of 145 patients with colorectal carcinoma who had preoperative carcinoembryonic antigen (CEA) levels measured were evaluated. Preoperative CEA levels were correlated with pathological stage and tumor locations. Increasing levels of CEA were found with advanced stage of disease. Metastatic tumors could be accurately predicted in large percentage of cases. Right-sided colon tumors had lower levels of CEA, compared to left-sided lesions.

Surgery for nonpalpable breast lesions.

Nonpalpable lesions detected on mammograms were localized in 475 women between 1976 and 1988 by means of the spot method. A malignant neoplasm was noted in 149 patients (31%), including 69 (33%) of 206 with clusters of microcalcifications, 16 (41%) of 39 with calcifications associated with densities and 64 (28%) of 230 with nonpalpable masses. Infiltrating lesions were present in 89 (60%) of 149 patients. Among women with infiltrating lesions who had axillary dissection, 14 (21%) of 67 had positive nodes. In younger women, microcalcifications were more likely to represent neoplasms, masses frequently represented invasive tumors. Among patients with invasive malignant neoplasms who had calcifications, 39% had positive axillary lymph nodes. Spot localization, rather than monitoring, seems appropriate in young women with microcalcifications suggestive of malignant neoplasms and older patients with nonpalpable masses to achieve earlier and more effective treatment of biologically significant occult neoplasms.

Prognosis in occult thymomas in myasthenia gravis following transcervical thymectomy.

Thymomas were noted in 239 (11%) of 2097 myasthenic patients followed up at our institution. Among 996 patients who had undergone thymectomy, 191 patients (19%) had thymomas compared with 48 (4%) of 1101 patients treated without surgery. A definitive diagnosis of thymoma was not made until after thymectomy in 61 patients (35%); in patients not treated with thymectomy, 23% of associated tumors were diagnosed at autopsy. Patients with occult thymomas treated with the transcervical approach had a clinical course superior to those with tumors diagnosed prior to surgery and treated with the transsternal approach. Most of the advantage could be attributed to the association of occult thymomas with small tumor size and to the association of the latter with absence of invasiveness. Small tumor size was significantly associated with higher remission and lower mortality as shown in a proportional hazards analysis. Occult thymomas were accessible through the transcervical approach, with some operations necessitating a complementary mediastinotomy. Thymectomy, through the transcervical approach if technically feasible, is of benefit to all patients, has minimal morbidity, and should be performed early in the course of the disease as a diagnostic and therapeutic intervention since the risk of occult thymomas in patients with myasthenia gravis is high.

Transcervical thymectomy for thymoma in myasthenia gravis.

The results of thymectomy performed through a transcervical approach in 37 myasthenic patients with thymomas is reported and compared with results in 97 patients who had thymomas removed through a transsternal approach. In 29 of the former patients the thymomas were unsuspected and found at the time of thymectomy, and in 8 a preoperative chest roentgenogram was suspicious for the presence of a tumor. In the transcervical group there were only 4 invasive thymomas, while in the transsternal group there were 32. In the transcervical group there was no evidence of recurrence in the patients with unsuspected thymomas, and one recurrence in the group with suspected thymomas. In the transsternal group eight patients had known recurrence or persistent disease. The transcervical approach seems appropriate for the removal of small thymomas discovered at the time of thymectomy or suspected from the preoperative work-up.

Case report: Thymectomy-induced remission of acquired autoimmune hemolytic anemia in an adult with myasthenia gravis.

A 57-year-old woman with diabetes mellitus, hypothyroidism, idiopathic thrombocytopenic purpura, myasthenia gravis, systemic lupus erythematosus, atopy, and basal cell cancer of the skin developed a severe Coombs'-positive autoimmune hemolytic anemia which was resistant to treatment with large doses of azathioprine, cytoxan, and prednisone. One year after transcervical thymectomy the hemolytic anemia disappeared and the patient has maintained a normal hemoglobin and negative Coombs' test without immunosuppressants even since. We believe this case report to be the first recorded instance of thymectomy-induced remission of autoimmune hemolytic anemia in an adult.