Angelos E. Papatestas

Effects of thymectomy in myasthenia gravis.

Factors influencing onset of remission in myasthenia gravis were evaluated in 2062 patients, of whom 962 had had thymectomy. Multivariate analysis showed that appearance of early remissions among all patients was significantly and independently influenced by thymectomy, by milder disease, and by absence of coexisting thymomas. Patients with mild generalized symptoms treated with thymectomy reached remission more frequently, even when compared with those with ocular myasthenia treated without surgery. Short duration of disease before thymectomy in mild cases was another factor associated with earlier remissions. Mortality for all patients was significantly and independently influenced by severity of symptoms, age, associated thymomas, and failure to remove the thymus. Patients without thymectomy and with thymomas had, in addition, earlier onset of extrathymic neoplasms. Morbidity after the transcervical approach was minimal. This study demonstrates that early thymectomy by the transcervical approach, when technically feasible, has significant clinical advantages over the transthoracic approach and should be advocated for all patients with myasthenia gravis, including those with ocular disease.

Cholesterol and obesity as prognostic factors in breast cancer.

Analysis of disease‐free survival rates in 374 women with operable breast cancer revealed that preoperative weight, particularly in combination with serum cholesterol, is a significant prognostic determinant. Overall, women weighing under 150 pounds had a significantly higher cumulative five‐year disease‐free survival rate (67%) compared with women weighing more (49%) (z = 2.2298, P = 0.026). Women with low serum cholesterol levels had better cumulative five‐year disease‐free survival (67%) than women with high serum cholesterol levels (58%) (z = 1.1008, P = 0.27). The combination of high weight and high serum cholesterol levels was associated with an extremely poor cumulative five‐year disease‐free survival (32%) compared with that observed for women in whom values of either, or both, variables were low (68%) (z = 3.7843, P = 0.0004). These patterns in disease‐free survival persisted even after controlling for tumor stage. The findings indicate that weight and cholesterol, in addition to their previously reported effect on the risk of breast cancer development, influence significantly the subsequent course of the disease.

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.

Sensitivity to vecuronium in myasthenia gravis : a dose-response study

A cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle were used to determine the potency of vecuronium in 20 normal patients and in ten patients with myasthenia gravis under thiamylal, N2O, O2, fentanyl anaesthesia. The mean (± SEM) values for ED50, ED90, and ED95 in the normal patients were 19 ± 1, 31 ± 1 and 36 ± 2 μg · kg− 1, respectively. Myasthenic patients showed increased sensitivity to vecuronium, the mean values for ED50, ED90, and ED95 were 10 ± 2, 17 ± 2 and 20 ± 3 μg · kg− 1, being50, 55 and 56 per cent of normal, respectively. We did not demonstrate a difference in sensitivity to vecuronium between those myasthenic patients who received pyridostigmine preoperatively and those who did not, nor among those chronically treated with corticosteroids, compared with those who were not.RésuméUne dose cumulative plus une technique de perfusion et une surveillance électromographique intégrée du muscle interosseux dorsal fut utilisée afin de déterminer la puissance du vécuronium chez 20 patients normaux et chez dix patients atteints de myasthénie grave sous thiamylal, N2O, O2, et fentanyl. Les valeurs moyennes (± SEM) du ED50, ED90 et ED95 chez les patients normaux étaient de 19 ± 1, 31 ± 1 et 36 ± 2 gmg · kg− 1 respectivement. Les patients myasthéniques ont démontré une augmentation de la sensitivité au vécuronium, les valeurs movennes de la ED50, ED90 et ED95 furent 10 ± 2, 17 ± 2 et 20 ± 3 μg · kg− 1 étant respectivement 50, 55 et 56 pour cent de la normale. On n’a pas démontré de différence avec les patients avant reçu de la pyridostigmine en période préopératoire et ceux qui n’en n’ont pas reçue, de même qu’on n’en a pas trouvé avec ceux qui étaient traités aux corticostéroīdes comparé à ceux qui ne l’étaient pas.

Thymomas in patients with myasthenia gravis.

The records of 141 patients with myasthenia gravis who had thymomas were reviewed. In this series there were 69 noninvasive tumors and 52 invasive tumors. The five year survival for all patients was 60%, with the invasive group demonstrating a poorer prognosis than the noninvasive. The remission rates for the whole group (both invasive and noninvasive) of myasthenics was quite low (7%). Although the overall survival of this series of patients was relatively high, it is felt that by earlier diagnosis and a more aggressive surgical approach their prognosis will be even better.

Peripheral lymphocyte counts in breast carcinoma: An index of immune competence

A retrospective study of 305 patients with breast carcinoma provides evidence that pretreatment lymphocyte count levels serve as an index of the hosts immune competence. An inverse correlation between the stage of the disease and the lymphocyte counts was observed among patients in the younger age groups. Patients in all stages remaining free of metastases in the first 5 postmastectomy years had significantly higher pretreatment counts than those who developed metastases and/or second primaries. These observations give further insight into the host–tumor interaction in breast carcinoma and indicate that difference in lymphocyte counts, previously attributed to treatment modalities that influence lymphocyte levels and cellular immune responses (radiotherapy, chemotherapy), may be completely independent and may rather reflect the hosts responses to tumor growth.

The prognostic significance of peripheral lymphocyte counts in patients with breast carcinoma

A retrospective study evaluating five‐year survival rates in relation to pretreatment lymphocyte counts was undertaken in 453 patients with breast carcinoma. Patients with early tumor stages had higher pretreatment lymphocyte counts than those with advanced tumors: five‐year survival in patients with pretreatment counts above 2000 per mm3 was 87% in Stage I, 67% in Stage II, and 57% in Stage III, while the comparable figures in patients with lower counts were 82%, 51%, and 29%. The differences in five‐year survival rates for Stage II and III were significant: z = 1.6955, p = 0.046 and z = 1.8841, p = 0.03. Similar differences were noted in the disease‐free, five‐year survival rates. The corresponding figures in the three tumor stages for patients with counts above 2000/mm3 were 80%, 63%, and 53%, while those for patients with lower counts were 74%, 44%, and 18%. The differences in Stage II and III were also statistically significant: z = 1.8430, p = 0.33 and z = 2.592, p = 0.005 respectively. The possibility that the presence of suppressant factors related to the thymus may influence levels of lymphocytes was evaluated. Comparison of pre‐thymectomy and postthymectomy lymphocyte counts in a control group of patients who had thymectomy for myasthenia gravis revealed a gradual increase of lymphocytes following thymectomy. The increase was significant at the second year following thymectomy. These observations indicate that lymphocyte counts may serve as prognostic indicators in patients with breast cancer. Low lymphocyte counts may be related to the presence of suppressor substances.

Parity and prognosis in breast cancer.

Analysis of five‐year disease‐free survival rates in 608 women with operable breast cancer revealed that the reproductive history is a significant prognostic determinant. Overall parous women had a significantly higher cumulative five‐year disease‐free survival rate (60%), compared to the nulliparous (46%) (z = 2.5, p = 0.012). Significant differences were also noted when gravidity in addition to parity was taken as the determinant. The corresponding disease‐free survival rates were 61% and 50%, respectively (z = 1.98, p = 0.048). Five‐year survival rates were influenced in a similar manner by these variables but the observed differences were less significant. The trend toward higher survival rates in parous and gravidae women were noted in all tumor stages but achieved statistical significance only in stage III. The findings indicate that parity and gravidity affect not only the risk of breast cancer development but also the subsequent course of the disease. Parity seems to be a stronger risk and prognostic factor than gravidity.

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.

Preoperative and postoperative immunological evaluation of patients with colorectal cancer

Twenty‐two patients with cancer of the colon and rectum were studied: preoperative and postoperative cell‐mediated and humoral immune factors were assessed, and local concentration of immunoglobulins in tumor tissue and in normal mucosa were measured. Lymphocyte function was found to be reduced in 50% of stage A and B and 66% of stage D patients. On the other hand, when the lymphoblastogenesis was performed in the presence of normal AB plasma, a partial restoration of lymphocyte function was noted, indicating the presence of a serum blocking factor in the blood of these patients. While there was no apparent decrease of B cell subpopulation, 57% of the tested patients showed significant reduction of T lymphocytes.