THE NEUROLOGICAL OUTCOME OF PATIENTS WITH MYASTHENIA GRAVIS UNDERWENT THYMECTOMY VIA STERNOTOMY AND VIDEO ASSISTED THORACOSCOPIC SURGERY (VATS)

Aim. Thymectomy is accepted in surgical treatment of patients with myasthenia gravis (MG). Earlier thymectomy via sternotomy replaces video-assisted thoracoscopic surgery (VATS) as less invasive, last years. The aim of this study was by comparing the neurological outcome to make a conclusion regarding effectiveness and reliability of the two methods of surgical removal of the thymus in patients with MG. Material and methods . The study included 60 patients with MG who are underwent thymectomy at the beginning their treatment: 30 patients underwent thymectomy via sternotomy, and remaining 30 patients via VATS. In order to evaluate the effect of these two operation techniques we compared data related directly to the operation- the number of post-operative hospital days, the incidence of post-operative complications, as well as data related to the neurological monitoring of these patients: directly after the operation, after one year of surgery and up to three years after surgery. Results . Data related to the immediate postoperative period indicate significant shorter hospitalisation after the VATS thymectomy (p < 0,001), but percentage of postoperative complications in both groups was the same (p = 0.381). Clinical deterioration in the first year after operation showed a uniform distribution regardless of the type of performed operation (p = 0.470). Number of re-thymectomy in the group underwent thymectomy via sternotomy or via VATS is a borderline statistically significant (p= 0.054). Complete stable remission, as a criterion that the thymic tissue was removed in its entirety, was observed in about 11% underwent thymectomy. For other patients, clinical remission is maintained with anticholinesterase and immunosuppressive therapy. Conclusion . The shorter hospitalization time and faster postoperative recovery, with an equal clinical efficacy and aesthetic component favors the VATS thymectomy compared to thymectomy via sternotomy as more acceptable in the surgical treatment of patients with MG.

It is believed that the thymus is responsible for the initiation of the immunological processes which cause the occurrence of autoantibodies to the acetyl-choline receptor (AChR). Although the association with an anti-MG AChR antibodies by first noticed Lindstrom 1976 (9), the benefit of thymectomy in patients suffering from MG is observed much earlier, at the beginning of the last century. So the first thymectomy in patients with MG was done in 1911 by Ferdinand Sauerbruch by transcervical way, after the x-ray recording of the chest, which has seen increased thymic shadow, and after thymectomy recorded clinical recovery (10). Since transcervical thymectomy proved insufficient because the low visibility and was accompanied by a large number of residual thymic tissue which required re-thymectomy, quickly was replaced via sternotomy.  This study compared the results of patients with MG underwent thymectomy via sternotomy and video assisted thoracoscopic surgery (VATS). In relation to the way thymectomy we compared following parameters:

Material and methods
-age, gender, the length of hospitalization, incidence of complications and lethal outcomes immediately after thymectomy, incidence and treatment of postoperative exacerbations, frequency of re-thymectomy , the length of postoperative recovery The goal of thymectomy is complete removal of the thymus gland and mediastinal fat tissue which can be a source of ectopic thymic tissue, which is often not available modern diagnostics. As stable and complete remission is criterion that the thymic tissue was completely removed (17) we followed the postoperative outcome immediately after thymectomy, then one year after operation as well as for a period longer than one year (up to 3 years). In doing so, the clinical status of the patients was assessed by Oserman and Genkins-in (12).
In order to evaluate the effect of these two operation techniques we used to compare data Most of the variables were presented as frequency of certain categories, while statistical significance of differences was tested with the Chi square test.
In case of continuous data, variables were presented as mean value ± standard deviation (SD), minimal and maximal values. Kolmogorov-Smirnov test was used for evaluation of normal data distribution . According to the results of this test, statistical significance between groups was tested by t-test or alternatively by Mann-Whitney or Wilcoxon test.
All the analyses were estimated at p<0.05 level of statistical significance.

Results
As in the total population of our patients (43 women and 17 men), and in both groups With regard to the recommendation that thymectomy should be done when the patient is stable, patients achived clinical remission with medicaments first, and followed that thymectomy performed.
As the MG is heterogeneous disease, has not accepted a single standard in the treatment of this disease as the best for anyone with MG (14). Pyridostigmine whose initial therapy dose should be adjusted to the symptoms of the disease. Corticosteroids and immunosuppressive therapy are introduced when Pyridostigmine is not enough to achieve therapeutic goals (13,14). Under clinical remission considered a situation where the patient is disease-free , wherein they may have some weakness in the closure of the eyes but without any other weakness of the muscle (14).
In the postoperative period, the dosages of corticosteroid was carefully reduced because any reduction of the dose of the drug carries a risk of relapse. Non-steroidal immunosuppressive drugs were added when corticosteroid therapy was not enough or when you want to avoid its adverse effects. Of non-steroidal immunosuppressive drugs, according to the consensus of experts, Azathioprine is in the first place for the treatment of MG which is respected in group of our patients, who are well tolerated and without any side effects from the therapy with Azathioprine (13,14).The deterioration of their condition is most frequently occurred in the abrupt reduction in therapy, due to an infection or due to residual thymic tissue. Therefore, clinical deterioration was the indication of the control scener of the chest: in 3 of the patients seen rest of thymic tissue, which is an indication for reoperation (Graphic 1.) All 3 reoperated patients were operated via sternotomy previously. Among our patients one was seronegative; he treated by VATS, and in this patient was seen thymic hyperplasia.
Pathohistological type of thymus was almost uniform in the group of patients operated via sternotomy and thus patients operated via VATS (P = 0.896).
A total of 5 patients was found atrophy of the thymus. The average age of these patients was 67.60 ± 6,986; and it was statistically significant difference as compared to patients with thymic hyperplasia and thymoma (p < 0,001).

Discussion
Thymectomy is an option which can minimize or even avoid immunosuppressive therapy in seropositive generalized myasthenia (18). It is suggested in younger than 45 years of age, with the advice to be done as soon as possible, because then the better the results of treatment (19).
Younger patients with a less severe and shorter duration of the disease, more likely have a complete remission after thymectomy (1).
Thymectomy is done in seronegative generalized MG patients also, when there is weak and uncertain response to immunosuppressive therapy (14).
If the patient does not respond or has insecurely course to immunosuppressive therapy or there is side-effects after it`s initiation, thymectomy is the method of choice in the elderly patient, also. As we followed this recommendation, the average age of our patients was 41,67±13,902 years.
All MG patients with thymoma should be operated (14).
Women were dominant in our group of operated patients, corresponding data from the literature where a higher incidence of women in the MG early onset (before the age of 50), in which thymectomy and primarily indicated (5). One of them is shown significantly more likely achieved clinical remission after thymectomy than without the operation (20% vs. 10%) (6).
In our group of a total of 60 patients is noted significant improvement in the clinical picture of patients directly after thymectomy (p = 0.01).
Effect of thymectomy in different decades in the period from 1940. to 2000. was followed by the another large study (6)  Thymoma is seen in 10 to 15% of cases (10), usually between 45 and 55 years of age, which corresponds to our results because in one patient in both groups, thymoma was found.
Comparing the effects of thymectomy via sternotomy or via VATS most commonly observed parameter directly related to the operation such as the duration of the operation, intraoperative blood loss, the perception of pain, duration of hospitalization, the need for artificial respiration, post-operative complications resulting in death (16,3) where it gives a certain advantage to thymectomy via VATS due to shorter hospitalization, a minor loss of blood and to better cosmetic effect. A meta-analysis of 12 studies that dealt with this problem gives also the advantage VATS thymectomy because fewer post-operative complications and and less frequency of myasthenic crisis (17).
Similar data were obtained in our group of patients: significantly longer hospitalization after sternothomy (p < 0,001), one death in the group operated via sternothomy which did not come out statistically significant while myasthenic crisis and pneumonia, which is often referred as post-operative complications in the literature, not observed among our patients (17).
The incomplete removal of the thymus leads to an unstable postoperative course while a complete stable remission is criteria that the thymic tissue was removed in its entirety (17).
13 Therefore, apart results related directly to the operation, we followed our clinical status of patients immediately after surgery, then after one year and 3 years of operations.
Immediate post-operative recovery was statistically significant (p = 0.002), and both operational techniques were equally effective (p = 0.762).
Number of clinical deterioration in the first year of operation showed that there is a homogeneous distribution of deterioration regardless of the type of surgery (p = 0.470). In 3 patients the cause of deterioration was rest of thymic tissue, which is an indication for rethymectomy.
All 3 patients who have need for re-thymectomy, were previously operated by sternothomy. This difference in the number of re-thymectomy between patients treated by various techniques was statistically significant (p = 0.054).
Other exacerbation was solved by correcting anticholinesterase therapy and corticosteroids, introduction azathioprine and series of PE.
It was concluded, that there were no statistically significant differences (p=0,325), in the treatment of deterioration in the patients operated by various techniques.
Three years after surgery, two patients in both operated group (around 11%) were in complete clinical remission: symptom-free and without treatment for a period longer than one year (8). Other patients were on combination anticholinesterase therapy and immunosuppressives , and none of them had need for PE. Types of treatment after 3 years of operation is not significantly different in patients operated by a variety of techniques (P = 0.358).

Conclusion
It can be concluded that the sternothomy and VATS thymectomy achieve equal clinical results, but shorter hospitalisations, and better cosmetic effect favored VATS as it is now more acceptable technique for thymectomy in patients with MG.