Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis
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《血管的通路杂志》
a Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, No. 201, Section 2, Shih-Pai Road, Taipei, Taiwan
b Division of Experimental Surgery, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan
c Department of Neurology, Taipei Veterans General Hospital and National Yang-Ming School of Medicine, Taipei, Taiwan
Abstract
Thymectomy is considered a therapeutic option for patients with myasthenia gravis. A myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after operation is still susceptible to a recurrence of myasthenic symptoms. To investigate which factors are related to relapse of symptoms in patients having thymectomy, we conduct a retrospective review in the patients who had experienced complete remission after thymectomy. Complete remission was achieved in 92 of 154 patients who received extended transsternal thymectomy for myasthenia gravis. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Multivariate Cox regression analysis revealed that thymoma was an independent factor for the development of relapse of symptoms. In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma.
Key Words: Myasthenia gravis; Thymectomy; Relapse
1. Introduction
The surgical removal of the thymus has become an accepted therapeutic option worldwide for myasthenia gravis (MG) since Blalock and coworkers first performed this procedure in 1936 and reported this technique in 1939 [1]. Factors that would affect the outcome of thymectomy have been investigated broadly [2–4]. It would seem as if a myasthenic patient could be considered improved or symptom-free without ever completely recovering. That is, a myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after the operation is still susceptible to a recurrence of myasthenic symptoms and signs. The reason for the recurrence of symptoms in myasthenic patients who had experienced complete remission after thymectomy remained undetermined. In this article, we conduct a retrospective review in the patients who had experienced complete remission after transsternal thymectomy to investigate which factors are related to relapse of symptoms in these patients during the postoperative period.
2. Patients and methods
2.1. Patients
From June 1986 to December 2001, 168 consecutive patients with MG underwent extended transsternal thymectomy in Taipei Veterans General Hospital. Indications for thymectomy in these patients included MG associated with coexistent thymoma and generalized MG with poor response of medical control. The operative approach was carried out by median sternotomy. The thymus along with the adjacent pericardial fat was freed from the pericardium and mediastinal pleura. The cervical extension of each lobe was easily removed with the body of the gland by gentle traction. All the patients with thymoma had postoperative radiation therapy except the patients with stage I. Complete resection of thymoma along with thymic gland was achieved in all patients with thymoma but two patients with stage III and IV who had incomplete resection. Of these 168 patients, 154 patients including 61 men and 93 women were available for follow-up evaluation (91.6%). Follow-up information was obtained by review of the hospital and clinic records and by telephone contact. The postoperative status of myasthenia gravis was assessed at the interval of 1, 3, 6 months and then annually. Complete remission was defined as no symptom or sign with no need of medication for at least 12 consecutive months according to the remission definition published by the MG Foundation of America (MGFA) [5]. Complete remission was achieved in 92 of these 154 patients (59.7%) during the follow-up period. For the other 62 patients who did not meet the criteria of complete remission, either myasthenic medications were always needed to control the symptoms after operation, or the period when the patients were free of symptoms with no need of medication were less than 12 consecutive months during the follow-up period. Relapse of symptoms was defined as recurrence of the myasthenic symptoms after complete remission was reached. These 92 patients were divided into two groups, thymomatous and nonthymomatous groups. The demographic data including sex, age, preoperative symptoms duration, preoperative MG type, preoperative steroid use and relapse of symptoms were reviewed. All the variables between these two groups of patients were compared.
2.2. Statistical analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS, ver. 12.0, Chicago, IL, USA). All continuous data are expressed as a mean± standard deviation. Categorical variables were analyzed by Fisher's exact test. Continuous variables were analyzed by as appropriate and by the Two-sample t-test or the Mann–Whitney U test. The events of symptom relapse in the patients who had complete remission during the follow-up period were calculated by the Kaplan–Meier method. The Log-rank test was used for the determination of statistical significance between variables. Multiple Cox regression analysis was also performed. P value less than 0.05 was considered to be significant.
3. Results
The demographic data of 92 patients in whom complete remission was achieved after thymectomy are shown in Table 1. The mean follow-up duration was 106.8±49.0 months (36 to 203 months). For patients without thymoma, the histological examination revealed normal thymic gland in 19 patients, hyperplasia in 49 patients and thymic cyst in 2 patients. For patients with thymoma, the histology of thymoma included lymphocyte predominant in 9 patients, mixed type in 9 patients, spindle cell predominant in 2 patients and epithelium predominant in 2 patients. The staging of the resected thymomas was stage I in 9 patients, stage II in 10 patients, stage III in 2 patients and stage IV in one patient. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). The recurrent myasthenic symptoms of these 20 patients were all mild. The medication for these patients to control the symptoms varied from anticholinesterase agents or steroid alone, to combination therapy including anticholinesterase agents, steroid, and azathioprine. Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Fig.1 shows the difference of the incidence of relapse in these two groups during the follow-up period. The duration from complete remission to relapse in the thymomatous group was significantly shorter than that in the nonthymomatous group (P=0.0001). Table 2 shows the results of comparison between the patients with and without relapse of symptoms after thymectomy. The difference of the preoperative steroid treatment between these two groups of patients was not significant. Ten of 20 patients with relapse of symptoms had thymoma (50%), while only 12 of 72 patients without relapse of symptoms had thymoma (16.7%). The difference was statistically significant (P=0.0001). Multivariate Cox regression analysis performed by entering some clinical factors including sex, age, MG severity, and symptom duration before surgery revealed that thymoma (odds ratio = 9.093, 95% C.I. of odds = (2.411–34.295)) was an independent factor for the development of relapse of symptoms (Table 3). In 10 patients with thymoma and relapse of symptoms, CT scan of chest was performed and it was found that 4 patients had tumor recurrence in the follow-up period. In these 4 patients with tumor recurrence, the postoperative stage was stage II in one patient, stage III in two patients and stage IV in one patient. Two of these 4 patients had incomplete resection in the original operation, one in stage III and one in stage IV, respectively.
4. Discussion
To evaluate the efficacy of thymectomy for myasthenia gravis, according to Jaretzki et al., exacerbations after remission in the follow-up period should be included in the paper, which is seldom discussed in the literature [6]. Actually a myasthenic patient would develop recurrence of symptoms even after stable complete remission has been achieved for years after operation as we observed in the clinical settings. For this reason, we conducted this study and found that thymoma was an adverse factor influencing the outcome of the patients who had experienced complete remission after thymectomy. The relapse rate in the thymomatous group was 45.5%, significantly higher than 14.3% in the nonthymomatous group. The relapse rate in our series is also much higher than a previous report by Jaretzki et al. in that only 2 of 65 patients (3%) without thymoma in remission experienced relapse of symptoms [7]. The operation they performed was en bloc transcervical-transsternal maximal thymectomy. The mean duration of follow-up in their study was only 40 months (6 to 89 months). We observed that higher relapse rate in our series may be associated with long follow-up duration of our patients (mean of 106.8 months). Would the different operative procedure performed in Jaretzki et al. and our series affect the relapse rate was unknown.
For patients having thymectomy for MG, Masaoka and coworkers concluded that absence of thymoma was one of the favorable prognostic factors [2]. Venuta et al. also found that the group of patients with thymoma presented a lower remission rate (14.5 vs. 29%) when compared with the non-thymomatous group [3]. Contrary to these reports, in the report by Perrot et al., the authors concluded that the presence of a thymoma should not necessarily be viewed as a negative prognostic factor in the patients with MG having thymectomy [4]. The relationship between the recurrence of thymoma and the relapse of MG symptoms was unclear. Gotti et al. reported that a patient with thymoma and MG in whom complete remission was achieved 6 months after thymectomy developed relapse of symptoms after 14 years of freedom from symptoms [8]. A second operation for the removal of the recurrent thymoma was performed. Evoli et al., in their study enrolling 207 myasthenic patients who were operated on for thymoma, suggested that recurrence of thymoma affected the course of MG differently [9]. In three of their patients, the onset of myasthenic symptoms occurred together with the first or even the second tumor recurrence. In the series by Haniuda et al., 24 patients with recurrence of thymoma were studied [10]. Thirteen of these 24 patients had MG before the original operation. The authors reported that the deterioration of the MG was associated with the development of tumor recurrence in 8 patients. In our study, we also found that four of 10 patients with thymoma and relapse of symptoms had tumor recurrence including 2 patients with incomplete resection. These two patients did achieve stable complete remission after postoperative radiation therapy in the postoperative period, however, then developed relapse of MG symptoms while tumor recurrence was noted. The reason for why the remaining 6 patients with thymoma but without tumor recurrence and the other 10 patients without thymoma had relapse of symptoms during the follow-up period was unknown. Could relapse of symptoms be due to occult tumor recurrence or metastasis that could not be found in the examinations Or it is because of incomplete removal of the thymus gland as some authors pointed out that recurrence of thymic hyperplasia or incomplete removal of the thymus may account for the poor postoperative response [11,12].
Some MG patients in remission would develop a recurrence of myasthenic signs under certain circumstances. In the study of Emeryk et al., they found that 17 of 20 MG patients in complete remission had abnormal single-fiber EMG, indicating that some subclinical disturbances of neuromuscular transmission existed in some MG patients [13]. Fifteen of these 20 patients had undergone thymectomy. They concluded that in the majority of patients with MG, the remissions are only apparently complete. Recently, Wakata et al. reported their experience in the management of the patients with relapse of ocular symptoms after remission of myasthenia gravis [14]. Eleven patients with relapse of ocular symptoms and 29 patients in complete remission without relapse were enrolled in their study. They found that early thymectomy and postoperative administration of prednisolone could lead to superior outcome in MG patients. In their study, contrary to our findings, 8 of 29 patients without relapse and none of 11 patients with relapse had thymoma. The follow-up duration was not mentioned in their study. In the report by Scoppetta et al., the results of electromyographic tests of repetitive supramaximal stimulation and the anti-acetylcholine receptor antibody were assessed in 10 patients who had thymectomy and seemed to recover from MG after operation [15]. Only two of these 10 patients had normal tests showing a lack of electromyographic myasthenia fatigability and the absence of circulating anti-AchR antibodies. The authors estimated that the risk of a recurrence of MG was lower in these two patients than in the others. The mean duration of complete remission in their study was 18.9 months (4 to 60 months). It seemed that sex, age, preoperative symptom duration, MG severity and preoperative steroid treatment did not affect the outcome of the patients who were in complete remission after operation in our study. The postoperative electromyographic test and anti-acetylcholine receptor antibody titer were not routinely checked in our patients.
In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma. Careful clinical survey to rule out tumor recurrence in MG patients with thymoma who experienced relapse of symptoms after thymectomy is warranted. Early relapse from complete remission is also observed in some MG patients with thymoma.
References
Blalock A, Mason MF, Morgan KJ, Riven SS. Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed. Ann Surg 1939; 110:544–561.
Masaoka A, Yamakawa Y, Niwa H, Fukai I, Kondo S, Kobayashi M, Fujii Y, Monden Y. Extended thymecotmy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg 1996; 62:853–859.
Venuta F, Rendina EA, Giacomo TD, Rocca GD, Antonini G, Ciccone AM, Ricci C, Coloni GF. Thymectomy for myasthenia gravis: a 27-year experience. Euro J Cardio Thorac Surg 1999; 15:621–625.
Perrot M, Liu J, Bril V, McRae K, Bezjak A, Keshavjee SH. Prognostic significance of thymomas in patients with myasthenia gravis. Ann Thorac Surg 2002; 74:1658–1662.
Jaretzki A III, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Myasthenia gravis: recommendations for clinical research standards. Ann Thorac Surg 2000; 70:327–334.
Jaretzki A III, Aarli JA, Kaminski HJ, Phillips LH, Sanders DB. Clinical research standards committee, medical/scientific advisory board, myasthenia gravis foundation of America, Inc. Thymectomy for myasthenia gravis: evaluation requires controlled prospective studies. Ann Thorac Surg 2003; 76:1–3.
Jaretzki A III, Penn AS, Younger DS, Wolf M, Olarte MR, Lovelace RE, Rowland LP. ‘Maximal’ thymectomy for myasthenia gravis. J Thorac Cardiovasc Surg 1988; 95:747–757.
Gotti G, Paladini P, Haid MM, Biagi G, Bisceglie MD, Gioni R, Ciacci G. Late recurrence of thymoma and myasthenia gravis. Scand J Thor Cardiovasc Surg 1995; 29:37–38.
Evoli A, Minisci C, Di Schino C, Marsili F, Punzi C, Batocchi AP, Tonali PA, Doglietto GB, Granone P, Trodella L, Cassano A, Lauriola L. Thymoma in patients with MG: characteristics and long-term outcome. Neurology 2002; 59:1844–1850.
Haniuda M, Kondo R, Numanami H, Makiuchi A, Machida E, Amano J. Recurrence of thymoma: clinicopathological feature, re-operation, and outcome. J Surg Oncol 2001; 78:183–188.
Joseph BS, Joens TR. Recurrence of nonneoplastic thymus after thymectomy for myasthenia gravis. Neurology 1973; 23:109–116.
Rosenberg M, Jauregui WO, Vega ME, Herrera MR, Roncoroni AJ, Rojas OR, Olmedo GSM. Recurrence of thymic hyperplasia after trans-sternal thymectomy in myasthenia gravis. Chest 1986; 89:888–889.
Emeryk B, Katazyna R, Nowak-Michalska T. Do true remissions in myasthenia really exist An electrophysiological study. J Neurol 1985; 231:331–335.
Wakata N, Iguchi H, Sugimoto H, Nomoto N, Kurihara T. Relapse of ocular symptoms after remission of myasthenia gravis. Clin Neurol Neurosurg 2003; 105:75–77.
Scopetta C, Bartoccioni E, David P, Flamini G, Lo Monaco M, Scuderi F, Tonali P. When is there a full recovery for a myasthenia gravis patient. J Neurol 1982; 227:61–65.(Han-Shui Hsu, Chien-Sheng)
b Division of Experimental Surgery, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan
c Department of Neurology, Taipei Veterans General Hospital and National Yang-Ming School of Medicine, Taipei, Taiwan
Abstract
Thymectomy is considered a therapeutic option for patients with myasthenia gravis. A myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after operation is still susceptible to a recurrence of myasthenic symptoms. To investigate which factors are related to relapse of symptoms in patients having thymectomy, we conduct a retrospective review in the patients who had experienced complete remission after thymectomy. Complete remission was achieved in 92 of 154 patients who received extended transsternal thymectomy for myasthenia gravis. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Multivariate Cox regression analysis revealed that thymoma was an independent factor for the development of relapse of symptoms. In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma.
Key Words: Myasthenia gravis; Thymectomy; Relapse
1. Introduction
The surgical removal of the thymus has become an accepted therapeutic option worldwide for myasthenia gravis (MG) since Blalock and coworkers first performed this procedure in 1936 and reported this technique in 1939 [1]. Factors that would affect the outcome of thymectomy have been investigated broadly [2–4]. It would seem as if a myasthenic patient could be considered improved or symptom-free without ever completely recovering. That is, a myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after the operation is still susceptible to a recurrence of myasthenic symptoms and signs. The reason for the recurrence of symptoms in myasthenic patients who had experienced complete remission after thymectomy remained undetermined. In this article, we conduct a retrospective review in the patients who had experienced complete remission after transsternal thymectomy to investigate which factors are related to relapse of symptoms in these patients during the postoperative period.
2. Patients and methods
2.1. Patients
From June 1986 to December 2001, 168 consecutive patients with MG underwent extended transsternal thymectomy in Taipei Veterans General Hospital. Indications for thymectomy in these patients included MG associated with coexistent thymoma and generalized MG with poor response of medical control. The operative approach was carried out by median sternotomy. The thymus along with the adjacent pericardial fat was freed from the pericardium and mediastinal pleura. The cervical extension of each lobe was easily removed with the body of the gland by gentle traction. All the patients with thymoma had postoperative radiation therapy except the patients with stage I. Complete resection of thymoma along with thymic gland was achieved in all patients with thymoma but two patients with stage III and IV who had incomplete resection. Of these 168 patients, 154 patients including 61 men and 93 women were available for follow-up evaluation (91.6%). Follow-up information was obtained by review of the hospital and clinic records and by telephone contact. The postoperative status of myasthenia gravis was assessed at the interval of 1, 3, 6 months and then annually. Complete remission was defined as no symptom or sign with no need of medication for at least 12 consecutive months according to the remission definition published by the MG Foundation of America (MGFA) [5]. Complete remission was achieved in 92 of these 154 patients (59.7%) during the follow-up period. For the other 62 patients who did not meet the criteria of complete remission, either myasthenic medications were always needed to control the symptoms after operation, or the period when the patients were free of symptoms with no need of medication were less than 12 consecutive months during the follow-up period. Relapse of symptoms was defined as recurrence of the myasthenic symptoms after complete remission was reached. These 92 patients were divided into two groups, thymomatous and nonthymomatous groups. The demographic data including sex, age, preoperative symptoms duration, preoperative MG type, preoperative steroid use and relapse of symptoms were reviewed. All the variables between these two groups of patients were compared.
2.2. Statistical analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS, ver. 12.0, Chicago, IL, USA). All continuous data are expressed as a mean± standard deviation. Categorical variables were analyzed by Fisher's exact test. Continuous variables were analyzed by as appropriate and by the Two-sample t-test or the Mann–Whitney U test. The events of symptom relapse in the patients who had complete remission during the follow-up period were calculated by the Kaplan–Meier method. The Log-rank test was used for the determination of statistical significance between variables. Multiple Cox regression analysis was also performed. P value less than 0.05 was considered to be significant.
3. Results
The demographic data of 92 patients in whom complete remission was achieved after thymectomy are shown in Table 1. The mean follow-up duration was 106.8±49.0 months (36 to 203 months). For patients without thymoma, the histological examination revealed normal thymic gland in 19 patients, hyperplasia in 49 patients and thymic cyst in 2 patients. For patients with thymoma, the histology of thymoma included lymphocyte predominant in 9 patients, mixed type in 9 patients, spindle cell predominant in 2 patients and epithelium predominant in 2 patients. The staging of the resected thymomas was stage I in 9 patients, stage II in 10 patients, stage III in 2 patients and stage IV in one patient. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). The recurrent myasthenic symptoms of these 20 patients were all mild. The medication for these patients to control the symptoms varied from anticholinesterase agents or steroid alone, to combination therapy including anticholinesterase agents, steroid, and azathioprine. Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Fig.1 shows the difference of the incidence of relapse in these two groups during the follow-up period. The duration from complete remission to relapse in the thymomatous group was significantly shorter than that in the nonthymomatous group (P=0.0001). Table 2 shows the results of comparison between the patients with and without relapse of symptoms after thymectomy. The difference of the preoperative steroid treatment between these two groups of patients was not significant. Ten of 20 patients with relapse of symptoms had thymoma (50%), while only 12 of 72 patients without relapse of symptoms had thymoma (16.7%). The difference was statistically significant (P=0.0001). Multivariate Cox regression analysis performed by entering some clinical factors including sex, age, MG severity, and symptom duration before surgery revealed that thymoma (odds ratio = 9.093, 95% C.I. of odds = (2.411–34.295)) was an independent factor for the development of relapse of symptoms (Table 3). In 10 patients with thymoma and relapse of symptoms, CT scan of chest was performed and it was found that 4 patients had tumor recurrence in the follow-up period. In these 4 patients with tumor recurrence, the postoperative stage was stage II in one patient, stage III in two patients and stage IV in one patient. Two of these 4 patients had incomplete resection in the original operation, one in stage III and one in stage IV, respectively.
4. Discussion
To evaluate the efficacy of thymectomy for myasthenia gravis, according to Jaretzki et al., exacerbations after remission in the follow-up period should be included in the paper, which is seldom discussed in the literature [6]. Actually a myasthenic patient would develop recurrence of symptoms even after stable complete remission has been achieved for years after operation as we observed in the clinical settings. For this reason, we conducted this study and found that thymoma was an adverse factor influencing the outcome of the patients who had experienced complete remission after thymectomy. The relapse rate in the thymomatous group was 45.5%, significantly higher than 14.3% in the nonthymomatous group. The relapse rate in our series is also much higher than a previous report by Jaretzki et al. in that only 2 of 65 patients (3%) without thymoma in remission experienced relapse of symptoms [7]. The operation they performed was en bloc transcervical-transsternal maximal thymectomy. The mean duration of follow-up in their study was only 40 months (6 to 89 months). We observed that higher relapse rate in our series may be associated with long follow-up duration of our patients (mean of 106.8 months). Would the different operative procedure performed in Jaretzki et al. and our series affect the relapse rate was unknown.
For patients having thymectomy for MG, Masaoka and coworkers concluded that absence of thymoma was one of the favorable prognostic factors [2]. Venuta et al. also found that the group of patients with thymoma presented a lower remission rate (14.5 vs. 29%) when compared with the non-thymomatous group [3]. Contrary to these reports, in the report by Perrot et al., the authors concluded that the presence of a thymoma should not necessarily be viewed as a negative prognostic factor in the patients with MG having thymectomy [4]. The relationship between the recurrence of thymoma and the relapse of MG symptoms was unclear. Gotti et al. reported that a patient with thymoma and MG in whom complete remission was achieved 6 months after thymectomy developed relapse of symptoms after 14 years of freedom from symptoms [8]. A second operation for the removal of the recurrent thymoma was performed. Evoli et al., in their study enrolling 207 myasthenic patients who were operated on for thymoma, suggested that recurrence of thymoma affected the course of MG differently [9]. In three of their patients, the onset of myasthenic symptoms occurred together with the first or even the second tumor recurrence. In the series by Haniuda et al., 24 patients with recurrence of thymoma were studied [10]. Thirteen of these 24 patients had MG before the original operation. The authors reported that the deterioration of the MG was associated with the development of tumor recurrence in 8 patients. In our study, we also found that four of 10 patients with thymoma and relapse of symptoms had tumor recurrence including 2 patients with incomplete resection. These two patients did achieve stable complete remission after postoperative radiation therapy in the postoperative period, however, then developed relapse of MG symptoms while tumor recurrence was noted. The reason for why the remaining 6 patients with thymoma but without tumor recurrence and the other 10 patients without thymoma had relapse of symptoms during the follow-up period was unknown. Could relapse of symptoms be due to occult tumor recurrence or metastasis that could not be found in the examinations Or it is because of incomplete removal of the thymus gland as some authors pointed out that recurrence of thymic hyperplasia or incomplete removal of the thymus may account for the poor postoperative response [11,12].
Some MG patients in remission would develop a recurrence of myasthenic signs under certain circumstances. In the study of Emeryk et al., they found that 17 of 20 MG patients in complete remission had abnormal single-fiber EMG, indicating that some subclinical disturbances of neuromuscular transmission existed in some MG patients [13]. Fifteen of these 20 patients had undergone thymectomy. They concluded that in the majority of patients with MG, the remissions are only apparently complete. Recently, Wakata et al. reported their experience in the management of the patients with relapse of ocular symptoms after remission of myasthenia gravis [14]. Eleven patients with relapse of ocular symptoms and 29 patients in complete remission without relapse were enrolled in their study. They found that early thymectomy and postoperative administration of prednisolone could lead to superior outcome in MG patients. In their study, contrary to our findings, 8 of 29 patients without relapse and none of 11 patients with relapse had thymoma. The follow-up duration was not mentioned in their study. In the report by Scoppetta et al., the results of electromyographic tests of repetitive supramaximal stimulation and the anti-acetylcholine receptor antibody were assessed in 10 patients who had thymectomy and seemed to recover from MG after operation [15]. Only two of these 10 patients had normal tests showing a lack of electromyographic myasthenia fatigability and the absence of circulating anti-AchR antibodies. The authors estimated that the risk of a recurrence of MG was lower in these two patients than in the others. The mean duration of complete remission in their study was 18.9 months (4 to 60 months). It seemed that sex, age, preoperative symptom duration, MG severity and preoperative steroid treatment did not affect the outcome of the patients who were in complete remission after operation in our study. The postoperative electromyographic test and anti-acetylcholine receptor antibody titer were not routinely checked in our patients.
In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma. Careful clinical survey to rule out tumor recurrence in MG patients with thymoma who experienced relapse of symptoms after thymectomy is warranted. Early relapse from complete remission is also observed in some MG patients with thymoma.
References
Blalock A, Mason MF, Morgan KJ, Riven SS. Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed. Ann Surg 1939; 110:544–561.
Masaoka A, Yamakawa Y, Niwa H, Fukai I, Kondo S, Kobayashi M, Fujii Y, Monden Y. Extended thymecotmy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg 1996; 62:853–859.
Venuta F, Rendina EA, Giacomo TD, Rocca GD, Antonini G, Ciccone AM, Ricci C, Coloni GF. Thymectomy for myasthenia gravis: a 27-year experience. Euro J Cardio Thorac Surg 1999; 15:621–625.
Perrot M, Liu J, Bril V, McRae K, Bezjak A, Keshavjee SH. Prognostic significance of thymomas in patients with myasthenia gravis. Ann Thorac Surg 2002; 74:1658–1662.
Jaretzki A III, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Myasthenia gravis: recommendations for clinical research standards. Ann Thorac Surg 2000; 70:327–334.
Jaretzki A III, Aarli JA, Kaminski HJ, Phillips LH, Sanders DB. Clinical research standards committee, medical/scientific advisory board, myasthenia gravis foundation of America, Inc. Thymectomy for myasthenia gravis: evaluation requires controlled prospective studies. Ann Thorac Surg 2003; 76:1–3.
Jaretzki A III, Penn AS, Younger DS, Wolf M, Olarte MR, Lovelace RE, Rowland LP. ‘Maximal’ thymectomy for myasthenia gravis. J Thorac Cardiovasc Surg 1988; 95:747–757.
Gotti G, Paladini P, Haid MM, Biagi G, Bisceglie MD, Gioni R, Ciacci G. Late recurrence of thymoma and myasthenia gravis. Scand J Thor Cardiovasc Surg 1995; 29:37–38.
Evoli A, Minisci C, Di Schino C, Marsili F, Punzi C, Batocchi AP, Tonali PA, Doglietto GB, Granone P, Trodella L, Cassano A, Lauriola L. Thymoma in patients with MG: characteristics and long-term outcome. Neurology 2002; 59:1844–1850.
Haniuda M, Kondo R, Numanami H, Makiuchi A, Machida E, Amano J. Recurrence of thymoma: clinicopathological feature, re-operation, and outcome. J Surg Oncol 2001; 78:183–188.
Joseph BS, Joens TR. Recurrence of nonneoplastic thymus after thymectomy for myasthenia gravis. Neurology 1973; 23:109–116.
Rosenberg M, Jauregui WO, Vega ME, Herrera MR, Roncoroni AJ, Rojas OR, Olmedo GSM. Recurrence of thymic hyperplasia after trans-sternal thymectomy in myasthenia gravis. Chest 1986; 89:888–889.
Emeryk B, Katazyna R, Nowak-Michalska T. Do true remissions in myasthenia really exist An electrophysiological study. J Neurol 1985; 231:331–335.
Wakata N, Iguchi H, Sugimoto H, Nomoto N, Kurihara T. Relapse of ocular symptoms after remission of myasthenia gravis. Clin Neurol Neurosurg 2003; 105:75–77.
Scopetta C, Bartoccioni E, David P, Flamini G, Lo Monaco M, Scuderi F, Tonali P. When is there a full recovery for a myasthenia gravis patient. J Neurol 1982; 227:61–65.(Han-Shui Hsu, Chien-Sheng)