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Long-term effects of infrasternal mediastinoscopic thymectomy in myasthenia gravis
Journal of the Neurological Sciences 287 (2009) 185–187
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Long-term effects of infrasternal mediastinoscopic thymectomy in myasthenia gravis Hiroyuki Murai a,⁎, Akihiko Uchiyama b,1, Feng-Jun Mei a, Masayuki Kojima b, Jun-ichi Kira a a b
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
a r t i c l e
i n f o
Article history: Received 3 September 2008 Received in revised form 31 July 2009 Accepted 3 August 2009 Available online 2 September 2009 Keywords: Myasthenia gravis Endoscopic surgery Infrasternal mediastinoscopic thymectomy
a b s t r a c t Background: Endoscopic thymectomy is commonly used for treatment of myasthenia gravis (MG) patients due to its relatively low invasiveness. However, the long-term effects of endoscopic thymectomy have not been fully evaluated. Objective: To assess the long-term effects of extended infrasternal mediastinoscopic thymectomy (IMT) in MG patients and compare them with those of extended transsternal thymectomy (TT). Methods: Among 24 MG patients without thymoma who underwent thymectomy in our Institute between January 1997 and December 2000, 14 patients who received IMT and 10 who received TT were enrolled in the present study. Quantitative myasthenia gravis (QMG) score and anti-acetylcholine receptor antibody (antiAChR) titers were evaluated before and at five years after surgery. Results: After five years, QMG scores were reduced from 6.6 to 1.8 (p b 0.01) in the IMT group, and from 7.6 to 2.7 (p b 0.01) in the TT group. The anti-AChR titers were reduced from 75.2 to 40.1 (p = 0.027) in the IMT group, and from 224 to 61.3 (p = 0.020) in the TT group. Conclusion: These data suggest that the long-term therapeutic effect of IMT is equivalent to TT, and is thus suitable for the treatment of MG patients. © 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Materials and methods
Extended transsternal thymectomy (TT) is a well established procedure used for the treatment of myasthenia gravis (MG) [1,2]. Recent progress in video-assisted thoracoscopic surgery has allowed less invasive thymectomy [3–5], and its short-term prognosis has been reported [6]. This procedure does not require sternotomy, and thus has cosmetic advantages, as well as less morbidity and mortality. Infrasternal mediastinoscopic thymectomy (IMT) was first reported as an alternative to thoracoscopic surgery [7]. In addition to the advantages indicated for thoracoscopic thymectomy, IMT does not require one-lung ventilation. There is some controversy over the use of IMT due to its potential for failing to completely remove adipose tissue embedded in thymus tissues. We previously reported the short-term effect of IMT on MG patients [8], but the long-term outcomes and immunological effects have not been reported. Thus, in the present study we examined the long-term effects of IMT versus TT in MG patients without thymoma.
2.1. Patients Forty-one consecutive MG patients who received thymectomy between January 1997 and December 2000 in Kyushu University were retrospectively analyzed. We had been performing conventional TT, MGFA thymectomy classification T-3b [9], until late 1998, when we introduced the new IMT technique. Patients operated before November 1998 were assigned to the TT group, while those after December 1998 to the IMT group. Of note, other conditions including thymoma size or the status of invasion to adjacent organs altered the selection procedure. Of the 41 patients, 10 were excluded because of thymoma, five dropped out from the follow-up as they moved districts, and two died of cancer. The remaining 24 patients were followed up for more than five years; of these, 14 received IMT and 10 received TT. One patient who was initially scheduled to receive IMT required sternotomy during the operation due to insufficient lifting of the sternum, and was included in the TT group. The demographic features of the patients can be seen in Table 1. 2.2. Surgical techniques
⁎ Corresponding author. Department of Neurology, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka 820-8505, Japan. Tel.: +81 948 22 3800; fax: +81 948 29 5744. E-mail address: [email protected] (H. Murai). 1 Present address: Department of Surgery, Kyushu Kosei Nenkin Hospital, 1-8-1 Kishinoura, Yahatanishi-ku, Kitakyushu 806-8501, Japan. 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.08.002
The IMT procedures for MG patients were described previously [8,10]. Briefly, patients were placed in the supine position, and an arcshaped or longitudinal 4 cm incision was made just below the xiphoid process. In the first several cases, a 3 cm transverse incision was also made above the sternal notch to free the upper portion of the thymus.
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H. Murai et al. / Journal of the Neurological Sciences 287 (2009) 185–187
Table 1 Demographic features of IMT and TT patients.
Number of patients Age at operation (mean, range) Sex (female %) History of crisis (number, %) Additional treatments Cholinesterase (number, %) Corticosteroids (number, %) Maximal dose per day (mg) Duration of maximal dose (days) Immunosuppressants (number, %) Plasmapheresis (number, %) Baseline QMG score Baseline anti-AChR antibodies (nmol/l) Pathology of thymus Weight of removed thymus Hyperplasia (number, %)
IMT
TT
14 42.0 (22–73) 64.3 1 (7.1)
10 45.9 (16–69) 80.0 1 (10.0)
14 (100) 10 (71.4) 52.5 ± 4.9 43.2 ± 9.2
10 (100) 7 (70.0) 52.9 ± 7.0 42.3 ± 9.9
3 (21.4)
2 (20.0)
2 (14.3) 6.6 ± 3.2 (4–16) 75.2 ± 144 (0–527)
1 (10.0) 7.6 ± 2.9 (4–14) 224 ± 419 (0–1200)
99.1 ± 65.4 (10–200) 5 (35.7)
101.5 ± 44.0 (50–165) 3 (30.0)
Laparofan (Origin Medsystems, Menlo Park, CA, USA) was inserted beneath the sternum, and the sternum was lifted using Laparolift (Origin Medsystems). A 30° angled telescope was inserted through a trocar placed right below the incision. Instruments were then inserted through the incision. The anterior mediastinal tissue, including the thymus, was dissected free from the pericardium. The upper portion of the thymus was dissected free from the thyroid gland. After dividing the blood vessels, the thymus together with adipose tissue and thymoma, if any, was removed through the abdominal incision.
165 g) (Table 1). Histopathological findings of the removed thymus were hyperplasia in 5/14 (35.7%) in the IMT group and in 3/10 (30.0%) in the TT group. 3.2. Clinical improvement assessed by QMG score In the IMT group, the QMG score significantly decreased from 6.6 ± 3.2 (range 4–16) before the operation to 1.8 ± 2.1 (range 0–7) at N5 years after the operation (p b 0.001; Fig. 1A). In the TT group, the QMG score significantly decreased from 7.6± 2.9 (range 4–14) before the operation to 2.7 ± 1.8 (range 0–5) at N5 years after the operation (p b 0.001) (Fig. 1B). 3.3. MGFA post-intervention status Three patients (21.4%) in the IMT group and two patients (20.0%) in the TT group achieved Complete Stable Remission (CSR) of MGFA post-intervention status at N5 years after surgery; there was no difference between the groups (p = 0.932). 3.4. Anti-AChR antibody titer measurement In the IMT group, the anti-AChR antibody titer decreased significantly from 75.2 ± 144 (range 0–527) before the operation to 40.1 ± 80.6 (range 0–269) at N5 years after the operation (p = 0.027) (Fig. 1C). In the TT group, the anti-AChR antibody titer decreased significantly from 224 ± 419 (range 0–1200) before the operation to 61.3 ± 95.9 (range 0–822) at N5 years after the operation (p = 0.020) (Fig. 1D). 4. Discussion
2.3. Long-term effects of IMT and TT The average period from operation to the date of evaluation was 87.5 ± 13.2 months (mean ± SD, range 67–111) in total, 79.1 ± 7.3 months (mean±SD, range 67–89) in the IMT group, and 99.2± 10.2 months (mean ±SD, range 81–111) in the TT group. To assess clinical improvement, we applied quantitative MG score (QMG score) [9] before and at N5 years after surgery. Briefly, the degree of ptosis, diplopia, facial muscle strength, ability to speak and swallow, neck muscle strength, vital capacity, and strength of upper and lower extremities were graded on a scale of 0 to 3, with 0 representing normal and 3 maximal weakness. The score for each item was summed to determine the patients' QMG score. Clinical evaluation was performed by one of two board qualified expert neurologists at the time when symptoms were worst during the day. No patients had received immunomodulatory therapy at the time of the initial QMG score. Anti-acetylcholine receptor (AChR) antibody levels were also examined by radioimmunoassay before and at N5 years after surgery. 2.4. Statistical analysis The nonparametric Wilcoxon signed rank test was used to determine significant changes in QMG scores and titers of anti-AChR antibody. Mann–Whitney's U Test was used to compare the weight of removed thymic tissues. Chi-square test for independence was used to compare the frequency of patients achieving MGFA Complete Stable Remission. pb 0.05 was considered statistically significant. Data are presented as mean±SD. 3. Results 3.1. Pathological findings in surgical specimens There was no difference in the net weights of thymic tissue taken from operated MG patients in the IMT group (99.1 ± 65.4 g, range 10–200 g) compared with the TT group (101.5± 44.0 g, range 50–
Although the therapeutic efficacy of thymectomy in non-thymomatous MG patients is controversial [11], thymectomy is still widely used for treatment of MG. In the present study, we demonstrated that the long-term efficacy of IMT was equivalent to TT, as shown by the significant reduction in QMG scores at N5 years after operation with both procedures. Similarly, anti-AChR antibody levels were also significantly reduced in both procedures. Although it would have been more informative to combine the thymoma associated MG patients with the non-thymoma patients, the thymoma cases were removed as these two groups were not clinically identical; i.e., more thymoma cases would be included in the TT group. Furthermore, by eliminating the thymoma associated MG cases, the two groups had very similar clinical profiles, including the usage of corticosteroids and other immunosuppressants (Table 1). The net weight of the removed thymus did not differ between the two groups, indicating that complete removal of the thymus was achieved in both procedures. In the first few cases in the IMT group, a transverse cervical incision was made to ensure no remaining thymus tissue. However, this procedure was discontinued as the visual field was large enough without the cervical incision, and surgeons felt confident about completely removing the thymus without adding this procedure. There are several limitations of the present study. First, this was a retrospective examination of a relatively small number of patients. Second, we eliminated the thymoma patients as IMT cannot be used to manage cases accompanied by large-sized or invasive thymomas, and as such, the two groups would not have contained the same proportion of thymoma patients. Third, it is unlikely that clinical improvement is solely the result of thymectomy alone as immunomodulatory treatment was used in many cases after surgery. However, as shown in Table 1, the additional treatments in both groups were identical. Furthermore, the level of clinical improvement observed in the limited number of cases who did not receive steroids suggests an efficacy of the surgery itself. Although IMT has a number of advantages over TT including low invasiveness without sternotomy, cosmetic merit, and less morbidity
H. Murai et al. / Journal of the Neurological Sciences 287 (2009) 185–187
187
Fig. 1. Changes in QMG scores and anti-AChR antibody titers after thymectomy. Both the IMT group (A) and the TT group (B) showed a significant reduction in QMG scores. Similarly, both the IMT group (C) and the TT group (D) showed a significant decrease in anti-AChR antibody titers.
and mortality, there are a number of potential disadvantages. First, IMT has a longer operation time than TT, especially when surgeons have little practice, although this can be reduced with experience. Second, IMT requires Laparolift equipment to lift the sternum, although if this device is unavailable, then vascular tape, a device used to lift up vessels during vascular surgery, can be used. Third, IMT cannot be used in cases associated with invasive thymomas when invasion of the lung or pericardium is severe; TT is recommended in such cases. In summary, we showed that the long-term management of MG using IMT is equivalent to that using TT. Since IMT it is less invasive than TT, and also has cosmetic advantages, IMT is a promising procedure for the treatment of the majority of MG patients who require thymectomy. Prospective studies with increased number of patients will form the basis of future work. Acknowledgment This work was supported in part by a Neuroimmunological Disease Research Committee grant from the Ministry of Health, Labor and Welfare, Japan. References [1] Jaretzki III A, Wolff M. “Maximal” thymectomy for myasthenia gravis. Surgical anatomy and operative technique. J Thorac Cardiovasc Surg 1988;96:711–6.
[2] Masaoka A, Yamakawa Y, Niwa H, Fukai I, Kondo S, Kobayashi M, et al. Extended thymectomy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg 1996;62:853–9. [3] Yim AP, Kay RL, Ho JK. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest 1995;108:1440–3. [4] Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR, Scruggs GR. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg 1996;112:1352–9 discussion 1359–1360. [5] Ruckert JC, Gellert K, Muller JM. Operative technique for thoracoscopic thymectomy. Surg Endosc 1999;13:943–6. [6] Mantegazza R, Confalonieri P, Antozzi C, Novellino L, Ferro MT, Porta M, et al. Video-assisted thoracoscopic extended thymectomy (VATET) in myasthenia gravis. Two-year follow-up in 101 patients and comparison with the transsternal approach. Ann N Y Acad Sci 1998;841:749–52. [7] Kido T, Hazama K, Inoue Y, Tanaka Y, Takao T. Resection of anterior mediastinal masses through an infrasternal approach. Ann Thorac Surg 1999;67:263–5. [8] Uchiyama A, Shimizu S, Murai H, Kuroki S, Okido M, Tanaka M. Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients. Ann Thorac Surg 2001;72:1902–5. [9] Jaretzki III A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Neurology 2000;55:16–23. [10] Uchiyama A, Shimizu S, Murai H, Ohshima A, Konomi H, Ogura Y, et al. Infrasternal mediastinoscopic surgery for anterior mediastinal masses. Surg Endosc 2004;18:843–6. [11] Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:7–15.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Long-term effects of infrasternal mediastinoscopic thymectomy in myasthenia gravis Hiroyuki Murai a,⁎, Akihiko Uchiyama b,1, Feng-Jun Mei a, Masayuki Kojima b, Jun-ichi Kira a a b
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
a r t i c l e
i n f o
Article history: Received 3 September 2008 Received in revised form 31 July 2009 Accepted 3 August 2009 Available online 2 September 2009 Keywords: Myasthenia gravis Endoscopic surgery Infrasternal mediastinoscopic thymectomy
a b s t r a c t Background: Endoscopic thymectomy is commonly used for treatment of myasthenia gravis (MG) patients due to its relatively low invasiveness. However, the long-term effects of endoscopic thymectomy have not been fully evaluated. Objective: To assess the long-term effects of extended infrasternal mediastinoscopic thymectomy (IMT) in MG patients and compare them with those of extended transsternal thymectomy (TT). Methods: Among 24 MG patients without thymoma who underwent thymectomy in our Institute between January 1997 and December 2000, 14 patients who received IMT and 10 who received TT were enrolled in the present study. Quantitative myasthenia gravis (QMG) score and anti-acetylcholine receptor antibody (antiAChR) titers were evaluated before and at five years after surgery. Results: After five years, QMG scores were reduced from 6.6 to 1.8 (p b 0.01) in the IMT group, and from 7.6 to 2.7 (p b 0.01) in the TT group. The anti-AChR titers were reduced from 75.2 to 40.1 (p = 0.027) in the IMT group, and from 224 to 61.3 (p = 0.020) in the TT group. Conclusion: These data suggest that the long-term therapeutic effect of IMT is equivalent to TT, and is thus suitable for the treatment of MG patients. © 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Materials and methods
Extended transsternal thymectomy (TT) is a well established procedure used for the treatment of myasthenia gravis (MG) [1,2]. Recent progress in video-assisted thoracoscopic surgery has allowed less invasive thymectomy [3–5], and its short-term prognosis has been reported [6]. This procedure does not require sternotomy, and thus has cosmetic advantages, as well as less morbidity and mortality. Infrasternal mediastinoscopic thymectomy (IMT) was first reported as an alternative to thoracoscopic surgery [7]. In addition to the advantages indicated for thoracoscopic thymectomy, IMT does not require one-lung ventilation. There is some controversy over the use of IMT due to its potential for failing to completely remove adipose tissue embedded in thymus tissues. We previously reported the short-term effect of IMT on MG patients [8], but the long-term outcomes and immunological effects have not been reported. Thus, in the present study we examined the long-term effects of IMT versus TT in MG patients without thymoma.
2.1. Patients Forty-one consecutive MG patients who received thymectomy between January 1997 and December 2000 in Kyushu University were retrospectively analyzed. We had been performing conventional TT, MGFA thymectomy classification T-3b [9], until late 1998, when we introduced the new IMT technique. Patients operated before November 1998 were assigned to the TT group, while those after December 1998 to the IMT group. Of note, other conditions including thymoma size or the status of invasion to adjacent organs altered the selection procedure. Of the 41 patients, 10 were excluded because of thymoma, five dropped out from the follow-up as they moved districts, and two died of cancer. The remaining 24 patients were followed up for more than five years; of these, 14 received IMT and 10 received TT. One patient who was initially scheduled to receive IMT required sternotomy during the operation due to insufficient lifting of the sternum, and was included in the TT group. The demographic features of the patients can be seen in Table 1. 2.2. Surgical techniques
⁎ Corresponding author. Department of Neurology, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka 820-8505, Japan. Tel.: +81 948 22 3800; fax: +81 948 29 5744. E-mail address: [email protected] (H. Murai). 1 Present address: Department of Surgery, Kyushu Kosei Nenkin Hospital, 1-8-1 Kishinoura, Yahatanishi-ku, Kitakyushu 806-8501, Japan. 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.08.002
The IMT procedures for MG patients were described previously [8,10]. Briefly, patients were placed in the supine position, and an arcshaped or longitudinal 4 cm incision was made just below the xiphoid process. In the first several cases, a 3 cm transverse incision was also made above the sternal notch to free the upper portion of the thymus.
186
H. Murai et al. / Journal of the Neurological Sciences 287 (2009) 185–187
Table 1 Demographic features of IMT and TT patients.
Number of patients Age at operation (mean, range) Sex (female %) History of crisis (number, %) Additional treatments Cholinesterase (number, %) Corticosteroids (number, %) Maximal dose per day (mg) Duration of maximal dose (days) Immunosuppressants (number, %) Plasmapheresis (number, %) Baseline QMG score Baseline anti-AChR antibodies (nmol/l) Pathology of thymus Weight of removed thymus Hyperplasia (number, %)
IMT
TT
14 42.0 (22–73) 64.3 1 (7.1)
10 45.9 (16–69) 80.0 1 (10.0)
14 (100) 10 (71.4) 52.5 ± 4.9 43.2 ± 9.2
10 (100) 7 (70.0) 52.9 ± 7.0 42.3 ± 9.9
3 (21.4)
2 (20.0)
2 (14.3) 6.6 ± 3.2 (4–16) 75.2 ± 144 (0–527)
1 (10.0) 7.6 ± 2.9 (4–14) 224 ± 419 (0–1200)
99.1 ± 65.4 (10–200) 5 (35.7)
101.5 ± 44.0 (50–165) 3 (30.0)
Laparofan (Origin Medsystems, Menlo Park, CA, USA) was inserted beneath the sternum, and the sternum was lifted using Laparolift (Origin Medsystems). A 30° angled telescope was inserted through a trocar placed right below the incision. Instruments were then inserted through the incision. The anterior mediastinal tissue, including the thymus, was dissected free from the pericardium. The upper portion of the thymus was dissected free from the thyroid gland. After dividing the blood vessels, the thymus together with adipose tissue and thymoma, if any, was removed through the abdominal incision.
165 g) (Table 1). Histopathological findings of the removed thymus were hyperplasia in 5/14 (35.7%) in the IMT group and in 3/10 (30.0%) in the TT group. 3.2. Clinical improvement assessed by QMG score In the IMT group, the QMG score significantly decreased from 6.6 ± 3.2 (range 4–16) before the operation to 1.8 ± 2.1 (range 0–7) at N5 years after the operation (p b 0.001; Fig. 1A). In the TT group, the QMG score significantly decreased from 7.6± 2.9 (range 4–14) before the operation to 2.7 ± 1.8 (range 0–5) at N5 years after the operation (p b 0.001) (Fig. 1B). 3.3. MGFA post-intervention status Three patients (21.4%) in the IMT group and two patients (20.0%) in the TT group achieved Complete Stable Remission (CSR) of MGFA post-intervention status at N5 years after surgery; there was no difference between the groups (p = 0.932). 3.4. Anti-AChR antibody titer measurement In the IMT group, the anti-AChR antibody titer decreased significantly from 75.2 ± 144 (range 0–527) before the operation to 40.1 ± 80.6 (range 0–269) at N5 years after the operation (p = 0.027) (Fig. 1C). In the TT group, the anti-AChR antibody titer decreased significantly from 224 ± 419 (range 0–1200) before the operation to 61.3 ± 95.9 (range 0–822) at N5 years after the operation (p = 0.020) (Fig. 1D). 4. Discussion
2.3. Long-term effects of IMT and TT The average period from operation to the date of evaluation was 87.5 ± 13.2 months (mean ± SD, range 67–111) in total, 79.1 ± 7.3 months (mean±SD, range 67–89) in the IMT group, and 99.2± 10.2 months (mean ±SD, range 81–111) in the TT group. To assess clinical improvement, we applied quantitative MG score (QMG score) [9] before and at N5 years after surgery. Briefly, the degree of ptosis, diplopia, facial muscle strength, ability to speak and swallow, neck muscle strength, vital capacity, and strength of upper and lower extremities were graded on a scale of 0 to 3, with 0 representing normal and 3 maximal weakness. The score for each item was summed to determine the patients' QMG score. Clinical evaluation was performed by one of two board qualified expert neurologists at the time when symptoms were worst during the day. No patients had received immunomodulatory therapy at the time of the initial QMG score. Anti-acetylcholine receptor (AChR) antibody levels were also examined by radioimmunoassay before and at N5 years after surgery. 2.4. Statistical analysis The nonparametric Wilcoxon signed rank test was used to determine significant changes in QMG scores and titers of anti-AChR antibody. Mann–Whitney's U Test was used to compare the weight of removed thymic tissues. Chi-square test for independence was used to compare the frequency of patients achieving MGFA Complete Stable Remission. pb 0.05 was considered statistically significant. Data are presented as mean±SD. 3. Results 3.1. Pathological findings in surgical specimens There was no difference in the net weights of thymic tissue taken from operated MG patients in the IMT group (99.1 ± 65.4 g, range 10–200 g) compared with the TT group (101.5± 44.0 g, range 50–
Although the therapeutic efficacy of thymectomy in non-thymomatous MG patients is controversial [11], thymectomy is still widely used for treatment of MG. In the present study, we demonstrated that the long-term efficacy of IMT was equivalent to TT, as shown by the significant reduction in QMG scores at N5 years after operation with both procedures. Similarly, anti-AChR antibody levels were also significantly reduced in both procedures. Although it would have been more informative to combine the thymoma associated MG patients with the non-thymoma patients, the thymoma cases were removed as these two groups were not clinically identical; i.e., more thymoma cases would be included in the TT group. Furthermore, by eliminating the thymoma associated MG cases, the two groups had very similar clinical profiles, including the usage of corticosteroids and other immunosuppressants (Table 1). The net weight of the removed thymus did not differ between the two groups, indicating that complete removal of the thymus was achieved in both procedures. In the first few cases in the IMT group, a transverse cervical incision was made to ensure no remaining thymus tissue. However, this procedure was discontinued as the visual field was large enough without the cervical incision, and surgeons felt confident about completely removing the thymus without adding this procedure. There are several limitations of the present study. First, this was a retrospective examination of a relatively small number of patients. Second, we eliminated the thymoma patients as IMT cannot be used to manage cases accompanied by large-sized or invasive thymomas, and as such, the two groups would not have contained the same proportion of thymoma patients. Third, it is unlikely that clinical improvement is solely the result of thymectomy alone as immunomodulatory treatment was used in many cases after surgery. However, as shown in Table 1, the additional treatments in both groups were identical. Furthermore, the level of clinical improvement observed in the limited number of cases who did not receive steroids suggests an efficacy of the surgery itself. Although IMT has a number of advantages over TT including low invasiveness without sternotomy, cosmetic merit, and less morbidity
H. Murai et al. / Journal of the Neurological Sciences 287 (2009) 185–187
187
Fig. 1. Changes in QMG scores and anti-AChR antibody titers after thymectomy. Both the IMT group (A) and the TT group (B) showed a significant reduction in QMG scores. Similarly, both the IMT group (C) and the TT group (D) showed a significant decrease in anti-AChR antibody titers.
and mortality, there are a number of potential disadvantages. First, IMT has a longer operation time than TT, especially when surgeons have little practice, although this can be reduced with experience. Second, IMT requires Laparolift equipment to lift the sternum, although if this device is unavailable, then vascular tape, a device used to lift up vessels during vascular surgery, can be used. Third, IMT cannot be used in cases associated with invasive thymomas when invasion of the lung or pericardium is severe; TT is recommended in such cases. In summary, we showed that the long-term management of MG using IMT is equivalent to that using TT. Since IMT it is less invasive than TT, and also has cosmetic advantages, IMT is a promising procedure for the treatment of the majority of MG patients who require thymectomy. Prospective studies with increased number of patients will form the basis of future work. Acknowledgment This work was supported in part by a Neuroimmunological Disease Research Committee grant from the Ministry of Health, Labor and Welfare, Japan. References [1] Jaretzki III A, Wolff M. “Maximal” thymectomy for myasthenia gravis. Surgical anatomy and operative technique. J Thorac Cardiovasc Surg 1988;96:711–6.
[2] Masaoka A, Yamakawa Y, Niwa H, Fukai I, Kondo S, Kobayashi M, et al. Extended thymectomy for myasthenia gravis patients: a 20-year review. Ann Thorac Surg 1996;62:853–9. [3] Yim AP, Kay RL, Ho JK. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Chest 1995;108:1440–3. [4] Mack MJ, Landreneau RJ, Yim AP, Hazelrigg SR, Scruggs GR. Results of video-assisted thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg 1996;112:1352–9 discussion 1359–1360. [5] Ruckert JC, Gellert K, Muller JM. Operative technique for thoracoscopic thymectomy. Surg Endosc 1999;13:943–6. [6] Mantegazza R, Confalonieri P, Antozzi C, Novellino L, Ferro MT, Porta M, et al. Video-assisted thoracoscopic extended thymectomy (VATET) in myasthenia gravis. Two-year follow-up in 101 patients and comparison with the transsternal approach. Ann N Y Acad Sci 1998;841:749–52. [7] Kido T, Hazama K, Inoue Y, Tanaka Y, Takao T. Resection of anterior mediastinal masses through an infrasternal approach. Ann Thorac Surg 1999;67:263–5. [8] Uchiyama A, Shimizu S, Murai H, Kuroki S, Okido M, Tanaka M. Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients. Ann Thorac Surg 2001;72:1902–5. [9] Jaretzki III A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America. Neurology 2000;55:16–23. [10] Uchiyama A, Shimizu S, Murai H, Ohshima A, Konomi H, Ogura Y, et al. Infrasternal mediastinoscopic surgery for anterior mediastinal masses. Surg Endosc 2004;18:843–6. [11] Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:7–15.