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Transcervical thymectomy for thymoma in myasthenia gravis
Transcervical Thymectomy for Thymoma in Myasthenia Gravis
Gary Slater, MU, New York, New York Angelos E. Papatestas, MD, New York, New York Peter Kornfeld, MD, New York, New York Gabriel Genkins, MD, New York, New York
The treatment of choice for patients with myasthenia gravis with associated thymomas has been excision of the thymic tumor with thymectomy, usually through a sternal-splitting surgical approach [l-3]. Early surgical intervention has been generally accepted because of the potential invasive nature of these tumors [4,5]. Adoption of this policy has led to a considerable improvement in 5 year survival rates in most recent series [6-81. Early thymectomy in patients with generalized myasthenia gravis, with or without evidence of associated thymoma, has been advocated because of the increasing evidence of higher remission rates in patients with a short duration of symptoms before operation [9,10]. In patients without evident thymoma, thymectomy through a transcervical approach [II] has been the procedure of choice in our institution since 1967. A total of 451 transcervical thymectomies have been performed. Operative findings in this group revealed 29 instances of small unsuspected thymomas. In eight additional patients with small suspected thymomas, based on preoperative roentgenograms, the transcervical approach was also used.
Of the 37 patients with thymomas, 7 had an additional counter-incision made in the second intercostal space, as described by Klingen [12], to help mobilize the tumor, and 2 had a small portion of the manubrium removed for better exposure [13]. An analysis of the results of transcervical thymectomy in these 37 patients forms the basis of this report. In addition, we compared this group of patients with a group in whom thymectomy was performed through a transsternal approach, and who formed the basis of a previous report [14]. Material
and Methods
The records of all patients with myasthenia gravis who underwent thymectomy at the Mount Sinai Hospital through 1979 were reviewed. Patients with histologically confirmed thymomas were selected for study. Of this group From the Departments of Surgery and Medicine, Mount Sinai School of Medicine of the City University of New York, New York. Requests for reprints should be addressed to Gary Slater, MD, The Mount Sinai Medical Center, Department of Surgery, One Gustave L. Levy Place, New York, New York 10029.
254
of 133 patients, 37 had operation through a transcervical approach and 97 patients through a transsternal approach. One patient who had transcervical thymectomy subsequently underwent transsternal removal of a recurrent thymoma. The age and sex distribution of these patients is shown in Table I. The severity of myasthenic symptoms in patients operated on using the transcervical approach was classified using the Osserman classification (Table II) WI. The histologic classification of the thymomas removed through either the transcervical or transsternal approach was made by the predominant cell type. The majority of thymomas were classified as lymphoepithelial(81 percent in the transcervical group and 90 percent in the transsternal group), while the rest were mainly lymphocytic (except for 8 percent epithelial in the transcervical group). In the transcervical group, all thymomas except four were classified as noninvasive tumors. The determination that a tumor was noninvasive was made by the operating surgeon rather than the pathologist. Of the four invasive thymomas, three demonstrated early invasion of the pleura and one invaded the pericardium. In the transsternal group 45 tumors were noninvasive and 52 were invasive.
Results
There was no operative mortality in the 37 patients undergoing transcervical thymectomy, nor were there any major postoperative complications related to operation. The hospital stay of most patients was less than 7 days. The patients who stayed longer required prolonged hospitalization for adjustment of their medication to control myasthenic symptoms. There were eight deaths within 30 days of operation in the transsternal group. All patients in the transcervical group have had complete follow-up. The mean time of follow-up was 3.6 years. Eleven patients have been followed up for 5 or more years and 23 patients for more than 3 years. One patient was found to have a recurrent tumor. She underwent the first transcervical thymectomy performed at our hospital in 1967 for a thymoma that was suspected on chest roentgenography. Two years after thymectomy, she was reoperated on through a median sternotomy for a recurrent thymoma. Six years after the second operation she was free of tumor. In the last 5 years she has been lost to follow-up.
The American Journal of Surgery
Tr,anscervical
TABLE I
Males
Age
TS
30-39 40-49 50-59 60-69 7c-79 >'79
4 3 7 1 1
6 5 15 9 9 2
2 5 a 4
1 3 6 17 13 a
TDTAL
16
46
21
48
2
-
TC = transcervical;
Total TC TS
Females TS TC
TC
(vears)
TABLE II
Age and Sex of Patients with Thymomas at the Time of Thymectomy
2 6 a 15 5 1 37
TS = transsternal.
The treatment of a thymoma in a myasthenic patient is now well established: removal of the tumor with total thymectomy [2,3]. Resection of a thymoma (usually through a sternal-splitting approach) is now performed with an acceptably low mortality rate, though the postoperative morbidity rate remains high. Several large series [6,7] including our own [14] have documented mortality rates of less than 5 percent for thymectomy through a sternotomy in myasthenic patients. We have had the opportunity to evaluate the clinical course of a group of myasthenic patients who had a thymoma removed
Clinical Course of Myasthenic Patients With Thymomas Who Underwent Transcervical Thymectomy Remission
Improvement
Unchanged
Worse
Death
3 3
5 11
6 2
2 1
0 4
6
16
a
3
4
August 1982
Total
‘10 1 3 2
5 9 7
.
‘15 10 10 2
Total
16
21
37
100
:1. ‘,\
‘\
;
Volume 144,
Women
I IIA IIB Ill IV
2 80
- Total
Men
through a transcervical approach. The safety of this approach has been well documented in myasthenic patients without thymomas. In the 451 transcervical thymectomies performed in our institution, there has been one postoperative death related to thyroid storm and negligible morbidity. The question addressed in this report is whether removal of a thymoma through the transcervical approach increases the risk of tumor recurrence. Although our follow-up is not sufficiently long, from the accumulated data we have no evidence to support this hypothesis. We have not encountered a single recurrence in the patients with unsuspected thymomas. Since all thymic tumors removed (except four) have been noninvasive and, in fact, most have been incidental findings, one would expect a low recurrence rate and prolonged survival in t.hese patients. The group of patients who were operated on with a suspected preoperative diagnosis of thymoma was too small and had too short a follow-up compared with the larger group of patients who had an incidental thymoma found during thymectomy. The one recurrence in this group was in a patient operated on very early in our series (1967) and could represent an
Comments
Men Women
Gravis
97
There have been four delayed deaths, all of which were related to myasthenic respiratory insufficiency. In the transsternal group eight patients had either known recurrence or persistent tumor. Since not all patients in this group who died had autopsies, the number of recurrences may have been underestima ted. Table III summarizes the clinical course of the patients who had transcervical thymectomy. There were 5 complete remissions (asymptomatic patients off medication) and 13 patients with some improvement in myasthenic symptoms. A comparison of the cumulative 5 year survival rates in these patients with those in 97 myasthenic patients with thymomas operated on at our hospital [14] by the transsternal approach is shown in Figure 1.
TABLE III
in Myasthenia
Classification of Myasthenia Gravis in Patients With Thymomas at the Time of Transcervical Thymectomy
Class
1 9 11 32 22 17 2 3
Thymectomy
60
‘\
1
.-.
TRANSCERVICAL -.-.
‘.-__ --._ -*-__ TRANSSTERNAL --__ a*--___ ---..___
---__.
2
Ok----?
2
3
4
5
YEARS
Figure 1. Cumulative survival of patients with thymomas.
255
Slater et al
incomplete excision. The high incidence of recurrent tumors in the transsternal group is consistent with the relatively large number of invasive thymomas resected. Keynes [16] showed and we have confirmed [14] that myasthenic patients with thymomas tend to have a worse prognosis in terms of control of symptoms than patients without thymomas. In the present series we noted complete remission in 5 patients and improvement in 13. We feel that the early removal of thymomas is followed by a good clinical response and leads to easier management of myasthenic symptoms. Since adopting a policy of recommending transcervical thymectomy in all patients with myasthenia with generalized myasthenia gravis, regardless of age, we have noted a large increase in the number of unsuspected thymomas. This increase is particularly evident in older patients in whom thymoma is more common [17]. We feel that the evidence presented here justifies the continued use of a transcervical approach for the removal of small thymomas, even when they are suspected on preoperative chest roentgenograms. The use of a transcervical approach for the resection of thymomas will decrease the overall morbidity and mortality of surgery. We will continue following up these patients to see whether the long-term survival is satisfactory. The transsternal approach should be reserved for patients with large thymomas which for technical reasons are not accessible through the transcervical approach. Summary 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 un-
256
suspected 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. References 1. Braitman H, Li W, Herrmann C Jr, Mulder DG. Surgery for thymic tumors. Arch Surg 1971;103:14-6. 2. Thomas TV. Thymus and myasthenia gravis. Ann Thorac Surg 1972;16:141-6. 3. Weissberg D. Goldberg M, Pearson FG. Thymoma. Ann Thorac Surg 1972;13:499-512. 4. Castleman B. The pathology of the thymus gland in myasthenia gravis. Ann NY Acad Sci 1966;135:396-503. 5. Jain U, Frable WJ. Thymoma. J Thorac Cardiovasc Surg 1974;67:310-21. 6. Batata MA, Martini N, Huvos AG, Aguilar RI, Beattie EJ. Thymomas: clinicopathological features, therapy, and prognosis. Cancer 1974;34:369-96. 7. Bernatz PE, Harrison EG, Clagett OT. Thymoma: a clinicopathologic study. J Thorac Surg 1961;42:424-44. 6. Wilkins EW, Edmunds LH Jr, Castleman B. Cases of thymoma at the Massachusetts General Hospital. J Thorac Cardiovasc Surg 1966;52:322-8. 9. Buckingham JM, Howard F Jr, Bernatz PE, et al. The value of thymectomy in myasthenia gravis. A computer assisted matched study. Ann Surg 1976; 184:453-75. 10. Genkins G, Papatestas AE, Horowitz SH, Kornfeld P. Studies in myasthenia gravis: early thymectomy. Am J Med 1975; 48:517-24. 11. Papatestas AE, Genkins G, Kornfeld P. Horowitz SH, Kark AE. Transcervical thymectomy in myasthenia gravis. Surg Gynecol Obstet 1975;140:535-40. 12. Klingen G, Johansson L, Westerholm CJ, Sunstrom C. Transcervical thymectomy with the aid of mediastinoscopy for myasthenia gravis: eight years experience. Ann Thorac Surg 1977;23:342-7. 13. Kark AE. Papatestas AE. Some anatomical features of the transcervical approach for thymectomy. Mt Sinai J Med 1971;38:580-5. 14. Slater G, Papatestas AE, Genkins G, Kornfeld P, Horowitz SH, Bender A. Thymomas in patients with myasthenia gravis. Ann Surg 1978;188:171-4. 15. Osserman HE. Myasthenia gravis. New York: Grune and Stratton, 1958. 16. Keynes G. Surgery of the thymus gland. Second (and third) thoughts. Lancet 1954;1:1197-202. 17. Slater G, Papatestas AE, Genkins G, Kornfeld P, Horowitz SH. Thymectomy in patients more than forty years of age with, myasthenia gravis. Surg Gynecol Obstet 1978;146:54-6.
The American Journal of Surgery
Gary Slater, MU, New York, New York Angelos E. Papatestas, MD, New York, New York Peter Kornfeld, MD, New York, New York Gabriel Genkins, MD, New York, New York
The treatment of choice for patients with myasthenia gravis with associated thymomas has been excision of the thymic tumor with thymectomy, usually through a sternal-splitting surgical approach [l-3]. Early surgical intervention has been generally accepted because of the potential invasive nature of these tumors [4,5]. Adoption of this policy has led to a considerable improvement in 5 year survival rates in most recent series [6-81. Early thymectomy in patients with generalized myasthenia gravis, with or without evidence of associated thymoma, has been advocated because of the increasing evidence of higher remission rates in patients with a short duration of symptoms before operation [9,10]. In patients without evident thymoma, thymectomy through a transcervical approach [II] has been the procedure of choice in our institution since 1967. A total of 451 transcervical thymectomies have been performed. Operative findings in this group revealed 29 instances of small unsuspected thymomas. In eight additional patients with small suspected thymomas, based on preoperative roentgenograms, the transcervical approach was also used.
Of the 37 patients with thymomas, 7 had an additional counter-incision made in the second intercostal space, as described by Klingen [12], to help mobilize the tumor, and 2 had a small portion of the manubrium removed for better exposure [13]. An analysis of the results of transcervical thymectomy in these 37 patients forms the basis of this report. In addition, we compared this group of patients with a group in whom thymectomy was performed through a transsternal approach, and who formed the basis of a previous report [14]. Material
and Methods
The records of all patients with myasthenia gravis who underwent thymectomy at the Mount Sinai Hospital through 1979 were reviewed. Patients with histologically confirmed thymomas were selected for study. Of this group From the Departments of Surgery and Medicine, Mount Sinai School of Medicine of the City University of New York, New York. Requests for reprints should be addressed to Gary Slater, MD, The Mount Sinai Medical Center, Department of Surgery, One Gustave L. Levy Place, New York, New York 10029.
254
of 133 patients, 37 had operation through a transcervical approach and 97 patients through a transsternal approach. One patient who had transcervical thymectomy subsequently underwent transsternal removal of a recurrent thymoma. The age and sex distribution of these patients is shown in Table I. The severity of myasthenic symptoms in patients operated on using the transcervical approach was classified using the Osserman classification (Table II) WI. The histologic classification of the thymomas removed through either the transcervical or transsternal approach was made by the predominant cell type. The majority of thymomas were classified as lymphoepithelial(81 percent in the transcervical group and 90 percent in the transsternal group), while the rest were mainly lymphocytic (except for 8 percent epithelial in the transcervical group). In the transcervical group, all thymomas except four were classified as noninvasive tumors. The determination that a tumor was noninvasive was made by the operating surgeon rather than the pathologist. Of the four invasive thymomas, three demonstrated early invasion of the pleura and one invaded the pericardium. In the transsternal group 45 tumors were noninvasive and 52 were invasive.
Results
There was no operative mortality in the 37 patients undergoing transcervical thymectomy, nor were there any major postoperative complications related to operation. The hospital stay of most patients was less than 7 days. The patients who stayed longer required prolonged hospitalization for adjustment of their medication to control myasthenic symptoms. There were eight deaths within 30 days of operation in the transsternal group. All patients in the transcervical group have had complete follow-up. The mean time of follow-up was 3.6 years. Eleven patients have been followed up for 5 or more years and 23 patients for more than 3 years. One patient was found to have a recurrent tumor. She underwent the first transcervical thymectomy performed at our hospital in 1967 for a thymoma that was suspected on chest roentgenography. Two years after thymectomy, she was reoperated on through a median sternotomy for a recurrent thymoma. Six years after the second operation she was free of tumor. In the last 5 years she has been lost to follow-up.
The American Journal of Surgery
Tr,anscervical
TABLE I
Males
Age
TS
30-39 40-49 50-59 60-69 7c-79 >'79
4 3 7 1 1
6 5 15 9 9 2
2 5 a 4
1 3 6 17 13 a
TDTAL
16
46
21
48
2
-
TC = transcervical;
Total TC TS
Females TS TC
TC
(vears)
TABLE II
Age and Sex of Patients with Thymomas at the Time of Thymectomy
2 6 a 15 5 1 37
TS = transsternal.
The treatment of a thymoma in a myasthenic patient is now well established: removal of the tumor with total thymectomy [2,3]. Resection of a thymoma (usually through a sternal-splitting approach) is now performed with an acceptably low mortality rate, though the postoperative morbidity rate remains high. Several large series [6,7] including our own [14] have documented mortality rates of less than 5 percent for thymectomy through a sternotomy in myasthenic patients. We have had the opportunity to evaluate the clinical course of a group of myasthenic patients who had a thymoma removed
Clinical Course of Myasthenic Patients With Thymomas Who Underwent Transcervical Thymectomy Remission
Improvement
Unchanged
Worse
Death
3 3
5 11
6 2
2 1
0 4
6
16
a
3
4
August 1982
Total
‘10 1 3 2
5 9 7
.
‘15 10 10 2
Total
16
21
37
100
:1. ‘,\
‘\
;
Volume 144,
Women
I IIA IIB Ill IV
2 80
- Total
Men
through a transcervical approach. The safety of this approach has been well documented in myasthenic patients without thymomas. In the 451 transcervical thymectomies performed in our institution, there has been one postoperative death related to thyroid storm and negligible morbidity. The question addressed in this report is whether removal of a thymoma through the transcervical approach increases the risk of tumor recurrence. Although our follow-up is not sufficiently long, from the accumulated data we have no evidence to support this hypothesis. We have not encountered a single recurrence in the patients with unsuspected thymomas. Since all thymic tumors removed (except four) have been noninvasive and, in fact, most have been incidental findings, one would expect a low recurrence rate and prolonged survival in t.hese patients. The group of patients who were operated on with a suspected preoperative diagnosis of thymoma was too small and had too short a follow-up compared with the larger group of patients who had an incidental thymoma found during thymectomy. The one recurrence in this group was in a patient operated on very early in our series (1967) and could represent an
Comments
Men Women
Gravis
97
There have been four delayed deaths, all of which were related to myasthenic respiratory insufficiency. In the transsternal group eight patients had either known recurrence or persistent tumor. Since not all patients in this group who died had autopsies, the number of recurrences may have been underestima ted. Table III summarizes the clinical course of the patients who had transcervical thymectomy. There were 5 complete remissions (asymptomatic patients off medication) and 13 patients with some improvement in myasthenic symptoms. A comparison of the cumulative 5 year survival rates in these patients with those in 97 myasthenic patients with thymomas operated on at our hospital [14] by the transsternal approach is shown in Figure 1.
TABLE III
in Myasthenia
Classification of Myasthenia Gravis in Patients With Thymomas at the Time of Transcervical Thymectomy
Class
1 9 11 32 22 17 2 3
Thymectomy
60
‘\
1
.-.
TRANSCERVICAL -.-.
‘.-__ --._ -*-__ TRANSSTERNAL --__ a*--___ ---..___
---__.
2
Ok----?
2
3
4
5
YEARS
Figure 1. Cumulative survival of patients with thymomas.
255
Slater et al
incomplete excision. The high incidence of recurrent tumors in the transsternal group is consistent with the relatively large number of invasive thymomas resected. Keynes [16] showed and we have confirmed [14] that myasthenic patients with thymomas tend to have a worse prognosis in terms of control of symptoms than patients without thymomas. In the present series we noted complete remission in 5 patients and improvement in 13. We feel that the early removal of thymomas is followed by a good clinical response and leads to easier management of myasthenic symptoms. Since adopting a policy of recommending transcervical thymectomy in all patients with myasthenia with generalized myasthenia gravis, regardless of age, we have noted a large increase in the number of unsuspected thymomas. This increase is particularly evident in older patients in whom thymoma is more common [17]. We feel that the evidence presented here justifies the continued use of a transcervical approach for the removal of small thymomas, even when they are suspected on preoperative chest roentgenograms. The use of a transcervical approach for the resection of thymomas will decrease the overall morbidity and mortality of surgery. We will continue following up these patients to see whether the long-term survival is satisfactory. The transsternal approach should be reserved for patients with large thymomas which for technical reasons are not accessible through the transcervical approach. Summary 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 un-
256
suspected 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. References 1. Braitman H, Li W, Herrmann C Jr, Mulder DG. Surgery for thymic tumors. Arch Surg 1971;103:14-6. 2. Thomas TV. Thymus and myasthenia gravis. Ann Thorac Surg 1972;16:141-6. 3. Weissberg D. Goldberg M, Pearson FG. Thymoma. Ann Thorac Surg 1972;13:499-512. 4. Castleman B. The pathology of the thymus gland in myasthenia gravis. Ann NY Acad Sci 1966;135:396-503. 5. Jain U, Frable WJ. Thymoma. J Thorac Cardiovasc Surg 1974;67:310-21. 6. Batata MA, Martini N, Huvos AG, Aguilar RI, Beattie EJ. Thymomas: clinicopathological features, therapy, and prognosis. Cancer 1974;34:369-96. 7. Bernatz PE, Harrison EG, Clagett OT. Thymoma: a clinicopathologic study. J Thorac Surg 1961;42:424-44. 6. Wilkins EW, Edmunds LH Jr, Castleman B. Cases of thymoma at the Massachusetts General Hospital. J Thorac Cardiovasc Surg 1966;52:322-8. 9. Buckingham JM, Howard F Jr, Bernatz PE, et al. The value of thymectomy in myasthenia gravis. A computer assisted matched study. Ann Surg 1976; 184:453-75. 10. Genkins G, Papatestas AE, Horowitz SH, Kornfeld P. Studies in myasthenia gravis: early thymectomy. Am J Med 1975; 48:517-24. 11. Papatestas AE, Genkins G, Kornfeld P. Horowitz SH, Kark AE. Transcervical thymectomy in myasthenia gravis. Surg Gynecol Obstet 1975;140:535-40. 12. Klingen G, Johansson L, Westerholm CJ, Sunstrom C. Transcervical thymectomy with the aid of mediastinoscopy for myasthenia gravis: eight years experience. Ann Thorac Surg 1977;23:342-7. 13. Kark AE. Papatestas AE. Some anatomical features of the transcervical approach for thymectomy. Mt Sinai J Med 1971;38:580-5. 14. Slater G, Papatestas AE, Genkins G, Kornfeld P, Horowitz SH, Bender A. Thymomas in patients with myasthenia gravis. Ann Surg 1978;188:171-4. 15. Osserman HE. Myasthenia gravis. New York: Grune and Stratton, 1958. 16. Keynes G. Surgery of the thymus gland. Second (and third) thoughts. Lancet 1954;1:1197-202. 17. Slater G, Papatestas AE, Genkins G, Kornfeld P, Horowitz SH. Thymectomy in patients more than forty years of age with, myasthenia gravis. Surg Gynecol Obstet 1978;146:54-6.
The American Journal of Surgery