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The surgical treatment of invasive thymoma
The surgical treatment of invasive thymoma Resection with vascular reconstruction We have treated 96 patients with thymoma during the past 27 years; 57 of them had invasive thymoma. Surgical resection was undertaken in 45 of the 57 patients with invasive thymoma, including 14 patients in whom tumors were extirpated with vascular reconstruction. In addition, six patients with other thymic malignancies were treated in the same way. In six patients only angioplasty was performed, whereas artificial grafts were used in the other 14 patients. Ten of the 20 patients are still alive and weD. One has probably been cured, since no signs of recurrence have been noted during the postoperative foDow-up period of 8 years. No complications or occlusive symptoms were observed in these patients postoperatively, except in one who died after gastrointestinal hemorrhage. In one patient long-term patency of the vascular graft was confirmed by angiography and magnetic resonance imaging 5 years after operation. This intensive surgical procedure improved the quality of life for patients with the superior vena caval syndrome and may also have improved the prognosis of the patients with invasive thymoma. (J 'fHORAC CARDIOVASC SURG 1992;103:414-20)
Nobuyoshi Shimizu, MD, Shigeharu Moriyama, MD, Motoi Aoe, MD, Masao Nakata, MD, Akio Ando, MD, and Shigeru Teramoto, MD, Okayama, Japan
h e prognosis of patients receiving surgical treatment for thymoma is favorable when the thymoma is of the encapsulated type. However, the operative results are less satisfactory when the adjacent organs are invaded by thymoma that has broken through its capsule. We have treated 96 patients with thymoma during the past 27 years; 57 had invasive thymoma and 39 had an encapsulated tumor. In 14 of these patients the invasive thymoma was extirpated and vascular reconstruction was performed. We report the results of the surgical treatment of invasive thymoma, and, in particular, those of the concomitant resection of the great veins with vascular reconstruction by angioplasty or grafting.
Table I. Thymoma
Patients
Figures in parentheses indicate tumors not resected.
The study comprised 96 patients with thymoma who were treated at our department during the 27-year period from 1963 to 1989. Thirty-nine patients had an encapsulated thymoma and From the Second Department of Surgery, Okayama University Medical School, Okayama, Japan. Received for publication Feb. 15, 1989. Accepted for publication Jan. 25, 1991. Address for reprints: Nobuyoshi Shimizu, MD, Second Department of Surgery, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700, Japan.
12/1/28298
414
Encapsulated
Invasive
Epithelial cell type Mixed cell type Lymphocytic type
21 II
19 (6) 24 (4) 14 (2)
Total
39
57 (I 2)
Associated disease Myasthenia gravis Pure red cell aplasia Colon cancer Hyperthyroidism Sjogren's syndrome with hypergammaglobulinemia
7
23 4
3 1
1
57 patients, invasive. The growths were histologically classified in terms of the degree of lymphocytic infiltration. The epithelial cell type was invasive, but there was no difference in the ratio of encapsulated to invasive tumors between the mixed and lymphocytic types. Tumors were resected in 84 patients, a resectability rate of 87.5%. We were unable to extirpate the lesion in 12 patients, and exploratory thoracotomies were performed in nine of them. Histologic diagnosis was made by biopsy of the cervical lymph node or the chest wall in the remaining three patients. The thymomas were associated with myasthenia gravis in 23
Volume 103
Surgical treatment of invasive thymoma
Number 3 March 1992
4I5
91.0 % N
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= 39
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2
3
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7
6
8
9
year
10
Postoperative Survival Time Fig. 1. Survival of patients with thymoma of the encapsulated and invasive types. There is a statistically significant difference between the two groups.
% 100
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57.9 % N = 42
-,
N=25
mixed .tvpe lymphocytic type
L_-,
L 31.1 % N = 25
epithelial cell type
20 10 0
0
2
3
4
5
6
7
8
9
10
year
Postoperative Survival Time Fig. 2. Survival of patients with thymoma for each histologic type, including both resected and nonresected tumors. A statistically significant difference was seen between the mixed and epithelial types.
Results patients, pure red cell aplasia in four, colon cancer in three, and hyperthyroidism in one. In one patient the tumor was associated with both hypergammaglobulinemia and Sjogren's syndrome (Table I).
The 5-year and IO-year survival rates were 94.2% and 91.0%, respectively, for the 39 patients with encapsulated thymoma. In the 57 patients with invasive thymoma
41 6
The Journal of Thoracic and Cardiovascular
Shimizu et al.
Surgery
% 100 90
,:
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30
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= 19 cell type
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o
2
3
4
5
6
7
8
9
10
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year
Postoperative Survival Time
Fig. 3. Survivalof patients with resected thymoma of each histologic type. There were no statistically significant differences among the three groups.
Fig. 4. Reconstruction of left brachiocephalic vein. This type of operation was performedfor seven patients (cases 7 to 13).
the corresponding survival rates were 46.9% and 15.4%. The difference in survival between the groups was statistically significant (generalized Wilcoxon paired comparison test, p < 0.01) (Fig. 1). When survival rates for all patients, including those with an unresectable lesion, were analyzed according to the histologic classification, the 5and lO-year survival rates were 80.1% and 57.9% for mixed cell type thymoma (42 patients), followed by 63.6% and 51.8% for lymphocytic thymoma (25 patients). The rates for patients with epithelial cell thymoma (25 patients) were 43.6% and 31.3%, respectively. A significant difference (p < 0.05) in survival rate
was observed between the mixed cell and epithelial cell types (Fig. 2). Overall, the prognosis for patients with invasive thymoma was worse than that for those with an encapsulated tumor, and the prognosis for those with epithelial cell thymomas was worse than that for those with mixed cell type tumors. However, when complete resection or debulking of the tumor was undertaken, no significant differences were observed between the histologic types. The 5-year and 1O-year survival rates then became 82.0% and 60.9% for the mixed type and 64.1% and 51.4%, respectively, for the lymphocytic type. Even in the epithelial cell type, the 5-year and 1a-year survival ra tes were 63.8% and 45.6%, respectively. No statistically significant differences were observed between the histologic groups (Fig. 3). Since invasive thymoma often infiltrates the left brachiocephalic vein and superior vena cava (SVC) via the thymic vein, we performed vascular reconstruction in addition to tumor resection in some of these patients. Vascular reconstruction was undertaken in 14 patients with thymoma and in six patients with other thymic malignancies up to the end of 1989. Hodgkin's lymphoma, non-Hodgkin's malignant lymphoma, carcinoma, carcinoid tumor, and seminoma of thymic origin constituted the other malignancies. The SVC syndrome appeared in seven of these 20 patients before the operation. Angioplasty alone was performed in six patients, and artificial grafts were used in the other 14. The left
Volume 103
Number 3 March 1992
Surgical treatment ofinvasive thymoma
4I7
Table II. Angioplasty for invasive thymoma and thymic malignancies Patient No.
Age/sex
I 2 3 4 5
50/M 28/M 52/M 48/M 56/F
6
35/M
Diagnosis Invasive thymoma with Invasive thymoma with Invasive thymoma with Invasive thymoma with Invasive thymoma with syndrome Malignant lymphoma
SVC syndrome SVC syndrome SVC syndrome MG Sjogren's
Resected vessels
Angioplasty
Patient outcome
SVC and LBCV SVC and LBCV LBCV SVCand LBCV LBCV
RA and LBCV; ECB SVC and LBCV LBCV SVC and LBCV LBCV
DOD 3 yr postop. DOD 3 mo postop. DOD 8 mo postop. NED for 7 yr NED for 4 yr
LBCV
LBCV
NED for 2 yr
SYC, Superior vena cava; LBCY, left brachiocephalicvein, RA; right atrium; ECB, extracorporeal bypass;DOD; died of disease; NED, no evidenceof disease; MG, myasthenia gravis.
Table III. Reconstruction of LBCV in invasive thymoma and thymic malignancies Patient No.
Age/sex
Diagnosis
Resected vessel
7 8
71/F 42/M
LBCV LBCV
LBCV LBCV
9
10
65/M 57/M
Invasive thymoma Invasive thymoma with SVC syndrome Invasive thymoma Invasive thymoma
LBCV LBCV
LBCV LBCV
II
41/M
Thymic seminoma
LBCV
LBCV
12
211M
LBCV
13
62/M
Thymic Hodgkin's lymphoma Thymic carcinoid
LBCV
Reconstruction
Applied graft
Graft patency Patent by angiography No sign of occlusion
LBCV
ePTFE ePTFE with ring ePTFE ePTFE with ring ePTFE with ring ePTFE
LBCV
ePTFE
Patient outcome
No sign of occlusion Patent by angiography
DOD 2 yr Died of respiratory failure NED for 4 yr NED for 3 yr
Patent by angiography
NED for 2 yr
Patent by angiography
DOD I yr
Patent by angiography
NED for 2 yr
SYC, Superior vena cava; LBCY, left brachiocephalicvein; ePTFE, expanded polytetrafluoroethylene graft; DOD, died of disease; NED, no evidenceof disease.
Table IV. Reconstruction of SVC and LBCV in invasive thymoma and thymic malignancies Patient No.
Age/sex
Diagnosis
14
44/M
15
69/M
16
66/M
Invasive thymoma with SVC syndrome Thymic Hodgkin's lymphoma Invasive thymoma
I7
48/M
18
34/M
19
55/M
Thymic carcinoma with SVC syndrome Invasive thymoma with SVC syndrome Invasive thymoma
20
75/M
Invasive thymoma
Resected vessels
Reconstruction
SVCand LBCV SVCand LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVCand LBCV SVC and LBCV
SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV
Applied graft
Graft patency
Teflon graft
Patent by angiography
DOD I yr
Teflon graft
Occluded before death
ePTFE with ring ePTFE
Patent by angiography
Died of GI bleeding 45th postop day DOD 2 mo
Patent by autopsy
DOD 2 mo
ePTFE
Patent by angiography
NED for 8 yr
ePTFE with ring ePTFE with ring
Patent by angiography
NED for 5 yr
Patent by angiography
NED for I yr
Postop outcome
SYC, Superior vena cava; LBCY; left brachicephalic vein; DOD, died of disease; GI, gastrointestinal; ePTFE; expanded polytetrafluoroethylene graft; NED, no evidence of disease.
brachiocephalic vein was reconstructed with an artificial graft in seven patients and both the SVC and the left brachiocephalic vein in another seven patients (Tables II, III, and IV). The postoperative course and follow-up angiograms evinced a favorable outcome, except in one patient
(case 15). In this patient angiography revealed no evidence of occlusion on postoperative day 25. However, the patient died of SVC syndrome on day 45, when hemostatics were used in the management of gastrointestinal bleeding that had occurred during the course of respira-
4 I8
The Journal of Thoracic and Cardiovascular Surgery
Shimizu et at.
No. 14. 44 Y - 0 female Invasive thymoma with SVC syndrome
No. 15. 69 Y - 0 male Thymic Hodgkin's lymphoma
No. 16. 66 Y - 0 male Invasive thymoma with SVC syndrome
No. 18. 34 Y - 0 male Invasive thymoma with SVC syndrome
No. 19. 55 Y - 0 male Invasive thymoma with SVC syndrome
No. 20. 75 Y - 0 male Invasive thymoma with SVC syndrome
No. 17. 48 Y - 0 male Thymic carcinoma with SVC syndrome
Fig. 5. Reconstruction of SYC.
tory insufficiency. No occlusive symptoms were seen in any of the other patients from 35 days to 5 years after operation, during which period the patency of the grafts was confirmed by angiography, magnetic resonance imaging, and clinical findings. Angioplasty without grafting was performed in six patients. In two of these six, infiltrations were recognized in both the left brachiocephalic vein and the SVC, and tumor emboli were observed in patients 1 and 3. Since in patient I the tumor extended as far as the right atrium, the affected lesion was resected with the aid of cardiopulmonary bypass. No severe perioperativecomplications were encountered in these patients. The operative methods used for vascular reconstruction of the left brachiocephalic vein are shown in Fig. 4. In all these patients the left brachiocephalic vein was reconstructed with an expanded polytetrafluoroethylene
(ePTFE) graft having a diameter of 10 to 12 mm with or without rings. No signs of obstruction of the grafts were observed in any of the six patients. Four are doing well (2 to 4 years postoperatively); the other three have died of recurrence or respiratory failure. The operative methods used for vascular reconstruction of the brachiocephalic vein and SVC are shown in Fig. 5. Teflon artificial grafts were used in patients 14and 15 and ePTFE artificial grafts were used for patients 17 and 18. ePTFE grafts with rings were used in patients 16, 19, and 20. In all these patients, the reconstruction was first performed between the left brachiocephalic vein and the right atrium. The SVC was reconstructed in five patients, and a patch graft was applied in one. The veins were extensively resected in one patient (No. 15), and the SVC was not reconstructed. No severe complications were encountered, except for gastrointestinal bleeding
Volume 103 Number 3 March 1992
Surgical treatment of invasive thymoma
4 19
Fig. 6. Venogram 4 years afteroperation showed satisfactory patency of the graft replacing the SVC and the left brachiocephalic vein. and occlusion of the grafted vessels in the aforementioned patient. Although patients 14, 15, 16,and 17died during the early postoperative period,patients 18, 19,and 20 are still alive with no signs of recurrence. Patient 18, in particular, has remained trouble free for 8 years after operation, and long-term survival can thus be expected. As for the patency of the replaced artificial grafts, occlusion was observedin only one patient. In patient 19, patency at 4 and 5 years was confirmed by angiography (Fig. 6) and magnetic resonanceimaging (Fig. 7), respectively. Postoperative radiotherapy was routinelyadministered to patients with invasive thymoma, except in patients in whom perioperative difficulties were encountered. Prognosis
Favorableoperative results were not always obtained, but at the time of writing 10 patients are alive and doing well. These 10 patients have survived for periods ranging from 1to 8 years.Patients 4 and 5, both of whom received angioplasty, have survived for 4 and 7 years. Patients 9, 10, 11,and 13 have survived for 2 to 4 years after reconstruction of the left brachiocephalic vein. The patients undergoing reconstruction of both the SVC and the left brachiocephalic vein had advanced disease, and a good prognosis was not expected. Patient 18 had an epithelial cellthymoma infiltrating the SVC and the brachioceph-
Fig. 7. Magnetic resonance imaging 5 years after operation revealed patency of SVC graft (arrow). alic vein.The affected regionswere resected and successfully reconstructed with ePTFE artificial grafts. This patient has had no sign of recurrence during the subsequent 8-year period. Patients i 9 and 20 have survived 5 and 2 years, respectively. Discussion
Postoperative results in patients with invasivethymoma are not favorable in general. The 5-year survival rate in our patients was 46.9%. Bernatz and associates' reported a similar rate of 43%. Five-and 1O-year survival rates of 55%and 40%,respectively, have been reported by Wilkinsand Cathleman.i and a rate of 49.4%for 10-year survivalhas been reported by Fujimura and coworkers.' Similar results have been described by various other authors." Although invasive lesions infiltrating the blood vessels are difficultto resect, we have, so far, resected 20 such lesions and have performed successfulconcomitant vascular reconstruction. Doty'' reported 10 cases of SVC obstruction resulting from benign and malignant mediastinal disease. Relief of the SVC syndrome and prolongation of survivalwere obtained by operation. However, no patients with thymoma were included in his series. Recently Doty, Doty, and Jones" reported nine cases of
The Journal of Thoracic and Cardiovascular
420 Shimizu et al.
SVC reconstruction with composite spiral vein grafts. In seven the grafts have remained patent for periods of up,to nearly 15 years. Tsubota and coworkers? reconstructed the vena cava in five of 15 patients with invasive thymoma and reported that the vascular grafts were patent in four patients 1 month after the operation, two patients surviving for 4 years. They considered that such an extensive operation may improve the prognosis. Recently SVC replacement with PTFE grafts has been performed by Dartevelle and colleagues'' in 13 patients with mediastinal-pulmonary malignant tumors. Five of these patients are still living, with the longest postoperative follow-up period being 60 months and the overall cumulative survival rate 27% at 3 years. Our group? also previously reported results of the surgical treatment of thymoma, including vascular reconstruction. This therapeutic method appears to be promising, since survival times of longer than 5 years have been achieved. Kitagawa and coworkers.!" referring to their patients with unresectable thymoma, mentioned that lesions infiltrating the SVC were responsible for poor prognosis. However, the prognosis may have been altered when these lesions were resected. ePTFE grafts have been reported to remain patent for 4 years by Garcia-Rinaldi and associates. I I Patency of an ePTFE graft was also demonstrated in one of our patients at 5 years. Such long-term patency relieves the symptoms of SVC syndrome and also may improve the prognosis for patients with invasive thymomas.
Conclusion Vascular reconstructions were performed in 20 patients: Fourteen had invasive thymoma, two had thymic Hodgkin's lymphoma, one had thymic non-Hodgkin's lymphoma, one had thymic carcinoma, one had thymic carcinoid tumor, and one had thymic seminoma. Six patients underwent only angioplasty, whereas artificial grafts were used in 14 patients. In only one of these patients were complications of the vascular operation or occlusive symptoms recognized postoperatively. Eight of
Surgery
the 16 patients are still alive. One is considered possibly cured since no signs of recurrence have been detected during a postoperative follow-up period of 8 years. REFERENCES 1. Bernatz PE, Khousari S, Harrison EG, Taylor WF. Thymoma: factors influencing prognosis. Surg Clin North Am 1973;53:885-91.
2. WilkinsEW, Cathleman B.Thymoma:a continuingsurvey at the Massachusetts General Hospital. Ann Thorac Surg 1979;28:252-6.
3. Fujimura S, Kondo T, Handa M, et al. Results of surgical treatment for thymoma based on 66 patients. J THoRAc CARDIOVASC SURG 1987;93:708-14. 4. LewislE, Wick MR, Scheithauer BW, Bernatz PE, et al. Thymoma: clinicopathological review. Cancer 1978;60: 2727-43.
5. Doty DB. Bypassof superior vena cava: six years' experience with spiral veingraft for obstruction of superiorvena cava due to benignand malignant disease. J THoRAc CARDIOVASC SURG 1982;83:326-38. 6. Doty DB, Doty JR, Jones KW. Bypass of superior vena cava: fifteen years' experience with spiral vein graft for obstructionof superiorvenacava caused by benigndisease. J THoRAc CARDIOVASC SURG 1990;99:889-96. 7. Tsubota N, Yamashita C, Ishii N, et al. The resultsof surgical treatment of invasive thymoma and thymus related tumors. Jpn J Thorac Surg 1985;86:752-61. 8. DartevelleP, Chapelier A, Navajas M, et al. Replacement of the superior vena cava with polytetrafluoroethylene grafts combined with resection of mediastinal-pulmonary malignant tumors. J THORAC CARDIOVASC SURG 1987; 94:361-6.
9. Shimizu N, Kurita A, Kunikata E, Hara F, YamamotoS, Teramoto S. The resultsof surgicaltreatment of thymoma. Rinsho Kyobu Geka 1983;3:424-9. 10. Kitagawa Y, Monden Y, Nakahara K, et al. The resultsof surgical treatment of 117 patients with thymoma. Jpn J Thorac Surg 1984;32:72-7. 11. Garcia-Rinaldi R, Zamora JL, Torres-Salichs M, et al. Four-year patencyof PTFE grafts after replacementof the superiorvenacavaand the innominateveins.Tex Heart Inst J 1988;15:192-4.
Nobuyoshi Shimizu, MD, Shigeharu Moriyama, MD, Motoi Aoe, MD, Masao Nakata, MD, Akio Ando, MD, and Shigeru Teramoto, MD, Okayama, Japan
h e prognosis of patients receiving surgical treatment for thymoma is favorable when the thymoma is of the encapsulated type. However, the operative results are less satisfactory when the adjacent organs are invaded by thymoma that has broken through its capsule. We have treated 96 patients with thymoma during the past 27 years; 57 had invasive thymoma and 39 had an encapsulated tumor. In 14 of these patients the invasive thymoma was extirpated and vascular reconstruction was performed. We report the results of the surgical treatment of invasive thymoma, and, in particular, those of the concomitant resection of the great veins with vascular reconstruction by angioplasty or grafting.
Table I. Thymoma
Patients
Figures in parentheses indicate tumors not resected.
The study comprised 96 patients with thymoma who were treated at our department during the 27-year period from 1963 to 1989. Thirty-nine patients had an encapsulated thymoma and From the Second Department of Surgery, Okayama University Medical School, Okayama, Japan. Received for publication Feb. 15, 1989. Accepted for publication Jan. 25, 1991. Address for reprints: Nobuyoshi Shimizu, MD, Second Department of Surgery, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700, Japan.
12/1/28298
414
Encapsulated
Invasive
Epithelial cell type Mixed cell type Lymphocytic type
21 II
19 (6) 24 (4) 14 (2)
Total
39
57 (I 2)
Associated disease Myasthenia gravis Pure red cell aplasia Colon cancer Hyperthyroidism Sjogren's syndrome with hypergammaglobulinemia
7
23 4
3 1
1
57 patients, invasive. The growths were histologically classified in terms of the degree of lymphocytic infiltration. The epithelial cell type was invasive, but there was no difference in the ratio of encapsulated to invasive tumors between the mixed and lymphocytic types. Tumors were resected in 84 patients, a resectability rate of 87.5%. We were unable to extirpate the lesion in 12 patients, and exploratory thoracotomies were performed in nine of them. Histologic diagnosis was made by biopsy of the cervical lymph node or the chest wall in the remaining three patients. The thymomas were associated with myasthenia gravis in 23
Volume 103
Surgical treatment of invasive thymoma
Number 3 March 1992
4I5
91.0 % N
:,
= 39
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2
3
5
4
7
6
8
9
year
10
Postoperative Survival Time Fig. 1. Survival of patients with thymoma of the encapsulated and invasive types. There is a statistically significant difference between the two groups.
% 100
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, '-----------------1 __ ~0.1 %
90
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80 ell
70
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Q)
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51.8%
L-
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L
57.9 % N = 42
-,
N=25
mixed .tvpe lymphocytic type
L_-,
L 31.1 % N = 25
epithelial cell type
20 10 0
0
2
3
4
5
6
7
8
9
10
year
Postoperative Survival Time Fig. 2. Survival of patients with thymoma for each histologic type, including both resected and nonresected tumors. A statistically significant difference was seen between the mixed and epithelial types.
Results patients, pure red cell aplasia in four, colon cancer in three, and hyperthyroidism in one. In one patient the tumor was associated with both hypergammaglobulinemia and Sjogren's syndrome (Table I).
The 5-year and IO-year survival rates were 94.2% and 91.0%, respectively, for the 39 patients with encapsulated thymoma. In the 57 patients with invasive thymoma
41 6
The Journal of Thoracic and Cardiovascular
Shimizu et al.
Surgery
% 100 90
,:
~-_.:~-----, ........ ~--,
80
L....;-··1
LL_,
"1
70
L-L
~~%
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.... - - -- - -- --- -. - -- -- - --:":l---- - -- --- -------,
60
:
L
50
:
N
= 23
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40
N
30
mixed type lymphocytic type epithelial
= 19 cell type
20 10 OL...--I---JL....--I----J_....l----J_....l----'_....l----'
o
2
3
4
5
6
7
8
9
10
_
year
Postoperative Survival Time
Fig. 3. Survivalof patients with resected thymoma of each histologic type. There were no statistically significant differences among the three groups.
Fig. 4. Reconstruction of left brachiocephalic vein. This type of operation was performedfor seven patients (cases 7 to 13).
the corresponding survival rates were 46.9% and 15.4%. The difference in survival between the groups was statistically significant (generalized Wilcoxon paired comparison test, p < 0.01) (Fig. 1). When survival rates for all patients, including those with an unresectable lesion, were analyzed according to the histologic classification, the 5and lO-year survival rates were 80.1% and 57.9% for mixed cell type thymoma (42 patients), followed by 63.6% and 51.8% for lymphocytic thymoma (25 patients). The rates for patients with epithelial cell thymoma (25 patients) were 43.6% and 31.3%, respectively. A significant difference (p < 0.05) in survival rate
was observed between the mixed cell and epithelial cell types (Fig. 2). Overall, the prognosis for patients with invasive thymoma was worse than that for those with an encapsulated tumor, and the prognosis for those with epithelial cell thymomas was worse than that for those with mixed cell type tumors. However, when complete resection or debulking of the tumor was undertaken, no significant differences were observed between the histologic types. The 5-year and 1O-year survival rates then became 82.0% and 60.9% for the mixed type and 64.1% and 51.4%, respectively, for the lymphocytic type. Even in the epithelial cell type, the 5-year and 1a-year survival ra tes were 63.8% and 45.6%, respectively. No statistically significant differences were observed between the histologic groups (Fig. 3). Since invasive thymoma often infiltrates the left brachiocephalic vein and superior vena cava (SVC) via the thymic vein, we performed vascular reconstruction in addition to tumor resection in some of these patients. Vascular reconstruction was undertaken in 14 patients with thymoma and in six patients with other thymic malignancies up to the end of 1989. Hodgkin's lymphoma, non-Hodgkin's malignant lymphoma, carcinoma, carcinoid tumor, and seminoma of thymic origin constituted the other malignancies. The SVC syndrome appeared in seven of these 20 patients before the operation. Angioplasty alone was performed in six patients, and artificial grafts were used in the other 14. The left
Volume 103
Number 3 March 1992
Surgical treatment ofinvasive thymoma
4I7
Table II. Angioplasty for invasive thymoma and thymic malignancies Patient No.
Age/sex
I 2 3 4 5
50/M 28/M 52/M 48/M 56/F
6
35/M
Diagnosis Invasive thymoma with Invasive thymoma with Invasive thymoma with Invasive thymoma with Invasive thymoma with syndrome Malignant lymphoma
SVC syndrome SVC syndrome SVC syndrome MG Sjogren's
Resected vessels
Angioplasty
Patient outcome
SVC and LBCV SVC and LBCV LBCV SVCand LBCV LBCV
RA and LBCV; ECB SVC and LBCV LBCV SVC and LBCV LBCV
DOD 3 yr postop. DOD 3 mo postop. DOD 8 mo postop. NED for 7 yr NED for 4 yr
LBCV
LBCV
NED for 2 yr
SYC, Superior vena cava; LBCY, left brachiocephalicvein, RA; right atrium; ECB, extracorporeal bypass;DOD; died of disease; NED, no evidenceof disease; MG, myasthenia gravis.
Table III. Reconstruction of LBCV in invasive thymoma and thymic malignancies Patient No.
Age/sex
Diagnosis
Resected vessel
7 8
71/F 42/M
LBCV LBCV
LBCV LBCV
9
10
65/M 57/M
Invasive thymoma Invasive thymoma with SVC syndrome Invasive thymoma Invasive thymoma
LBCV LBCV
LBCV LBCV
II
41/M
Thymic seminoma
LBCV
LBCV
12
211M
LBCV
13
62/M
Thymic Hodgkin's lymphoma Thymic carcinoid
LBCV
Reconstruction
Applied graft
Graft patency Patent by angiography No sign of occlusion
LBCV
ePTFE ePTFE with ring ePTFE ePTFE with ring ePTFE with ring ePTFE
LBCV
ePTFE
Patient outcome
No sign of occlusion Patent by angiography
DOD 2 yr Died of respiratory failure NED for 4 yr NED for 3 yr
Patent by angiography
NED for 2 yr
Patent by angiography
DOD I yr
Patent by angiography
NED for 2 yr
SYC, Superior vena cava; LBCY, left brachiocephalicvein; ePTFE, expanded polytetrafluoroethylene graft; DOD, died of disease; NED, no evidenceof disease.
Table IV. Reconstruction of SVC and LBCV in invasive thymoma and thymic malignancies Patient No.
Age/sex
Diagnosis
14
44/M
15
69/M
16
66/M
Invasive thymoma with SVC syndrome Thymic Hodgkin's lymphoma Invasive thymoma
I7
48/M
18
34/M
19
55/M
Thymic carcinoma with SVC syndrome Invasive thymoma with SVC syndrome Invasive thymoma
20
75/M
Invasive thymoma
Resected vessels
Reconstruction
SVCand LBCV SVCand LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVCand LBCV SVC and LBCV
SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV SVC and LBCV
Applied graft
Graft patency
Teflon graft
Patent by angiography
DOD I yr
Teflon graft
Occluded before death
ePTFE with ring ePTFE
Patent by angiography
Died of GI bleeding 45th postop day DOD 2 mo
Patent by autopsy
DOD 2 mo
ePTFE
Patent by angiography
NED for 8 yr
ePTFE with ring ePTFE with ring
Patent by angiography
NED for 5 yr
Patent by angiography
NED for I yr
Postop outcome
SYC, Superior vena cava; LBCY; left brachicephalic vein; DOD, died of disease; GI, gastrointestinal; ePTFE; expanded polytetrafluoroethylene graft; NED, no evidence of disease.
brachiocephalic vein was reconstructed with an artificial graft in seven patients and both the SVC and the left brachiocephalic vein in another seven patients (Tables II, III, and IV). The postoperative course and follow-up angiograms evinced a favorable outcome, except in one patient
(case 15). In this patient angiography revealed no evidence of occlusion on postoperative day 25. However, the patient died of SVC syndrome on day 45, when hemostatics were used in the management of gastrointestinal bleeding that had occurred during the course of respira-
4 I8
The Journal of Thoracic and Cardiovascular Surgery
Shimizu et at.
No. 14. 44 Y - 0 female Invasive thymoma with SVC syndrome
No. 15. 69 Y - 0 male Thymic Hodgkin's lymphoma
No. 16. 66 Y - 0 male Invasive thymoma with SVC syndrome
No. 18. 34 Y - 0 male Invasive thymoma with SVC syndrome
No. 19. 55 Y - 0 male Invasive thymoma with SVC syndrome
No. 20. 75 Y - 0 male Invasive thymoma with SVC syndrome
No. 17. 48 Y - 0 male Thymic carcinoma with SVC syndrome
Fig. 5. Reconstruction of SYC.
tory insufficiency. No occlusive symptoms were seen in any of the other patients from 35 days to 5 years after operation, during which period the patency of the grafts was confirmed by angiography, magnetic resonance imaging, and clinical findings. Angioplasty without grafting was performed in six patients. In two of these six, infiltrations were recognized in both the left brachiocephalic vein and the SVC, and tumor emboli were observed in patients 1 and 3. Since in patient I the tumor extended as far as the right atrium, the affected lesion was resected with the aid of cardiopulmonary bypass. No severe perioperativecomplications were encountered in these patients. The operative methods used for vascular reconstruction of the left brachiocephalic vein are shown in Fig. 4. In all these patients the left brachiocephalic vein was reconstructed with an expanded polytetrafluoroethylene
(ePTFE) graft having a diameter of 10 to 12 mm with or without rings. No signs of obstruction of the grafts were observed in any of the six patients. Four are doing well (2 to 4 years postoperatively); the other three have died of recurrence or respiratory failure. The operative methods used for vascular reconstruction of the brachiocephalic vein and SVC are shown in Fig. 5. Teflon artificial grafts were used in patients 14and 15 and ePTFE artificial grafts were used for patients 17 and 18. ePTFE grafts with rings were used in patients 16, 19, and 20. In all these patients, the reconstruction was first performed between the left brachiocephalic vein and the right atrium. The SVC was reconstructed in five patients, and a patch graft was applied in one. The veins were extensively resected in one patient (No. 15), and the SVC was not reconstructed. No severe complications were encountered, except for gastrointestinal bleeding
Volume 103 Number 3 March 1992
Surgical treatment of invasive thymoma
4 19
Fig. 6. Venogram 4 years afteroperation showed satisfactory patency of the graft replacing the SVC and the left brachiocephalic vein. and occlusion of the grafted vessels in the aforementioned patient. Although patients 14, 15, 16,and 17died during the early postoperative period,patients 18, 19,and 20 are still alive with no signs of recurrence. Patient 18, in particular, has remained trouble free for 8 years after operation, and long-term survival can thus be expected. As for the patency of the replaced artificial grafts, occlusion was observedin only one patient. In patient 19, patency at 4 and 5 years was confirmed by angiography (Fig. 6) and magnetic resonanceimaging (Fig. 7), respectively. Postoperative radiotherapy was routinelyadministered to patients with invasive thymoma, except in patients in whom perioperative difficulties were encountered. Prognosis
Favorableoperative results were not always obtained, but at the time of writing 10 patients are alive and doing well. These 10 patients have survived for periods ranging from 1to 8 years.Patients 4 and 5, both of whom received angioplasty, have survived for 4 and 7 years. Patients 9, 10, 11,and 13 have survived for 2 to 4 years after reconstruction of the left brachiocephalic vein. The patients undergoing reconstruction of both the SVC and the left brachiocephalic vein had advanced disease, and a good prognosis was not expected. Patient 18 had an epithelial cellthymoma infiltrating the SVC and the brachioceph-
Fig. 7. Magnetic resonance imaging 5 years after operation revealed patency of SVC graft (arrow). alic vein.The affected regionswere resected and successfully reconstructed with ePTFE artificial grafts. This patient has had no sign of recurrence during the subsequent 8-year period. Patients i 9 and 20 have survived 5 and 2 years, respectively. Discussion
Postoperative results in patients with invasivethymoma are not favorable in general. The 5-year survival rate in our patients was 46.9%. Bernatz and associates' reported a similar rate of 43%. Five-and 1O-year survival rates of 55%and 40%,respectively, have been reported by Wilkinsand Cathleman.i and a rate of 49.4%for 10-year survivalhas been reported by Fujimura and coworkers.' Similar results have been described by various other authors." Although invasive lesions infiltrating the blood vessels are difficultto resect, we have, so far, resected 20 such lesions and have performed successfulconcomitant vascular reconstruction. Doty'' reported 10 cases of SVC obstruction resulting from benign and malignant mediastinal disease. Relief of the SVC syndrome and prolongation of survivalwere obtained by operation. However, no patients with thymoma were included in his series. Recently Doty, Doty, and Jones" reported nine cases of
The Journal of Thoracic and Cardiovascular
420 Shimizu et al.
SVC reconstruction with composite spiral vein grafts. In seven the grafts have remained patent for periods of up,to nearly 15 years. Tsubota and coworkers? reconstructed the vena cava in five of 15 patients with invasive thymoma and reported that the vascular grafts were patent in four patients 1 month after the operation, two patients surviving for 4 years. They considered that such an extensive operation may improve the prognosis. Recently SVC replacement with PTFE grafts has been performed by Dartevelle and colleagues'' in 13 patients with mediastinal-pulmonary malignant tumors. Five of these patients are still living, with the longest postoperative follow-up period being 60 months and the overall cumulative survival rate 27% at 3 years. Our group? also previously reported results of the surgical treatment of thymoma, including vascular reconstruction. This therapeutic method appears to be promising, since survival times of longer than 5 years have been achieved. Kitagawa and coworkers.!" referring to their patients with unresectable thymoma, mentioned that lesions infiltrating the SVC were responsible for poor prognosis. However, the prognosis may have been altered when these lesions were resected. ePTFE grafts have been reported to remain patent for 4 years by Garcia-Rinaldi and associates. I I Patency of an ePTFE graft was also demonstrated in one of our patients at 5 years. Such long-term patency relieves the symptoms of SVC syndrome and also may improve the prognosis for patients with invasive thymomas.
Conclusion Vascular reconstructions were performed in 20 patients: Fourteen had invasive thymoma, two had thymic Hodgkin's lymphoma, one had thymic non-Hodgkin's lymphoma, one had thymic carcinoma, one had thymic carcinoid tumor, and one had thymic seminoma. Six patients underwent only angioplasty, whereas artificial grafts were used in 14 patients. In only one of these patients were complications of the vascular operation or occlusive symptoms recognized postoperatively. Eight of
Surgery
the 16 patients are still alive. One is considered possibly cured since no signs of recurrence have been detected during a postoperative follow-up period of 8 years. REFERENCES 1. Bernatz PE, Khousari S, Harrison EG, Taylor WF. Thymoma: factors influencing prognosis. Surg Clin North Am 1973;53:885-91.
2. WilkinsEW, Cathleman B.Thymoma:a continuingsurvey at the Massachusetts General Hospital. Ann Thorac Surg 1979;28:252-6.
3. Fujimura S, Kondo T, Handa M, et al. Results of surgical treatment for thymoma based on 66 patients. J THoRAc CARDIOVASC SURG 1987;93:708-14. 4. LewislE, Wick MR, Scheithauer BW, Bernatz PE, et al. Thymoma: clinicopathological review. Cancer 1978;60: 2727-43.
5. Doty DB. Bypassof superior vena cava: six years' experience with spiral veingraft for obstruction of superiorvena cava due to benignand malignant disease. J THoRAc CARDIOVASC SURG 1982;83:326-38. 6. Doty DB, Doty JR, Jones KW. Bypass of superior vena cava: fifteen years' experience with spiral vein graft for obstructionof superiorvenacava caused by benigndisease. J THoRAc CARDIOVASC SURG 1990;99:889-96. 7. Tsubota N, Yamashita C, Ishii N, et al. The resultsof surgical treatment of invasive thymoma and thymus related tumors. Jpn J Thorac Surg 1985;86:752-61. 8. DartevelleP, Chapelier A, Navajas M, et al. Replacement of the superior vena cava with polytetrafluoroethylene grafts combined with resection of mediastinal-pulmonary malignant tumors. J THORAC CARDIOVASC SURG 1987; 94:361-6.
9. Shimizu N, Kurita A, Kunikata E, Hara F, YamamotoS, Teramoto S. The resultsof surgicaltreatment of thymoma. Rinsho Kyobu Geka 1983;3:424-9. 10. Kitagawa Y, Monden Y, Nakahara K, et al. The resultsof surgical treatment of 117 patients with thymoma. Jpn J Thorac Surg 1984;32:72-7. 11. Garcia-Rinaldi R, Zamora JL, Torres-Salichs M, et al. Four-year patencyof PTFE grafts after replacementof the superiorvenacavaand the innominateveins.Tex Heart Inst J 1988;15:192-4.