- Email: [email protected]
Surgical Treatment of Recurrent Thymomas
MALIGNANCIES
OF THE
THYMUS
Surgical Treatment of Recurrent Thymomas Marco Lucchi, MD,* and Alfredo Mussi, MD*
Abstract: Thymomas are neoplasms arising from the epithelial thymic cells, with a recurrence rate after complete resection ranging from 5 to 50%, according to the initial stage of disease. The pleura is the most frequent site of relapse, while distant metastases occur in less than 5% of the cases. Data in the literature show that recurrences can occur several years after the resection of a thymoma; unfortunately, few reports have analyzed the treatment of recurrences of thymoma. There is no standard treatment for the recurrent disease, and most of the treatments proposed by the authors are based more on their personal experience and individualized treatment than on an evidence-based method. Moreover, most series concerning surgery for recurrent thymomas suffer from a selection bias: patients with limited disease and better performance status are usually selected for surgery, with an anticipated survival advantage in the surgical group. Surgery for recurrent thymoma is indicated if complete resection is feasible, whereas in the case of predicted debulking surgery, it may be considered as part of a multidisciplinary protocol. In the literature, a few case reports of the surgical treatment of metachronous distant metastases to liver or brain from thymoma have been described, but they are really rare, and a decision about their treatment is always on a single patient basis. We can conclude that reoperation for thymoma recurrences is feasible and relatively safe, and it should always be considered because the other treatment modalities are not curative. Key Words: Thymoma, Multimodality treatments, Metastasis, Pleural relapse, Surgery, Chemotherapy, Survival.
Stage of disease is the major prognostic factor7 and is also the World Health Organization’s histologic classification.8 B2 and B3 thymomas should be considered at higher risk of relapse. If the primary resection was not radical, as can happen for some invasive thymomas and stage IVA, the definition of recurrence may not be appropriate. The invasion of great vessels and the size of the thymoma have been described as additional prognostic factors.9 In the literature, the largest series on the surgical treatment of recurrent thymomas are small series obtained by adding up all types of recurrences; common findings in these series is a long mean interval to recurrence.5,6,10,11 Local recurrence can be considered as a failure of the surgical treatment, and many consider adjuvant radiotherapy as potentially able to prevent local recurrence. Unfortunately, in stage II, the results are controversial,12 with most reports showing no benefit or a detrimental effect.13 Even stage III radiotherapy failed to give clear benefits in terms of diseasefree and overall survival.14 At the present time, the mostly accepted indications to adjuvant radiotherapy are: Y
Y Y
Resection performed macroscopically or microscopically not radical, particularly in case of thymomas, peeled off the phrenic nerve or great vessels. In case of any doubts about radicality of the resection, type B2/3, because it is more aggressive. In case of biopsies through mediastinotomy.
(J Thorac Oncol. 2010;5: S348–S351)
I
f thymoma is rare, recurrences from resected thymomas are even rarer.1,2 Different treatments have been reported, most as case reports.3,4 Selection bias is a major issue, because there is no evidence-based method and, overall, the literature is poor.5,6 The pattern of recurrence of resected thymomas includes local recurrence, pleural implants, and systemic metastases. The incidence ranges from 5 to 50% and is related to the initial stage of disease. *Division of Thoracic Surgery, Cardiac and Thoracic Department, University of Pisa, Italy. Disclosure: The authors declare no conflicts of interest. Address correspondence to: Marco Lucchi, MD, Division of Thoracic Surgery, Cardiac and Thoracic Department, University of Pisa, Via Paradisa 2, Pisa 56124, Italy. E-mail: [email protected] Copyright © 2010 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/10/0510-0348
S348
In our opinion, in some instances, when a thymoma is resected by means of mini-invasive procedures (VATS and/or robot), radicality can be compromised. These procedures proved to be feasible in case of thymomas; however, some major concerns still exist about the oncological propriety. Above all, in case of thymomas greater than 2 cm and without fat tissue surrounding the thymic capsule, the manipulation of the tumor may cause seeding of tumor cells that are responsible for local and pleural recurrences. We have already experienced one case of local relapse (Fig. 1) and two cases of pleural implants after the resection of early-stage thymomas by VATS. Usually local recurrences are approached through a resternotomy or a hemi clamshell or clamshell approach, according to the surgeon’s preference. These are usually difficult operations because of the adhesions caused by the previous operation and the adhesion/infiltrations with the phrenic nerves and great vessels. The complete resection rate is usually low, about 50 to 60%,5,6,10 but considering that adjuvant radiotherapy has mostly already been given after the
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010 Surgical Treatment of Recurrent Thymomas
Sometimes pleural recurrences are extensive, with huge pleural implants infiltrating the lung and the diaphragm; in such cases, an extended pleuropneumonectomy, usually reserved to malignant mesothelioma, and already proposed by Wright17 for the treatment of advanced stage IVA thymoma and pleural relapse, may be the only chance to attempt radicality. An attractive treatment of the pleural implants of thymoma is hyperthermic intrapleural chemotherapy. Refaely et al.18 described 15 cases of thymic malignancies with pleural spread, six of them were recurrent disease, treated by resection and hyperthermic intrapleural chemotherapy. The treatment was feasible and achieved an excellent local control. We also have experience with this technique and treated our last seven cases of pleural recurrences by resection and hyperthermic intrapleural perfusion with two drugs (cisplatin and doxorubicin) for 1 hour at 41 to 42°C. Recently, we reviewed and published our institutional experience on the surgical treatment of pleural recurrences of thymoma.11 In an update of our experience of the surgical resection of all the recurrences of thymoma, we identified 34 patients. There were two local relapses, two liver metastases, two peritoneal metastases, and 28 pleural implants.
FIGURE 1. Chest CT (A) of a 36-year-old woman who was operated on in another institution for a stage II B3 thymoma by left VATS and who experienced 2 years later a recurrence in the chest wall near the thymoma. She underwent resection of the recurrence en bloc with 2 ribs (B).
thymoma resection, surgery is the only local treatment available in a multimodality setting. Pleural relapse is more frequent. It accounts for less than 10% of resected thymomas,11 but they represent about 75% of the overall recurrences.10 It is not clear whether they are related to the particular biology of the tumor or whether they are consequences of seeding of the tumor, possibly determined by disruption of the capsule during the operation. For this reason, some surgeons recommend to avoid opening the mediastinal pleura and avoid miniinvasive procedures with a transpleural approach (thoracotomy, VATS, or robot assisted).15,16 Pleural recurrences are sometimes single and usually in the vertebral douche, near the diaphragm; more frequently, they are multiple, sometimes along the mediastinal pleura. Often the diaphragm is involved; in such case, a partial resection is necessary, and the deficit can be sutured with nonabsorbable single stitches.
FIGURE 2. CT showing pleural (A) and transdiaphragmatic retroperitoneal (B) metastasis.
Copyright © 2010 by the International Association for the Study of Lung Cancer
S349
Lucchi and Mussi
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010
FIGURE 3. CT showing a pulmonary metastasis on the right and thoracoplasty-like effect on the left (A). A huge peritoneal metastasis surrounding the spleen, dislocating the stomach and the kidney (B). The resection of the peritoneal mass en bloc with the spleen (C).
Most of the patients (n ⫽ 20) had an initial stage III thymoma, and the median interval between the resection of the thymoma and the recurrence was 55 months. A thymusrelated syndrome was present in 21 cases, mostly myasthenia gravis. Four patients underwent repeat resections of pleural implants. The overall perioperative mortality was nil and morbidity was mild. Focusing on the cases of pleural recurrence, the majority of patients had multiple implants and 10 cases showed a diaphragmatic involvement. With an update of the recently published series,11 overall 5- and 10-year survivals from the pleural recurrence resection were 44.7 and 27.1%, respectively. Comparing the survival of the single metastasis group with the multiple metastases, we found that single metastasis had a statistically significant better survival than multiple metastases. Moreover, patients with diaphragmatic involvement showed a significantly worse prognosis. Transdiaphragmatic retroperitoneal metastasis can occur at diagnosis or after a resection of pleural relapse.19 We also identified two such cases (Fig. 2) and decided to approach simultaneously the resection of the pleural implants
S350
by a thoracotomy and the peritoneal implants by a lumbotomy or a laparotomy. It can be expected, similarly to what occurs with malignant pleural mesothelioma after an extended pleuropneumonectomy, that after the resection of pleural implants involving the diaphragm, peritoneal implants will be experienced. With a longer follow-up, the incidence of peritoneal implants will increase, and there will be a surgical challenge. Sometimes, we face advanced metastatic thymoma, and surgeons, oncologists, or radiotherapists do not have good arms to treat these patients. Particularly, surgery does not seem to play any role when the disease is systemic, but some dramatically unconventional cases require a multidisciplinary evaluation and the exploration of new treatments. As an example, 2 years ago, we treated a 32-year-old man who had undergone a multimodality treatment (neoadjuvant chemotherapy, surgery, and adjuvant radiotherapy) in 2002 for an invasive stage III thymoma. In May 2004, he had multiple pleural implants treated by six courses of a secondline chemotherapy and then somatostatin LAR and prednisone. In 2006, a pleurectomy plus partial diaphragmatic
Copyright © 2010 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010 Surgical Treatment of Recurrent Thymomas
resection and hyperthermic chemotherapy with doxorubicin were performed at another institution. Then, the patient underwent radiotherapy on the chest wall and single drug chemotherapy. In 2007, there was pleural and peritoneal progression. In April 2008, he was referred to our center with a chest computed tomography showing a pulmonary metastasis on the right and thoracoplasty-like effect on the left, a huge peritoneal metastasis surrounding the spleen, dislocating the stomach and the kidney (Figure 3). On the right lobe of the liver, there was a peritoneal mass that was defined as a liver metastasis at preoperative staging. A suspicion of lumbar vertebral metastasis was also present. We decided to enroll the patient in a phase I study of radioimmuno therapy, debulking of the peritoneal mass that caused major symptoms for the patient at that time (Figure 3). We removed the mass en bloc with the spleen and also a lot of peritoneal implants. It was not a liver metastasis but a peritoneal implant compressing the liver. On the surgical specimen, we studied the extradomain  of fibronectin, an oncofetal antigen expressed at various levels in the stroma of a large variety of neoplastic tissues, and we found it to be highly expressed. In such cases, surgery is mainly to palliate symptoms and to provide tissue for a biologic characterization necessary for target therapies. The treatment of distant metastasis from thymoma, synchronous or metachronous, should be discussed in a multimodality setting and on a single patient basis. In the literature, a few case reports of resection of single distant metastasis have been described with good results.20,21 We also had two patients who underwent resection of metachronous single-liver metastasis, resulting in long-term survival (63 and 89 months, respectively, from the liver resection). Obviously, surgery should not be proposed to all patients with distant metastases of thymoma, but whenever metastases are single or easily resectable or with a long disease-free interval, surgical resection should be considered. So we can conclude that reoperation and also rereoperation of thymoma recurrences are feasible and safe. It allows a good overall survival and paraneoplastic syndrome control. REFERENCES 1. Kondo K, Monden Y. Lymphogenous and hematogenous metastasis of thymic epithelial tumours. Ann Thorac Surg 2003;76:1859 –1864.
2. Haniuda M, Kondo R, Numanami H, et al. Recurrence of thymoma: clinicopathological features, re-operation, and outcome. J Surg Oncol 2001;78:183–188. 3. Taguchi T, Suehiro T, Toru K, et al. Pleural dissemination of thymoma showing tumor regression after combined corticosteroid and tacrolimus therapy. Eur J Intern Med 2006;17:575–577. 4. Sakada T, Sugio K, Nishioka K, et al. Invasive thymoma with long-term survival by extensive reoperation. Respiration 1999;66:167–169. 5. Ruffini E, Mancuso M, Oliaro A, et al. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 1997;113:55– 63. 6. Regnard JF, Zinzindohoue F, Magdeleinat P, et al. Results of reresection for recurrent thymomas. Ann Thorac Surg 1997;64:1593– 1598. 7. Masaoka A, Monden Y, Nakahara K, et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48: 2485–2492. 8. Okumura M, Ohta M, Tateyama H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002;94:624 – 632. 9. Wright CD, Wain JC, Wong DR, et al. Predictors of recurrence in thymic tumors: importance of invasion, World Health Organization histology, and size. J Thorac Cardiovasc Surg 2005;130:1413–1421. 10. Ruffini E, Filosso PL, Oliaro A. The role of surgery in recurrent thymic tumors. Thorac Surg Clin 2009;19:121–31. 11. Lucchi M, Davini F, Ricciardi R, et al. Management of pleural recurrence after curative resection of thymoma. J Thorac Cardiovasc Surg 2009;137:1185–1189. 12. Cowen D, Richaud P, Mornex F, et al. Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fe´de´ration Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 1995;34:9 –16. 13. Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 2002;74:1033–1037. 14. Mangi AA, Wain JC, Donahue DM, et al. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg 2005;79:1834 –1839. 15. Maggi G, Casadio C, Cavallo A, et al. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991;51:152–156. 16. Regnard JF, Magdeleinat P, Dromer C, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996;112:376 –384. 17. Wright CD. Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma. Ann Thorac Surg 2006;82:1234 –1239. 18. Refaely Y, Simansky DA, Paley M, et al. Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread. Ann Thorac Surg 2001;72:366 –370. 19. Debnath J, Chawla N, Talwar R, et al. Pleural and transdiaphragmatic retroperitoneal metastasis developing two and half years after resection of invasive thymoma. Singapore Med J 2008;49:64 – 67. 20. Moretti R, Nasuelli D, Torre P, et al. Hepatic metastasis of thymoma. Eur J Neurol 2000;7:127–128. 21. Jose B, Yu AT, Morgan TF, et al. Malignant thymoma with extrathoracic metastasis: a case report and review of literature. J Surg Oncol 1980;15:259 –263.
Copyright © 2010 by the International Association for the Study of Lung Cancer
S351
OF THE
THYMUS
Surgical Treatment of Recurrent Thymomas Marco Lucchi, MD,* and Alfredo Mussi, MD*
Abstract: Thymomas are neoplasms arising from the epithelial thymic cells, with a recurrence rate after complete resection ranging from 5 to 50%, according to the initial stage of disease. The pleura is the most frequent site of relapse, while distant metastases occur in less than 5% of the cases. Data in the literature show that recurrences can occur several years after the resection of a thymoma; unfortunately, few reports have analyzed the treatment of recurrences of thymoma. There is no standard treatment for the recurrent disease, and most of the treatments proposed by the authors are based more on their personal experience and individualized treatment than on an evidence-based method. Moreover, most series concerning surgery for recurrent thymomas suffer from a selection bias: patients with limited disease and better performance status are usually selected for surgery, with an anticipated survival advantage in the surgical group. Surgery for recurrent thymoma is indicated if complete resection is feasible, whereas in the case of predicted debulking surgery, it may be considered as part of a multidisciplinary protocol. In the literature, a few case reports of the surgical treatment of metachronous distant metastases to liver or brain from thymoma have been described, but they are really rare, and a decision about their treatment is always on a single patient basis. We can conclude that reoperation for thymoma recurrences is feasible and relatively safe, and it should always be considered because the other treatment modalities are not curative. Key Words: Thymoma, Multimodality treatments, Metastasis, Pleural relapse, Surgery, Chemotherapy, Survival.
Stage of disease is the major prognostic factor7 and is also the World Health Organization’s histologic classification.8 B2 and B3 thymomas should be considered at higher risk of relapse. If the primary resection was not radical, as can happen for some invasive thymomas and stage IVA, the definition of recurrence may not be appropriate. The invasion of great vessels and the size of the thymoma have been described as additional prognostic factors.9 In the literature, the largest series on the surgical treatment of recurrent thymomas are small series obtained by adding up all types of recurrences; common findings in these series is a long mean interval to recurrence.5,6,10,11 Local recurrence can be considered as a failure of the surgical treatment, and many consider adjuvant radiotherapy as potentially able to prevent local recurrence. Unfortunately, in stage II, the results are controversial,12 with most reports showing no benefit or a detrimental effect.13 Even stage III radiotherapy failed to give clear benefits in terms of diseasefree and overall survival.14 At the present time, the mostly accepted indications to adjuvant radiotherapy are: Y
Y Y
Resection performed macroscopically or microscopically not radical, particularly in case of thymomas, peeled off the phrenic nerve or great vessels. In case of any doubts about radicality of the resection, type B2/3, because it is more aggressive. In case of biopsies through mediastinotomy.
(J Thorac Oncol. 2010;5: S348–S351)
I
f thymoma is rare, recurrences from resected thymomas are even rarer.1,2 Different treatments have been reported, most as case reports.3,4 Selection bias is a major issue, because there is no evidence-based method and, overall, the literature is poor.5,6 The pattern of recurrence of resected thymomas includes local recurrence, pleural implants, and systemic metastases. The incidence ranges from 5 to 50% and is related to the initial stage of disease. *Division of Thoracic Surgery, Cardiac and Thoracic Department, University of Pisa, Italy. Disclosure: The authors declare no conflicts of interest. Address correspondence to: Marco Lucchi, MD, Division of Thoracic Surgery, Cardiac and Thoracic Department, University of Pisa, Via Paradisa 2, Pisa 56124, Italy. E-mail: [email protected] Copyright © 2010 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/10/0510-0348
S348
In our opinion, in some instances, when a thymoma is resected by means of mini-invasive procedures (VATS and/or robot), radicality can be compromised. These procedures proved to be feasible in case of thymomas; however, some major concerns still exist about the oncological propriety. Above all, in case of thymomas greater than 2 cm and without fat tissue surrounding the thymic capsule, the manipulation of the tumor may cause seeding of tumor cells that are responsible for local and pleural recurrences. We have already experienced one case of local relapse (Fig. 1) and two cases of pleural implants after the resection of early-stage thymomas by VATS. Usually local recurrences are approached through a resternotomy or a hemi clamshell or clamshell approach, according to the surgeon’s preference. These are usually difficult operations because of the adhesions caused by the previous operation and the adhesion/infiltrations with the phrenic nerves and great vessels. The complete resection rate is usually low, about 50 to 60%,5,6,10 but considering that adjuvant radiotherapy has mostly already been given after the
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010 Surgical Treatment of Recurrent Thymomas
Sometimes pleural recurrences are extensive, with huge pleural implants infiltrating the lung and the diaphragm; in such cases, an extended pleuropneumonectomy, usually reserved to malignant mesothelioma, and already proposed by Wright17 for the treatment of advanced stage IVA thymoma and pleural relapse, may be the only chance to attempt radicality. An attractive treatment of the pleural implants of thymoma is hyperthermic intrapleural chemotherapy. Refaely et al.18 described 15 cases of thymic malignancies with pleural spread, six of them were recurrent disease, treated by resection and hyperthermic intrapleural chemotherapy. The treatment was feasible and achieved an excellent local control. We also have experience with this technique and treated our last seven cases of pleural recurrences by resection and hyperthermic intrapleural perfusion with two drugs (cisplatin and doxorubicin) for 1 hour at 41 to 42°C. Recently, we reviewed and published our institutional experience on the surgical treatment of pleural recurrences of thymoma.11 In an update of our experience of the surgical resection of all the recurrences of thymoma, we identified 34 patients. There were two local relapses, two liver metastases, two peritoneal metastases, and 28 pleural implants.
FIGURE 1. Chest CT (A) of a 36-year-old woman who was operated on in another institution for a stage II B3 thymoma by left VATS and who experienced 2 years later a recurrence in the chest wall near the thymoma. She underwent resection of the recurrence en bloc with 2 ribs (B).
thymoma resection, surgery is the only local treatment available in a multimodality setting. Pleural relapse is more frequent. It accounts for less than 10% of resected thymomas,11 but they represent about 75% of the overall recurrences.10 It is not clear whether they are related to the particular biology of the tumor or whether they are consequences of seeding of the tumor, possibly determined by disruption of the capsule during the operation. For this reason, some surgeons recommend to avoid opening the mediastinal pleura and avoid miniinvasive procedures with a transpleural approach (thoracotomy, VATS, or robot assisted).15,16 Pleural recurrences are sometimes single and usually in the vertebral douche, near the diaphragm; more frequently, they are multiple, sometimes along the mediastinal pleura. Often the diaphragm is involved; in such case, a partial resection is necessary, and the deficit can be sutured with nonabsorbable single stitches.
FIGURE 2. CT showing pleural (A) and transdiaphragmatic retroperitoneal (B) metastasis.
Copyright © 2010 by the International Association for the Study of Lung Cancer
S349
Lucchi and Mussi
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010
FIGURE 3. CT showing a pulmonary metastasis on the right and thoracoplasty-like effect on the left (A). A huge peritoneal metastasis surrounding the spleen, dislocating the stomach and the kidney (B). The resection of the peritoneal mass en bloc with the spleen (C).
Most of the patients (n ⫽ 20) had an initial stage III thymoma, and the median interval between the resection of the thymoma and the recurrence was 55 months. A thymusrelated syndrome was present in 21 cases, mostly myasthenia gravis. Four patients underwent repeat resections of pleural implants. The overall perioperative mortality was nil and morbidity was mild. Focusing on the cases of pleural recurrence, the majority of patients had multiple implants and 10 cases showed a diaphragmatic involvement. With an update of the recently published series,11 overall 5- and 10-year survivals from the pleural recurrence resection were 44.7 and 27.1%, respectively. Comparing the survival of the single metastasis group with the multiple metastases, we found that single metastasis had a statistically significant better survival than multiple metastases. Moreover, patients with diaphragmatic involvement showed a significantly worse prognosis. Transdiaphragmatic retroperitoneal metastasis can occur at diagnosis or after a resection of pleural relapse.19 We also identified two such cases (Fig. 2) and decided to approach simultaneously the resection of the pleural implants
S350
by a thoracotomy and the peritoneal implants by a lumbotomy or a laparotomy. It can be expected, similarly to what occurs with malignant pleural mesothelioma after an extended pleuropneumonectomy, that after the resection of pleural implants involving the diaphragm, peritoneal implants will be experienced. With a longer follow-up, the incidence of peritoneal implants will increase, and there will be a surgical challenge. Sometimes, we face advanced metastatic thymoma, and surgeons, oncologists, or radiotherapists do not have good arms to treat these patients. Particularly, surgery does not seem to play any role when the disease is systemic, but some dramatically unconventional cases require a multidisciplinary evaluation and the exploration of new treatments. As an example, 2 years ago, we treated a 32-year-old man who had undergone a multimodality treatment (neoadjuvant chemotherapy, surgery, and adjuvant radiotherapy) in 2002 for an invasive stage III thymoma. In May 2004, he had multiple pleural implants treated by six courses of a secondline chemotherapy and then somatostatin LAR and prednisone. In 2006, a pleurectomy plus partial diaphragmatic
Copyright © 2010 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 5, Number 10, Supplement 4, October 2010 Surgical Treatment of Recurrent Thymomas
resection and hyperthermic chemotherapy with doxorubicin were performed at another institution. Then, the patient underwent radiotherapy on the chest wall and single drug chemotherapy. In 2007, there was pleural and peritoneal progression. In April 2008, he was referred to our center with a chest computed tomography showing a pulmonary metastasis on the right and thoracoplasty-like effect on the left, a huge peritoneal metastasis surrounding the spleen, dislocating the stomach and the kidney (Figure 3). On the right lobe of the liver, there was a peritoneal mass that was defined as a liver metastasis at preoperative staging. A suspicion of lumbar vertebral metastasis was also present. We decided to enroll the patient in a phase I study of radioimmuno therapy, debulking of the peritoneal mass that caused major symptoms for the patient at that time (Figure 3). We removed the mass en bloc with the spleen and also a lot of peritoneal implants. It was not a liver metastasis but a peritoneal implant compressing the liver. On the surgical specimen, we studied the extradomain  of fibronectin, an oncofetal antigen expressed at various levels in the stroma of a large variety of neoplastic tissues, and we found it to be highly expressed. In such cases, surgery is mainly to palliate symptoms and to provide tissue for a biologic characterization necessary for target therapies. The treatment of distant metastasis from thymoma, synchronous or metachronous, should be discussed in a multimodality setting and on a single patient basis. In the literature, a few case reports of resection of single distant metastasis have been described with good results.20,21 We also had two patients who underwent resection of metachronous single-liver metastasis, resulting in long-term survival (63 and 89 months, respectively, from the liver resection). Obviously, surgery should not be proposed to all patients with distant metastases of thymoma, but whenever metastases are single or easily resectable or with a long disease-free interval, surgical resection should be considered. So we can conclude that reoperation and also rereoperation of thymoma recurrences are feasible and safe. It allows a good overall survival and paraneoplastic syndrome control. REFERENCES 1. Kondo K, Monden Y. Lymphogenous and hematogenous metastasis of thymic epithelial tumours. Ann Thorac Surg 2003;76:1859 –1864.
2. Haniuda M, Kondo R, Numanami H, et al. Recurrence of thymoma: clinicopathological features, re-operation, and outcome. J Surg Oncol 2001;78:183–188. 3. Taguchi T, Suehiro T, Toru K, et al. Pleural dissemination of thymoma showing tumor regression after combined corticosteroid and tacrolimus therapy. Eur J Intern Med 2006;17:575–577. 4. Sakada T, Sugio K, Nishioka K, et al. Invasive thymoma with long-term survival by extensive reoperation. Respiration 1999;66:167–169. 5. Ruffini E, Mancuso M, Oliaro A, et al. Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 1997;113:55– 63. 6. Regnard JF, Zinzindohoue F, Magdeleinat P, et al. Results of reresection for recurrent thymomas. Ann Thorac Surg 1997;64:1593– 1598. 7. Masaoka A, Monden Y, Nakahara K, et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48: 2485–2492. 8. Okumura M, Ohta M, Tateyama H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002;94:624 – 632. 9. Wright CD, Wain JC, Wong DR, et al. Predictors of recurrence in thymic tumors: importance of invasion, World Health Organization histology, and size. J Thorac Cardiovasc Surg 2005;130:1413–1421. 10. Ruffini E, Filosso PL, Oliaro A. The role of surgery in recurrent thymic tumors. Thorac Surg Clin 2009;19:121–31. 11. Lucchi M, Davini F, Ricciardi R, et al. Management of pleural recurrence after curative resection of thymoma. J Thorac Cardiovasc Surg 2009;137:1185–1189. 12. Cowen D, Richaud P, Mornex F, et al. Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fe´de´ration Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 1995;34:9 –16. 13. Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 2002;74:1033–1037. 14. Mangi AA, Wain JC, Donahue DM, et al. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg 2005;79:1834 –1839. 15. Maggi G, Casadio C, Cavallo A, et al. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991;51:152–156. 16. Regnard JF, Magdeleinat P, Dromer C, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996;112:376 –384. 17. Wright CD. Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma. Ann Thorac Surg 2006;82:1234 –1239. 18. Refaely Y, Simansky DA, Paley M, et al. Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread. Ann Thorac Surg 2001;72:366 –370. 19. Debnath J, Chawla N, Talwar R, et al. Pleural and transdiaphragmatic retroperitoneal metastasis developing two and half years after resection of invasive thymoma. Singapore Med J 2008;49:64 – 67. 20. Moretti R, Nasuelli D, Torre P, et al. Hepatic metastasis of thymoma. Eur J Neurol 2000;7:127–128. 21. Jose B, Yu AT, Morgan TF, et al. Malignant thymoma with extrathoracic metastasis: a case report and review of literature. J Surg Oncol 1980;15:259 –263.
Copyright © 2010 by the International Association for the Study of Lung Cancer
S351