ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Ann Thorac Surg 2008;86:673-684. doi:10.1016/j.athoracsur.2008.03.055
© 2008 The Society of Thoracic Surgeons
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Richard A. Malthaner
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Davenport, E.
Right arrow Articles by Malthaner, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davenport, E.
Right arrow Articles by Malthaner, R. A.
Related Collections
Right arrow Mediastinum

Review

The Role of Surgery in the Management of Thymoma: A Systematic Review

Eric Davenport, MD, Richard A. Malthaner, MD, MS*

Division of Thoracic Surgery, Department of Surgery, The University of Western Ontario, London, Ontario, Canada

* Address correspondence to Dr Malthaner, London Health Sciences Centre, 800 Commissioners Rd E, Suite E2-124, London, Ontario, N6A 5W9, Canada (Email: richard.malthaner{at}lhsc.on.ca).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
The literature describing multimodal treatment of thymomas consists almost exclusively of retrospective case series. We have used a systematic review to investigate the role of surgery in the management of thymomas. The use of surgery as the sole therapeutic maneuver in thymoma depends on the stage considered. Subtotal resection followed by adjuvant treatment may prolong survival, but studies are equivocal. Some data supports re-resection of recurrent thymoma in the belief that survival will be prolonged. Approaches to thymectomy other than sternotomy in early stage thymoma are technically sound, but long-term outcome data are lacking.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Thymomas are very rare tumors of the thymus gland. Recent reports have demonstrated incidence estimates of 0.15 per 100,000 person years in the United States [1]. Thymomas are typically slow-growing tumors that spread by local extension. Metastases are usually confined to the pleura, pericardium, or diaphragm, whereas extrathoracic metastases are uncommon [2, 3]. Thymomas are also known to have a propensity for late recurrence even after complete resection [4, 5].

Histopathologically, thymomas are primary tumors of thymic epithelial cells [6]. Thymic carcinoids and thymic carcinomas are also tumors of thymic epithelial cells. Thymic carcinoids are histopathologically and clinically quite different from thymomas [7–9]. On the other hand, the distinction between thymomas and thymic carcinomas has been somewhat controversial. Thymomas are for the most part considered cytologically benign. Thymic carcinoma is meant to describe that category of thymic epithelial cell tumors with malignant cytologic features [6, 10]. The World Health Organization histopathologic classification of thymomas is the most recent, and it has been validated in several studies [11–13]. It describes thymoma and thymic carcinoma along a continuum. Studies have demonstrated markedly decreased survival for thymic carcinoma compared with thymoma [14–19]. Thymic carcinoma may therefore be treated as a distinct pathologic and prognostic entity.

The most widely used staging system for thymomas is that published by Masaoka and colleagues [20] in 1981. Their publication describes thymomas in terms of local extension of the tumor (see Table 1). It has been shown to predict survival in several studies [11, 21–27]. Investigators have begun to describe the molecular changes that confer differing degrees of invasiveness and their relationship to the Masaoka staging system [28–30]. The Masaoka staging system is a particularly useful tool in studies of thymoma, given the rarity and histopathologic heterogeneity of this tumor.


View this table:
[in this window]
[in a new window]

  		Table 1 Masoaka Staging System
 
Patients with thymomas present with symptoms related to involvement of local structures or as asymptomatic findings on imaging of the chest. The most common presenting symptoms for thymomas are dyspnea, chest pain, cough, and symptoms of myasthenia gravis [31–34]. Superior vena cava syndrome is not an unusual presentation for the patient with stage III or IV thymoma [35, 36]. Thymomas are frequently associated with paraneoplastic phenomena and as a consequence that can have quite varied presentations [37–39].

The incidence of thymomas is increased in patients with myasthenia gravis (MG). Approximately 10% of patients with MG will have a thymoma [40–42]. Some authors have proposed that MG is an adverse prognostic factor for patients undergoing resection of thymoma because of the increased perioperative mortality, typically secondary to myasthenic respiratory failure [34]. Other authors have argued that MG is a positive prognostic factor, possibly because of earlier diagnosis of thymoma [11, 16, 43]. Some case series have shown that the presence of MG has no effect on survival from thymoma, and the authors attribute this finding to improvements in the perioperative management of MG [3, 24, 44–47]. The perioperative care of the MG patient undergoing thymectomy has been the subject of a recent review [48].

The treatment of thymomas involves combinations of surgery, radiation, and chemotherapy. The determination of which combination is chosen is reflected mostly by the stage of the disease. In the case of invasive disease, radiation therapy is often used as adjuvant treatment. Chemotherapy has been used in the induction and adjuvant setting. The interested reader may refer to a systematic review on the role of radiation and chemotherapy in thymoma by Hejna and colleagues [49].

Numerous reviews on the surgical treatment of thymomas have been published [50–65]. The reviews present either a single-centre case series or provide opinions based on a nonsystematic analysis of the literature. We believe that an evidence-based recommendation on the role of surgery in thymoma has not yet been published. Any review of thymoma will be complicated by its rarity, confusion surrounding its histopathologic classification, and its propensity for late recurrence. We have developed an evidence-based recommendation on the role of surgery in thymoma using reproducible inclusion and exclusion criteria. It was not the aim of our study to address the evidence supporting the role of radiation therapy in the management of thymoma. However, we have included literature that purports to describe the adequacy of surgery alone in the management of thymoma, and this inevitably leads to outcome comparisons with patients who have received adjuvant radiation. We have not addressed the role of chemotherapy either in the induction or adjuvant setting.

We have sought to answer several questions related to surgical intervention. First, is there evidence to support the use of surgery as the sole therapeutic maneuver in the management of thymoma? Second, does incomplete resection for thymomas (so-called debulking surgery) increase overall survival? Third, is surgery a useful modality in the treatment of recurrent thymoma? We have also reviewed the various surgical approaches used to achieve resection of thymoma. We articulated our treatment recommendations using the framework put forth by Guyatt and colleagues [66]. These are shown in Table 2.


View this table:
[in this window]
[in a new window]

  		Table 2 Levels of Treatment Recommendations
 

   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Literature Search Strategy
A search of the MEDLINE database was performed with the keywords "thymoma" and "surgery" using the following limits: English language only, humans only, and published after 1981 (the year in which the Masaoka staging system was published). The Cochrane database, the National Guideline Clearinghouse (http://www.guideline.gov/index.asp) and abstracts from the 2004 and 2007 American Association of Thoracic Surgery meetings were also searched for English language abstracts or manuscripts related to thymomas. The final literature search was performed on June 26, 2007.

Inclusion Criteria
We included any prospective, randomized trial dealing with thymoma regardless of language publication. We included any English language retrospective series describing surgical intervention in patients with thymoma, including those describing patients undergoing re-resection for thymoma recurrence. We included articles in which the focus of the article was a description of one or more operative approaches to thymectomy in thymoma.

Exclusion Criteria
The following were excluded from analysis:

• Case series of fewer than 40 patients (unless the article dealt specifically with minimally invasive surgical approaches to thymectomy).
• Articles in which the focus was basic science, pathology, biochemistry, or radiology.
• Articles describing chemotherapy protocols or the response to radiation (if no description of the effects of surgery on survival was given).
• Articles with no 5-year survival data and those in which the Masaoka stage was not used.
• Articles dealing solely with thymic carcinoids or thymic carcinoma and those in which thymoma, thymic carcinoma, or other mediastinal tumors were pooled in outcome determinations, or a combination thereof.
• Articles in which myasthenia gravis was the focus of the study. This led to exclusion of articles in which thymomas were present in the series of myasthenic patients, but in which the outcome measures focused on myasthenic phenomena.
• Letters and editorials reporting trial data.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Literature Search Results
Our search strategy yielded 616 abstracts. Using our selection criteria we recovered a single prospective, randomized controlled trial and 23 retrospective series with between 40 and 1,093 patients. The patients in these studies were subjected to various combinations of surgery, radiotherapy, and chemotherapy. Patients within and between studies were very heterogeneous with respect to treatment protocols. Several small case series of between 1 and 22 patients were used in our discussion of surgical approaches to thymectomy.

Influence of Surgical Resection on Survival
The stage-specific survival, operative mortality and morbidity, and overall survival effects of surgical resection for thymomas from several retrospective studies [3, 11, 18, 21, 22, 25–27, 45, 47, 68, 70, 88–92] are shown in Table 3.


View this table:
[in this window]
[in a new window]

  		Table 3 Overall Survival Effects of Complete Resection in Thymoma, Retrospective Case Series Evidence
 
The studies described in Table 3 involved a wide range of treatment approaches, making it prohibitively difficult to correlate specific multimodality treatment regimens with survival. The types of treatment received by the patients in each study are nonetheless listed. Operative mortality was reported in 7 studies. In 3 studies (with a total of 151 patients) there were no operative mortalities. Operative mortality in the other studies was mostly due to myasthenic crisis and cardiac causes. For stage I, the 5-year survival ranged from 89% to 100% and the 10-year survival ranged from 87% to 100%. For stage II, the 5-year survival ranged from 71% to 95% and the 10-year survival ranged from 60% to 100%. For stage III, the 5-year survival ranged from 59% to 75% and the 10-year survival ranged from 47% to 88%. In the case of stage IVA disease, the 5-year survival ranged from 34% to 71% and the 10-year survival ranged from 30% to 40%. For stage IVB disease, only two studies reported the 5-year survival, and this ranged from 0% to 53%. The latter value of 53% was obtained from the study by Kondo and colleagues [18], which was in fact a questionnaire with a 62% response rate making it quite possible that substantial reporting bias is present.

Data on Surgery as the Sole Therapeutic Maneuver
The only prospective randomized trial was a study of 29 patients with completely resected stage I thymomas who were randomized to a group receiving no adjuvant treatment (n = 13) and a group receiving adjuvant radiation (n = 16). All patients underwent resection through a median sternotomy. The authors found no difference in 5-year and 10-year survival between the two groups. In addition, there was no recurrence or metastasis in either group [67].

The studies [71, 72, 93] summarized in Table 4 reveal that complete resection of thymoma is a statistically significant predictor of 5-year survival. This was seen to apply to stages I, II, and III. In several studies authors described resection of the pleura, lung, pericardium, and venous structures to achieve complete resection. In only two studies, the extent of resection was not a predictor of overall survival [25, 68]. In one of these, the authors found that invasion of the great vessels (ie, the aorta, vena cava, brachiocephalic vein) was the factor that predicted overall survival [25].


View this table:
[in this window]
[in a new window]

  		Table 4 Surgery as the Sole Modality in Thymoma, Retrospective Case Series Evidence
 
Only three retrospective series specifically focused on the role of surgery with or without adjuvant radiation; these are summarized in Table 4. They reveal that mortality in completely resected stage I and II thymoma is the same whether or not adjuvant radiation is added. In neither study was adjuvant chemotherapy used. A single study of stage III patients did not demonstrate a survival benefit to the addition of radiation therapy.

The Role of De-Bulking Surgery
Table 5 summarizes six retrospective series [3, 11, 18, 26, 45, 94] that have addressed the role of de-bulking surgery in thymoma. Four of the studies reveal improvement in overall 5-year survival of approximately 30% for the patient who undergoes subtotal resection. Two other studies demonstrate no survival difference when de-bulking was used.


View this table:
[in this window]
[in a new window]

  		Table 5 Effects of Subtotal Resection for Thymoma, Retrospective Case Series
 
The Role of Re-Resection for Recurrent Thymoma
Six retrospective case series [4, 33, 75, 76, 95, 96] dealing with the role of re-resection in recurrent thymoma are summarized in Table 6. These studies were heterogeneous with respects to the sight of recurrence. At one extreme, the series reported by Haniuda and colleagues [23] revealed that 92% of recurrences consisted of pleural dissemination, whereas the other the series reported by Blumberg and colleagues [33] had 68% of recurrences occurring locally. In three of the six series there is no survival advantage conferred by debulking. In the two series that do show a 5-year survival of advantage of approximately 40% to 50%, the patients who underwent resection were almost exclusively patients with local recurrence.


View this table:
[in this window]
[in a new window]

  		Table 6 Reoperation for Recurrent Thymoma, Retrospective Case Series Evidence
 
The Surgical Approaches to Thymectomy in Thymoma
No abstracts or articles describing approaches to thymectomy other than sternotomy were found, which had greater than 40 patients or provided 5-year survival data. No formal analysis of these articles was undertaken.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
A significant limitation to generation of evidenced-based recommendations in the management of rare diseases is the paucity of prospective data on which to soundly base those recommendations. In the case of thymomas (with a single exception) all of the English language literature consists of retrospective case series with inconsistently applied treatment regimens. Notwithstanding the fact that surgeons may rarely encounter such diseases, treatment should be based on the best available evidence.

The role of thymectomy in nonthymomatous myasthenia gravis was the subject of a recent systematic review, but there are no other English language guidelines dealing with diseases of the thymus or thymectomy [69].

Completeness of resection is the most commonly cited statistically significant prognostic factor in thymoma. In the case of stage III disease, combinations of partial pleurectomy, pericardial resection, wedge resections of lung, lobectomy, pneumonectomy, resection of a single phrenic nerve, superior vena cava, and innominate vein surgeries have all been performed in series that have demonstrated improved survival for locally invading stage III disease treated with complete resection [21, 45, 70]. In a small number of cases, the survival benefit of complete resection also extended to stage IV thymomas [3, 26, 70].

The effect of complete resection in most of the series we reviewed was approximately a 50% increase in survival at 5 years. However, it must be emphasized that while this increase in survival is impressive, it is derived entirely from unblinded, uncontrolled retrospective case series. In the framework put forth by Guyatt and colleagues [66], the recommendation to pursue maximally aggressive resection in thymoma would be one with a clear effect (of enhancing survival), but backed by methodological, weak evidence.

The Role of Surgery as a Sole Therapeutic Maneuver
Four studies specifically addressed the role of surgery as the sole therapeutic modality in the management of thymomas. Prospective evidence from a single, small randomized trial exists for uniquely surgical treatment of stage I thymoma with no need for adjuvant treatment [67]. Further retrospective case series support the use of surgery only in the management of completely resected stage I and II disease [71, 72]. A single study showed no survival benefit to adjuvant radiation in stage III thymoma [73]. In none of these series were decisions to radiate driven by protocol, and thus significant selection bias is likely present. This was not an analysis of the role of radiotherapy in thymoma and many have recommended radiotherapy for thymomas of stage II and higher [11, 24, 26]. A prospective, randomized multicenter trial on the use of adjuvant radiation in stage I and II thymoma would be worthwhile, but it would be hindered by slow patient accrual and the need for long-term follow-up [4, 5].

The Role of Debulking Surgery
The literature we have reviewed does not convincingly demonstrate that incomplete resection (ie, debulking) increases survival in cases of invasive thymoma. Some authors report no survival advantage to debulking [18, 34, 45]. Others series have demonstrated approximately 30% increased 5-year survival with subtotal resection [11, 18, 26, 74]. Unfortunately, one of these studies is a questionnaire with a 62% response rate [18]. In addition, there is tremendous variability in the use of adjuvant treatments both within and between individual studies, making it impossible to draw sound conclusions on the role of debulking in thymoma. Debulking in thymoma is a surgical strategy for which the results are globally equivocal and the underlying data is very methodologically weak.

The Role of Re-Resection
Recurrence of thymoma after thymectomy is quite common. The largest reported series of 1,093 thymomas found recurrence rates for stages I, II, III, and IV were 0.9%, 4.1%, 28.4%, and 34.3%, respectively [18]. Series in which as much as 90% of the operative cases were because of local recurrence have shown that wherever possible re-resection improves survival [4, 33, 75]. Others surgeons have found that reoperation had no effect on survival or was no better than debulking [75, 76]. It is important to draw a distinction between local recurrences, to which virtually all of the survival benefit from re-resection applies, and intrathoracic pleural dissemination. Widely disseminated pleural disease is associated with a poor response to surgery.

From these data it would seem reasonable to consider re-resection of locally recurrent thymoma, but once again the data on which such a recommendation is based are methodologically weak. Recurrence of thymoma has been associated with very severe myasthenia gravis, and thus increased risk of operative mortality [75, 76].

Surgical Approaches to Thymectomy in Thymoma
In our literature review, there was not any 5-year survival outcomes reported for various surgical approaches to thymectomy for thymoma. Nonetheless, we chose to comment on this topic, as it is especially germane to the thrust of this article (ie, the role of surgery in the management of thymoma). The aim of surgery in thymoma is complete thymectomy as opposed to complete tumor excision, and this is supported by data demonstrating improved survival after complete thymectomy [34]. In all of the case series we have described thus far, median sternotomy was the most common surgical approach used.

Case reports attest to the possibility of performing thymectomy for stage I and II thymoma by video-assisted thoracoscopy [77–81]. The use of robotic surgery to resect stage I thymoma has recently been described [82]. Some authors have raised concerns about minimally invasive approaches to thymomectomy for thymoma, in particular capsular rupture with its risk of pleural spread [83]. In one series of 22 patients who underwent thymectomy for stage I thymoma, a patient (who may have been incorrectly assigned stage I disease) was reoperated on 3 years later for pulmonary thymoma metastases and was found to have recurrence along the pleural aspect of the utility thoracotomy scar [79].

Deeb and colleagues [84] have published articles on the role of transcervical thymectomy, which was studied in a select group of patients with suspected thymoma. Results in stage I and II were promising, but the authors did extend their incision to a sternotomy in 36% of the pathologic-proven thymomas.

Icard and colleagues [85] have recently demonstrated the technical feasibility of using a mini-sternotomy for complete excision of stage I and II thymomas. All patients had complete resection and the three stage II thymomas received adjuvant treatment. No data regarding regional recurrence or survival were provided.

Ohta and colleagues [86] have described resection of two stage I thymomas using an endoscopic approach in which the view of the mediastinum is maximized by elevating the thoracic wall using bilateral rib hooks. The authors claim that this approach has the advantage that dissection begins along the deep surface of the thymus and as a consequence early recognition of unexpected pericardial or great vessel involvement is facilitated. According to the authors, any such involvement would precipitate conversion to sternotomy. A different endoscopic approach to extended thymectomy for thymoma has also been described using elevation of the sternum itself [87]. At the time of writing of this article, there exists insufficient data in the literature to make comments regarding the appropriateness of approaches to thymectomy in thymoma other than sternotomy, because objective assessments of outcome are lacking.

Although we have treated the topics addressed so far (ie, the extent of resection, adequacy of surgery alone, de-bulking, re-resection and minimally invasive thymectomy) as stand-alone questions, they are best evaluated within each of the thymoma stages. Table 7 lists the stage-specific treatment recommendations on the role of surgery in thymoma.


View this table:
[in this window]
[in a new window]

  		Table 7 Evidence-Based Treatment Recommendations
 
The evidence on which we based our recommendations is level V evidence (ie, retrospective uncontrolled case series). The sole exception is a small randomized, controlled trial of adjuvant radiotherapy in stage I thymomas. Nonetheless, this systematic review suggests that whenever possible, a complete resection of thymoma affords maximal survival advantage.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies Int J Cancer 2003;105:546-551.[Medline]
  2. Gray GF, Gutowski. Thymoma. A clinicopathologic study of 54 cases. WT3 Am J Surg Pathol 1979;3:235-249.[Medline]
  3. 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.[Abstract/Free Full Text]
  4. 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.[Abstract/Free Full Text]
  5. Awad WI, Symmans PJ, Dussek JE. Recurrence of stage I thymoma 32 years after total excision Ann Thorac Surg 1998;66:2106-2108.[Abstract/Free Full Text]
  6. Levine GD, Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts Hum Pathol 1978;9:495-515.[Medline]
  7. Zhang Z, Ren H, Yu H, et al. Thymic carcinoid tumor–a report of 7 cases Chin Med Sci J 1993;8:48-51.[Medline]
  8. Asbun HJ, Calabria RP, Calmes S, et al. Thymic carcinoid Am Surg 1991;57:442-445.[Medline]
  9. Economopoulos GC, Lewis Jr JW, Lee MW, et al. Carcinoid tumors of the thymus Ann Thorac Surg 1990;50:58-61.[Abstract]
  10. Rosai JLG. Tumors of the thymusWashington, DC: Armed Forces Institue of Pathology; 1976.
  11. Maggi G, Casadio C, Cavallo A, et al. Thymoma: results of 241 operated cases Ann Thorac Surg 1991;51:152-156.[Abstract]
  12. Kondo K, Yoshizawa K, Tsuyuguchi M, et al. WHO histologic classification is a prognostic indicator in thymoma Ann Thorac Surg 2004;77:1183-1188.[Abstract/Free Full Text]
  13. Nakagawa K, Asamura H, Matsuno Y, et al. Thymoma: a clinicopathologic study based on the new World Health Organization classification J Thorac Cardiovasc Surg 2003;126:1134-1140.[Abstract/Free Full Text]
  14. Rios A, Torres J, Galindo PJ, et al. Prognostic factors in thymic epithelial neoplasms Eur J Cardiothorac Surg 2002;21:307-313.[Abstract/Free Full Text]
  15. Lardinois D, Rechsteiner R, Lang RH, et al. Prognostic relevance of Masaoka and Muller-Hermelink classification in patients with thymic tumors Ann Thorac Surg 2000;69:1550-1555.[Abstract/Free Full Text]
  16. Sassa K, Mizushima Y, Kusajima Y, et al. Clinical study on thymoma: assessment of prognostic factors Anticancer Res 1996;16:3895-3900.[Medline]
  17. Latz D, Schraube P, Oppitz U, et al. Invasive thymoma: treatment with postoperative radiation therapy Radiology 1997;204:859-864.[Abstract/Free Full Text]
  18. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan Ann Thorac Surg 2003;76:878-884.[Abstract/Free Full Text]
  19. Mayer R, Beham-Schmid C, Groell R, et al. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review. Strahlenther Onkol 1999;175:271-278.[Medline]
  20. 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.[Medline]
  21. Moore KH, McKenzie PR, Kennedy CW, et al. Thymoma: trends over time Ann Thorac Surg 2001;72:203-207.[Abstract/Free Full Text]
  22. Gawrychowski J, Rokicki M, Gabriel A, et al. Thymoma—the usefulness of some prognostic factors for diagnosis and surgical treatment Eur J Surg Oncol 2000;26:203-208.[Medline]
  23. Haniuda M, Morimoto M, Nishimura H, et al. Adjuvant radiotherapy after complete resection of thymoma Ann Thorac Surg 1992;54:311-315.[Abstract]
  24. Wilkins Jr EW, Grillo HC, Scannell JG, et al. J. Maxwell Chamberlain memorial paper. Role of staging in prognosis and management of thymoma. Ann Thorac Surg 1991;51:888-892.[Abstract]
  25. Okumura M, Miyoshi S, Takeuchi Y, et al. Results of surgical treatment of thymomas with special reference to the involved organs J Thorac Cardiovasc Surg 1999;117:605-613.[Abstract/Free Full Text]
  26. Nakahara K, Ohno K, Hashimoto J, et al. Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients J Thorac Cardiovasc Surg 1988;95:1041-1047.[Abstract]
  27. Matsushima S, Yamamoto H, Egami K, et al. Evaluation of the prognostic factors after thymoma resection Int Surg 2001;86:103-106.[Medline]
  28. Sasaki H, Yukiue H, Kobayashi Y, et al. Cten mRNA expression is correlated with tumor progression in thymoma Tumour Biol 2003;24:271-274.[Medline]
  29. Sasaki H, Kobayashi Y, Yukiue H, et al. Hrad17 expression in thymoma Jpn J Thorac Cardiovasc Surg 2003;51:81-85.[Medline]
  30. Sasaki H, Dai M, Auclair D, et al. Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients Cancer Lett 2001;172:37-42.[Medline]
  31. Sperling B, Marschall J, Kennedy R, et al. Thymoma: a review of the clinical and pathological findings in 65 cases Can J Surg 2003;46:37-42.[Medline]
  32. Wilkins KB, Sheikh E, Green R, et al. Clinical and pathologic predictors of survival in patients with thymoma Ann Surg 1999;230:562-572.[Medline]
  33. Blumberg D, Port JL, Weksler B, et al. Thymoma: a multivariate analysis of factors predicting survival Ann Thorac Surg 1995;60:908-913.[Abstract/Free Full Text]
  34. Wang LS, Huang MH, Lin TS, et al. Malignant thymoma Cancer 1992;70:443-450.[Medline]
  35. Froudarakis ME, Tiffet O, Fournel P, et al. Invasive thymoma: a clinical study of 23 cases Respiration 2001;68:376-381.[Medline]
  36. Fujimura S, Kondo T, Handa M, et al. Results of surgical treatment for thymoma based on 66 patients J Thorac Cardiovasc Surg 1987;93:708-714.[Abstract]
  37. Muller-Hermelink HK, Marx A. Thymoma Curr Opin Oncol 2000;12:426-433.[Medline]
  38. Tsuchiya M, Asakura H, Yoshimatsu H. Thymic abnormalities and autoimmune diseases Keio J Med 1989;38:383-402.[Medline]
  39. Evoli A, Minisci C, Di Schino C, et al. Thymoma in patients with MG: characteristics and long-term outcome Neurology 2002;59:1844-1850.[Abstract/Free Full Text]
  40. De Assis JL, Zambon AA, Souza PS, et al. Myasthenia gravis and thymoma. Evaluation of 41 patients. Arq Neuropsiquiatr 1999;57:6-13.[Medline]
  41. Goldman AJ, Herrmann Jr C, Keesey JC, et al. Myasthenia gravis and invasive thymoma: a 20-year experience Neurology 1975;25:1021-1025.[Abstract/Free Full Text]
  42. Papatestas AE, Pozner J, Genkins G, et al. Prognosis in occult thymomas in myasthenia gravis following transcervical thymectomy Arch Surg 1987;122:1352-1356.[Abstract/Free Full Text]
  43. Akoum R, Brihi E, Chammas S, et al. Results of radiation therapy for thymoma based on a review of 27 patients Mol Immunol 2003;39:1115-1119.[Medline]
  44. Lequaglie C, Giudice G, Brega Massone PP, et al. Clinical and pathologic predictors of survival in patients with thymic tumors J Cardiovasc Surg (Torino) 2002;43:269-274.[Medline]
  45. Sugiura H, Morikawa T, Ito K, et al. Long-term results of surgical treatment for invasive thymoma Anticancer Res 1999;19:1433-1437.[Medline]
  46. Venuta F, Rendina EA, Longo F, et al. Long-term outcome after multimodality treatment for stage III thymic tumors Ann Thorac Surg 2003;76:1866-1872.[Abstract/Free Full Text]
  47. Etienne T, Deleaval PJ, Spiliopoulos A, et al. Thymoma: prognostic factors Eur J Cardiothorac Surg 1993;7:449-452.[Abstract]
  48. Baraka A. Anesthesia and critical care of thymectomy for myasthenia gravis Chest Surg Clin N Am 2001;11:337-361.[Medline]
  49. Hejna M, Haberl I, Raderer M. Nonsurgical management of malignant thymoma Cancer 1999;85:1871-1884.[Medline]
  50. Detterbeck FC. Clinical value of the WHO classification system of thymoma Ann Thorac Surg 2006;81:2328-2334.[Abstract/Free Full Text]
  51. Wright CD, Kessler KA. Surgical treatment of thymic tumors Semin Thorac Cardiovasc Surg 2005;17:20-26.[Medline]
  52. Kesler KA, Wright CD, Loehrer Sr PJ. Thymoma: current medical and surgical management Semin Neurol 2004;24:63-73.[Medline]
  53. Limet R, Rogister B. Surgery of the thymus gland, normal, atrophied or cancerous Rev Med Liege 2000;55:940-944.[Medline]
  54. Shamji F, Pearson FG, Todd TR, et al. Results of surgical treatment for thymoma J Thorac Cardiovasc Surg 1984;87:43-47.[Abstract]
  55. Murakawa T, Nakajima J, Kohno T, et al. Results from surgical treatment for thymoma. 43 years of experience. Jpn J Thorac Cardiovasc Surg 2000;48:89-95.[Medline]
  56. Mehran R, Ghosh R, Maziak D, et al. Surgical treatment of thymoma Can J Surg 2002;45:25-30.[Medline]
  57. Schmidt R, Monig SP, Selzner M, et al. Surgical therapy of malignant thymoma J Cardiovasc Surg (Torino) 1997;38:317-322.[Medline]
  58. Port JL, Ginsberg RJ. Surgery for thymoma Chest Surg Clin N Am 2001;11:421-437.[Medline]
  59. Langenfeld J, Graeber GM. Current management of thymoma Surg Oncol Clin N Am 1999;8:327-339.[Medline]
  60. Maggi G, Giaccone G, Donadio M, et al. Thymomas: a review of 169 cases, with particular reference to results of surgical treatment Cancer 1986;58:765-776.[Medline]
  61. Braitman H, Li W, Herrmann Jr C, et al. Surgery for thymic tumors Arch Surg 1971;103:14-16.[Abstract/Free Full Text]
  62. Yoneda S, Matsuzoe D, Kawahara K, et al. Surgical therapy for patients with thymoma or thymic carcinoma; based on WHO classification Kyobu Geka 2002;55:926-930.[Medline]
  63. Sugiura H, Morikawa T, Ito K, et al. Long-term results of surgical treatment for invasive thymoma Anticancer Res 1999;19:1433-1437.[Medline]
  64. Shimizu N, Moriyama S, Aoe M, et al. The surgical treatment of invasive thymoma. Resection with vascular reconstruction. J Thorac Cardiovasc Surg 1992;103:414-420.[Abstract]
  65. Schutzner J, Smat V, Pafko P, et al. Surgical therapy of thymomas Sb Lek 1999;100:27-31.[Medline]
  66. Guyatt GH, Cook DJ, Sackett DL, et al. Grades of recommendation for antithrombotic agents Chest 1998;114:441S-444S.[Medline]
  67. Zhang H, Lu N, Wang M, et al. Postoperative radiotherapy for stage I thymoma: a prospective randomized trial in 29 cases Chin Med J (Engl) 1999;112:136-138.[Medline]
  68. Mehran R, Ghosh R, Maziak D, et al. Surgical treatment of thymoma Can J Surg 2002;45:25-30.[Medline]
  69. Gronseth GS, Barohn RJ. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2000;55:7-15.[Free Full Text]
  70. Yagi K, Hirata T, Fukuse T, et al. Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded Ann Thorac Surg 1996;61:521-524.[Abstract/Free Full Text]
  71. Singhal S, Shrager JB, Rosenthal DI, et al. Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation Ann Thorac Surg 2003;76:1635-1641.[Abstract/Free Full Text]
  72. Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy for stage II thymoma Ann Thorac Surg 2002;74:1033-1037.[Abstract/Free Full Text]
  73. Mangi AA, Wain JC, Donahue DM, et al. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg 2005;79:1834-1839.[Abstract/Free Full Text]
  74. Liu HC, Chen YJ, Tzen CY, et al. Debulking surgery for advanced thymoma Eur J Surg Oncol 2006;32:1000-1005.[Medline]
  75. Regnard JF, Zinzindohoue F, Magdeleinat P, et al. Results of re-resection for recurrent thymomas Ann Thorac Surg 1997;64:1593-1598.[Abstract/Free Full Text]
  76. Haniuda M, Kondo R, Numanami H, et al. Recurrence of thymoma: clinicopathological features, re-operation, and outcome J Surg Oncol 2001;78:183-188.[Medline]
  77. Landreneau RJ, Dowling RD, Castillo WM, et al. Thoracoscopic resection of an anterior mediastinal tumor Ann Thorac Surg 1992;54:142-144.[Abstract]
  78. Yim AP. Video-assisted thoracoscopic resection of anterior mediastinal masses Int Surg 1996;81:350-353.[Medline]
  79. Roviaro G, Varoli F, Nucca O, et al. Videothoracoscopic approach to primary mediastinal pathology Chest 2000;117:1179-1183.[Medline]
  80. Ruckert JC, Gellert K, Muller JM. Operative technique for thoracoscopic thymectomy Surg Endosc 1999;13:943-946.[Medline]
  81. Cheng YJ, Wu HH, Chou SH, et al. Video-assisted thoracoscopic management of mediastinal tumors JSLS 2001;5:241-244.[Medline]
  82. Yoshino I, Hashizume M, Shimada M, et al. Thoracoscopic thymomectomy with the da Vinci computer-enhanced surgical system J Thorac Cardiovasc Surg 2001;122:783-785.[Free Full Text]
  83. Yellin A. Video-assisted thoracoscopic surgery. Thymectomy. Chest 1996;110:578-579.[Medline]
  84. Deeb ME, Brinster CJ, Kucharzuk J, et al. Expanded indications for transcervical thymectomy in the management of anterior mediastinal masses Ann Thorac Surg 2001;72:208-211.[Abstract/Free Full Text]
  85. Icard P, Le Page O, Massetti M, et al. Resection of anterior mediastinal tumor through a ministernotomy: preliminary experience with ten cases J Thorac Cardiovasc Surg 2003;125:432-434.[Free Full Text]
  86. Ohta M, Hirabayasi H, Okumura M, et al. Thoracoscopic thymectomy using anterior chest wall lifting method Ann Thorac Surg 2003;76:1310-1311.[Abstract/Free Full Text]
  87. Takeo S, Sakada T, Yano T. Video-assisted extended thymectomy in patients with thymoma by lifting the sternum Ann Thorac Surg 2001;71:1721-1723.[Abstract/Free Full Text]
  88. Sonobe M, Nakagawa M, Ichinose M, et al. Thymoma. Analysis of prognostic factors. Jpn J Thorac Cardiovasc Surg 2001;49:35-41.[Medline]
  89. Whooley BP, Urschel JD, Antkowiak JG, et al. A 25-year thymoma treatment review J Exp Clin Cancer Res 2000;19:3-5.[Medline]
  90. Murakawa T, Nakajima J, Kohno T, et al. Results from surgical treatment for thymoma: 43 years of experience Jpn J Thorac Cardiovasc Surg 2000;48:89-95.[Medline]
  91. Gripp S, Hilgers K, Wurm R, et al. Thymoma: prognostic factors and treatment outcomes Cancer 1998;83:1495-1503.[Medline]
  92. McCart JA, Gaspar L, Inculet R, et al. Predictors of survival following surgical resection of thymoma J Surg Oncol 1993;54:233-238.[Medline]
  93. Mangi AA, Wain JC, Donahue DM, et al. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg 2005;79:1834-1839.[Abstract/Free Full Text]
  94. Liu HC, Chen YJ, Tzen CY, et al. Debulking surgery for advanced thymoma Eur J Surg Oncol 2006;32:1000-1005.[Medline]
  95. Okumura M, Shiono H, Inoue M, et al. Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system J Surg Oncol 2007;95:40-44.[Medline]
  96. Urgesi A, Monetti U, Rossi G, et al. Aggressive treatment of intrathoracic recurrences of thymoma Radiother Oncol 1992;24:221-225.[Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Richard A. Malthaner
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Davenport, E.
Right arrow Articles by Malthaner, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davenport, E.
Right arrow Articles by Malthaner, R. A.
Related Collections
Right arrow Mediastinum

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS