Resection Of Thymoma Research Articles

Oncological outcomes of thoracoscopic thymectomy for the treatment of stages I–III thymomas

Thoracoscopic thymectomy has gradually replaced conventional sternotomy for resection of thymoma; however, a thoracoscopic approach for thymoma remains controversial. We evaluated the oncological outcomes of thoracoscopic thymectomy for the treatment of stages I-III thymomas. Sixty-two patients who underwent thoracoscopic thymectomy for the treatment of thymoma were retrospectively reviewed between July 2005 and September 2011 at Jikei University Hospital. Surgical outcomes and pathological results between stages I+II and stage III were compared. Twenty-nine patients had Masaoka stage I, 28 had stage II and 5 had stage III. Three stage III patients needed conversions to open surgery. Masaoka stage III comprised pathological type B3 in 3 patients and thymic carcinoma in 2. For all patients, the 5-year overall survival rate was 100%. Three recurrences, diagnosed as thymic carcinoma, were observed in the Masaoka stage II or III patients. The 5-year disease-free survival rate was 94.2% for all patients, 100% for Masaoka stage I, 96.1% for stage II and 37.5% (55 months) for stage III (P=0.002). The 5-year disease-free survival rate was 100% for the World Health Organization classification types A, AB and B1-3 and 0% for thymic carcinoma (P<0.0001). Significant differences were found in the 5-year disease-free survival stratified by the Masaoka stage or WHO classification, but not by surgical procedures. Thoracoscopic thymectomy for Masaoka stages I and II thymomas presented acceptable oncological outcomes. Further investigation in a large series with longer follow-up is required. Masaoka stage III thymoma requires careful consideration of the approaches, including median sternotomy.

Myocarditis after thymoma resection, with left ventricular hypokinesia mimicking acute coronary syndrome

Myocarditis after thymoma resection, with left ventricular hypokinesia mimicking acute coronary syndrome

Thoracic Techniques: Robotic Thymectomy for Thymoma

The traditional approach to resection of anterior mediastinal masses has been via sternotomy. This approach has been associated with an average length of stay of 4–5 days, sternal precautions for 6 weeks, a visible scar, and in some cases, long term discomfort. Although some surgeons have attempted VATS resection of thymomas and other anterior mediastinal masses, we have found that a robotic assisted resection, with its enhanced vision (due to the 10× magnification) and endowrist movements, are ideal for the compact space of the anterior mediastinum [1]. Herein, we describe our technique of total thymectomy for thymoma, highlight some adjunctive techniques, discuss the results of robotic thymectomy, and identify the controversies around robotic resection for thymoma.

Predictors of Recurrence after Thymoma Resection

PurposeRecurrence rate is considered a better measure of clinical outcomes after thymoma resection than overall survival due to the indolent behavior of thymomas. This study was designed to determine predictors of recurrence after thymoma resection.Materials and MethodsA single-institution, retrospective study was performed, including 305 patients who had undergone thymoma resection between 1986 and 2009.ResultsAmong 305 patients, recurrence was observed in 41 patients (13.4%). The recurrence rates were 0% (0/19), 6.3% (4/63), 4.2% (2/48), 18.6% (11/59) and 20.7% (24/116) for type A, AB, B1, B2 and B3 tumors, respectively. The recurrence rate according to Masaoka stage was 6.1% (8/132), 11.4% (13/114), 26.8% (11/41) and 50.0% (9/18) for stages I, II, III and IV, respectively. After univariate analysis, completeness of resection (R0 versus R1), World Health Organization (WHO) histologic type (A, AB, B1 versus B2, B3), Masaoka stage, and size of tumor (<8 cm versus ≥8 cm) demonstrated significant differences with freedom from recurrence. Upon multivariate analysis, Masaoka stage was the only independent predictor of recurrence.ConclusionWHO histologic type, Masaoka stage, and size of tumor were associated with recurrence. Particularly, Masaoka stage was the only independent predictor of recurrence after thymoma resection.

A Case of Spontaneous Remission Organizing Pneumonia after Resection of Thymoma

Thymoma is a rare neoplasm associated with a number of autoimmune disorders and tumors. Organizing pneumonia is a reaction of the lung to various injuries. A feature of organizing pneumonia is plugs of granulation tissue within the lumens of small airways, or alveoli. Causes of organizing pneumonia include various disorders and conditions; however, thymoma with organizing pneumonia located in both lungs is very rare. We report a case of resolving organizing pneumonia after thymoma resection. Our case is the first to demonstrate that resolving organizing pneumonia can occur after thymoma resection, as has been speculated by many researchers. (Korean J Med 2013;85:92-95) Keywords: Organizing pneumonia; Thymoma 중심 단어: ê¸°ì§ˆí™”íë ´; í‰ì„ ì¢

Expression and Clinical Significance of Protein Tyrosine Phosphatase Nonreceptor 22 in Resected Thymoma

To investigate the expression and clinical significance of protein tyrosine phosphatase nonreceptor 22 (PTPN22) in thymoma, as well as the relationship between thymoma and myasthenia gravis (MG). The expression of PTPN22 in normal thymus (35 cases), thymoma without MG (50 cases), and thymoma with MG (45 cases) treated with surgery were detected by the EnVision two-step immunohistochemical staining method. We analyzed the relationship of thymoma with MG as well as some clinical factors, such as the Osserman classification for MC, age, gender, and course of disease before surgery. All data were analyzed using the SPSS software. The positive rates of PTPN22 expression in thymoma with and without MG were 11.1% (5/45) and 24.0% (12/50), respectively, which were significantly lower than in the normal thymus (74.3%, 26/35). A significant difference was found between the positive rates of thymoma with and without MG. The expression level of PTPN22 had no relation to thymoma with MG and to the Osserman classification for MG, age, gender, and course of disease of the patient. Minimal or no PTPN22 expression in thymoma may play an important role in the development of thymoma with MG, provide basis for further genetic research.

Anterior Mediastinal Lymphoma Arising after Resection of an Invasive Thymoma and Immunosuppressive Therapy for Complicated Myasthenia Gravis

We present the case of a 56-year-old woman with an anterior mediastinal tumor who has past history of myasthenia gravis and invasive thymoma. Furthermore, she had superior vena cava syndrome that was caused by a rapidly growing tumor. A biopsy proved diffuse large B-cell lymphoma. After 8 courses of chemotherapy, remission of the lymphoma was achieved. Because a second primary malignancy, including lymphoma, can occur in patients with thymoma, a biopsy is necessary for tumors located in the anterior mediastinum, particularly in patients with a history of treatment for thymoma, to distinguish between recurrence and a second primary malignancy.

Reproducibility of the WHO classification of thymomas: Practical implications

BackgroundThe WHO-classification was shown to be an independent prognostic marker in some but not all retrospective studies possibly due to lack of reproducibility. We investigated the reproducibility of the WHO-classification and its prognostic implication using a large series of resected thymomas. MethodsFour independent pathologists histologically classified a surgical series of 129 thymic tumors in a blinded fashion. Fleiss’ kappa-coefficient was used to assess the pathologists’ overall agreement, and Cohen-Kappa to assess the agreement between two observers. Disease-related-survival (DRS) and progression-free-survival (PFS) curves were generated by Kaplan–Meier method and compared by log-rank test. ResultsIn 63/129 (48.8%) cases there was a complete agreement; in 43/129 (33.3%) cases 3/4 pathological diagnoses were identical; in 15/129 (11.6%) cases the diagnoses were identical by pair; in 8/129 (6.2%) cases three different pathological diagnoses were on record. The Kappa-correlation coefficient was only moderate (0.53). A following web review carried out on the 23 cases with at least two different diagnoses reached a complete consensus. The histotype showed a statistically significant impact on PFS and DRS in the classification provided by only two pathologists. ConclusionsIn this study, the agreement on WHO classification of thymomas was only moderate and this impacted on patients management. Web consensus conference on the diagnosis, more stringent diagnostic criteria or the adoption of referral diagnostic centres may substantially reduce discrepancies.

It is feasible to operate on pathological Masaoka stage I and II thymoma patients with video-assisted thoracoscopy: analysis of factors for a successful resection

The objectives of this study were to evaluate the feasibility of video-assisted thoracoscopic (VATS) thymoma resection and to analyze the factors contributing to a successful perioperative period. Fifty-one patients with thymoma underwent VATS with the aim of thymoma resection. Four patients underwent minithoracotomy [due to technical difficulties, including small chest cavity, high body mass index (BMI), and disintegration of the capsule] and three patients underwent sternotomy (due to invasion of major vascular structures). The seven open-converted patients and seven other patients who underwent complete VATS thymoma resection but experienced prolonged hospital stay (≥7 days) formed Group B (n = 14), namely, the unsuccessful group, while successful VATS thymoma resection patients formed Group A (n = 37). The groups were compared with each other in terms of the characteristics of patients, tumors, and perioperative period. Patients' characteristics, tumor size, WHO histologic type, and complications were similar in both Groups A and B (p > 0.05). Patients with Masaoka stage I and II thymomas were significantly more frequent in Group A (p < 0.01). Tumor size was a statistically insignificant variable for the determination of a successful VATS thymoma resection (p = 0.3). Masaoka stage and the size of the thymoma did not have any correlation with each other (p > 0.05). The size of the thymoma was not observed to be correlated with Masaoka stage and it was not noted to be an important factor in successful VATS thymoma resection. A higher Masaoka stage (III and IVa) was found to be the only variable that predicted unsuccessful situations. Thus, Masaoka stage, rather than the size of the thymoma, should be the main concern for the surgeon.

PTPN22 and CTLA-4 gene polymorphisms in resected thymomas and thymus for myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease of striated muscle tissue mediated by autoantibodies. MG is often treated with thymectomy. Protein tyrosine phosphatase non-receptor 22 (PTPN22) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have recently been found to be the genes that predispose to autoimmune diseases. The mechanisms of PTPN22 and CTLA-4 single nucleotide polymorphisms in resected thymomas and thymuses in MG remain unclear. In the present study, 90 patients with thymomas, including 44 patients with MG, 46 patients without MG, and 35 MG patients without thymoma were studied, with 50 healthy people as the controls. The +1858C>T polymorphism of the PTPN22 gene and the 49A>G polymorphism of the CTLA-4 gene were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The PTPN22 -1123G>C polymorphism at the promoter site was genotyped using single allele-specific primer polymerase chain reaction (SASP-PCR). The PTPN22 +1858C>T polymorphism was not significantly different between the patients and the controls. Statistically significant differences in the allelic and genotypic frequencies of PTPN 22 -1123G>C and CTLA-4 49A>G were observed between the MG(+)-thymoma group and the controls (P = 0.000, 0.003), but not between the MG(-)-thymoma and MG-thymoma(-) groups and the controls (P = 0.192/P = 0.214 and P = 0.067/P = 0.254). Statistically significant differences in allelic and genotypic frequencies of the 49A>G for CTLA-4 were observed between the MG(+)-thymoma group and the controls (P = 0.000, P = 0.003), but not between the MG(-)-thymoma and MG-thymoma(-) groups and the controls (P = 0.077/P = 0.261 and P = 0.058/P = 0.058). Individuals with the PTPN22 CC genotype and the CTLA-4 G alleles had an increased risk of developing paraneoplastic MG (odds ration [OR]= 4.722, 95% confidence interval [CI]: 1.460-15.277) compared with those with the PTPN22 G allele and the CTLA-4 AA genotype. The results show an association between the PTPN22 1123G>C genotype and thymoma-associated MG, with significant synergy with the CTLA-4 G alleles.

Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging

Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma. This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006. A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease. Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.

Aortic pseudoaneurysm due to graft infection after invasive thymoma resection

A 69-year-old woman with invasive thymoma underwent chemoradiotherapy followed by surgical resection, including extended thymectomy, right upper lobectomy, and innominate vein and superior vena cava reconstruction with a polytetrafluoroethylene graft. Computed tomography on the 27th postoperative day revealed mediastinitis and right hemothorax; open debridement and evacuation were performed. Vacuum-assisted closure was initiated to heal the median incision. The wound gradually cleared, and the vacuum was terminated on the 150th postoperative day. On the 155th postoperative day, the patient suffered a sudden hemorrhage from the anterior thoracic wall. Computed tomography revealed a ruptured ascending aortic pseudoaneurysm surrounding the graft.

Clinical Outcomes and Prognosis of Recurrent Thymoma Management

Clinical outcomes and prognosis of recurrent thymoma are not well known because of its rarity and indolent clinical course. This study was designed to determine the clinical outcomes and prognosis of recurrent thymoma. Between 1986 and 2009, 41 of 305 patients who underwent resection for thymoma had recurrence. We reviewed those patients retrospectively. Of 15 patients who underwent re-resection for recurrent thymoma, 13 patients (87%) achieved complete re-resection. Of 26 patients who did not undergo re-resection, 11 patients received chemotherapy, five received chemoradiotherapy, one received another treatment, and nine patients did not receive any treatment. World Health Organization histological types AB or B1 and complete re-resection were positive prognostic factors. The complete re-resection group had better survival after recurrence than the non/incomplete re-resection group (5-year survival rate: 90.9% versus 44.7%, p = 0.014). The complete re-resection group had comparable survival after initial resection of thymoma to the patients without recurrence (5-year, 10-year survival: 91.7%, 91.7% versus 90.7%, 86.5%, p = 0.618) and better survival compared with the non/incomplete re-resection group (5-year, 10-year survival: 91.7%, 91.7% versus 81.6%, 56.7%, p = 0.018). World Health Organization histologic types AB or B1 and complete re-resection are favorable prognostic factors of recurrent thymoma. In particular, complete re-resection of recurrent thymoma contributes to better survival than other management. Therefore, we suggest that long-term surveillance extended at least 20 years may be essential for early detection of recurrence to increase the chance of complete re-resection of recurrent thymoma.

Minimally invasive resection of thymomas with the da Vinci(R) Surgical System

The resection of thymic tumours requires completeness and may be technically challenging due to the anatomical proximity of the delicate mediastinal structures. An open approach by sternotomy is still recommended in all cases with locally extended disease. Video-assisted thoracoscopic surgery is feasible, but limited by the two-dimensional vision and the impaired mobility of the instruments. We evaluated the da Vinci® Surgical System for the resection of various mediastinal pathologies, particularly thymomas. Among 105 patients operated on by robotic assisted thoracoscopic surgery (RATS) for mediastinal tumours between 27 August 2004 and 12 July 2011, 20 patients with thymomas were studied prospectively. Of these, 10 males with a median age of 53 years, with a well-circumscribed thymic lesion on computed tomography (CT) and a diameter of <6 cm were resected by RATS alone, and selected ones (n = 3), with a diameter of >6 cm, underwent a hybrid procedure with a contralateral thoracotomy on the side of the main tumour extension. A regular follow-up with chest CT scans was performed every 6 months. Thymoma resection was complete in all patients. Partial pericardial resection was needed in five and pulmonary resection in two patients. Eighty-five percent of patients had an R0 resection. Histological classifications included thymoma WHO type A (n = 3), AB (n = 8), B1-2 (n = 5) and B3 (n = 4). All B3 thymomas received adjuvant radiotherapy. No intraoperative complications occurred. The median hospitalization time was 5 days (range 2-14 days). There were no local, but two pleural, recurrences. After a median observation time of 26 months, 19 patients (95%) are alive. Well-circumscribed thymomas can be safely and completely resected with the da Vinci® Surgical System with excellent short- and mid-term outcomes. Selected tumours with large diameters may be resectable using a hybrid procedure combining RATS with a thoracotomy.

Minimally Invasive Thymectomy and Open Thymectomy: Outcome Analysis of 263 Patients

An open thymectomy is a morbid procedure. If a minimally invasive thymectomy is performed without compromising the tenets of thymic surgery, it has the potential for decreasing morbidity and may offer similar clinical and oncologic results. This is an institutional review board-approved, retrospective study of a single center's experience with both open (transsternal) and minimally invasive (video-assisted thoracoscopic surgery) thymectomy. Survival estimates and statistical comparisons were calculated using standard software. From 2000 to 2011, 263 patients (93 men; median age, 49 years; interquartile range, 37 to 60 years) underwent thymectomy for indications including myasthenia gravis (n=139) and mediastinal mass (n=108). Seventy-seven thymectomies were performed by minimally invasive approach. Both groups were equally stratified by sex, body mass index, World Health Organization and Masaoka-Koga staging, incidence of myasthenia gravis, and comorbidities except hyperlipidemia and diabetes. The minimally invasive thymectomy cohort had significantly shorter hospital (p<0.01) and intensive care unit lengths of stay (p<0.01) and a lower estimated blood loss (p<0.01). There was an insignificant difference in postoperative cardiac and respiratory complication rates as well as vocal cord paralysis (p=0.60). There was no difference in terms of operative room times (p=0.88) or volume of blood products transfused (p=0.16) between the two groups. Higher estimated blood loss was associated with higher intensive care unit admission rates (p<0.01). All minimally invasive thymoma resections were complete, with negative margins. Minimally invasive thymectomy is safe and achieves a comparable resection and postoperative complication profile when used selectively for all indications, including myasthenia gravis and small thymomas without vascular invasion.

Edema pulmonar por reexpansión tras resección de timoma gigante

A 36 year-old woman who was subjected to resection of a giant thymoma that occupied a large area of the left hemithorax. After resection of the tumour and insufflation of the left lung there was pulmonary oedema due to early re-expansion. She was treated with diuretics and corticoids and was kept on mechanical ventilation. The patient progressed favourably. Although pulmonary oedema due to re-expansion is an uncommon complication it has a high mortality. It is essential to be aware of the factors involved in its aetiopathogenesis. It should be diagnosed and treated immediately.

Myasthenia gravis appearing 18 years after resection of benign thymoma with subsequent limbic encephalitis

Thymoma is associated with multiple autoimmune disorders, most commonly myasthenia gravis (MG). However, symptomatic MG may first present following thymectomy. We report an unusual patient with paraneoplastic limbic encephalitis diagnosed a few months after total thymectomy for asymptomatic thymoma, followed 18years later by the onset of symptomatic MG without evidence of tumor recurrence.

Giardia infection: Protein-losing enteropathy in an adult with immunodeficiency

The case of a 52-year-old woman with a past history of thymoma resection who presented with chronic diarrhea and generalized edema is the focal point of this article. A diagnosis of Giardia lamblia infection was established, which was complicated by protein-losing enteropathy and severely low serum protein level in a patient with no urinary protein loss and normal liver function. After anti-helmintic treatment, there was recovery from hypoalbuminemia, though immunoglobulins persisted at low serum levels leading to the hypothesis of an immune system disorder. Good's syndrome is a rare cause of immunodeficiency characterized by the association of hypogammaglobulinemia and thymoma. This primary immune disorder may be complicated by severe infectious diarrhea secondary to disabled humoral and cellular immune response. This is the first description in the literature of an adult patient with an immunodeficiency syndrome who presented with protein-losing enteropathy secondary to giardiasis.

Adjuvant Radiotherapy (RT) for Thymoma: A Dosimetric Comparison of Photon and Proton Based Treatment Techniques

Retrospective evidence and consensus guidelines support the use of RT for selected patients with resected Thymoma and unfavorable pathologic features. However, mediastinal radiation may be associated with significant treatment related toxicity including: pericarditis, radiation pneumonitis, long-term pulmonary fibrosis, and esophageal stricture. Proton therapy may provide improved therapeutic index in this setting by reducing dose to adjacent organs at risk (OAR). Prior studies comparing proton and photon based thoracic RT have not included patients with Thymoma.

Standard Terms, Definitions, and Policies for Minimally Invasive Resection of Thymoma

Having a common language including well-defined terms and adherence to certain policies and procedures in the management of patients with thymic malignancies is necessary to facilitate progress. This is especially true for minimally invasive resections. Different technical approaches have been used,1,2 and a careful examination of results is needed to understand the impact of the minimally invasive approach itself, as opposed to other factors. For example, during an open approach, most surgeons perform a complete en bloc resection of the tumor and a complete thymectomy with removal of the upper cervical poles and the surrounding mediastinal fat3; whether this is done during minimally invasive resections is hard to decipher at present. This article identifies key aspects that should be reported, common definitions that should be adopted and proposes certain standard policies that should be adhered to when performing a minimally invasive resection of a thymic malignancy. These definitions and policies do not apply to biopsies. These policies are not meant to stifle innovation; on the contrary, they should facilitate progress by providing a framework, so that experiences and outcomes can be compared and analyzed more clearly. These standards have been adopted by members of the International Thymic Malignancy Interest Group (ITMIG), which is a worldwide collaborative organization of individuals interested in mediastinal tumors. METHODS An initial work group of surgeons experienced in minimally invasive thymic resections was assembled to review definitions, terms, and procedures in the existing literature for minimally invasive thymoma resections (Alper Toker, Joshua Sonett, Marcin Zielinski, Federico Rea, Victor Tomulescu, and Frank C. Detterbeck). This work group formulated preliminary recommendations, which were refined by an extended work group (Harmik Soukiasian, Jens Ruckert, Mahmoud Ismail, Jeffrey Port, and Paul Van Schil). These were then debated among a large diverse group of specialists at an ITMIG workshop, which was supported by the International Association for the Study of Lung Cancer. After further comments by the entire ITMIG membership, the definitions and policies presented in this article were approved and adopted as a standard to follow in reporting data and discussing outcomes by the members of ITMIG.