Resection Of Thymoma Research Articles

Fatal giant cell myocarditis after thymoma resection in myasthenia gravis

2006;131:494-495 J Thorac Cardiovasc Surg Erwan M. Flecher and Phillippe G. Dartevelle Thomas M. Joudinaud, Elie Fadel, Vincent Thomas-de-Montpreville, Sacha Mussot, Fatal giant cell myocarditis after thymoma resection in myasthenia gravis http://jtcs.ctsnetjournals.org/cgi/content/full/131/2/494 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Myasthenia gravis developed 30 months after resection of recurrent thymoma

We have read the article by Kondo and Monden [1] with great interest. In our institution, post-thymectomy myasthenia gravis (MG) occurred in 2 of 91 patients (2%) with thymic epithelial tumors, previously diagnosed without MG (from June 1988 to June 2004). The incidence is similar to the findings of Namba et al. [2] and Ito et al. [3]. Previously, we reported a patient with thymic carcinoid who developed MG 31 days after thymomectomy [4]. Now, this patient who has been followed for 40 months has been in a state of complete remission from MG for 12 months. In this letter, we would like to share a rare experience about a patient who developed MG 30 months after resection of recurrent thymoma. A 43-year-old man with an incidental finding of a mediastinal tumor on his chest X-ray underwent complete thymomectomy because of stage IIb (Masaoka stage) thymoma (WHO type B1) on November 25, 1980. Although postoperative mediastinal radiation treatment (4500 cGy) was given, the tumor recurred in the right pleural cavity, necessitating a pleurectomy, partial diaphragmatic resection and right lower lobe lobectomy 35 months later. After the second operation, he received adjuvant chemoradiation therapy, including six applications of cisplatin-based chemotherapy and radiotherapy of the right chest cavity (total dose of 5040 cGy). Thirty months after the second operation, he developed a general type of MG and was placed under pyridostigmine and steroid therapy. Although no recurrence of thymoma in this patient was found, he eventually died from pulmonary tuberculosis in February 1990. At that time he still required a full dose of pyridostigmine and steroids to control the MG. The interval between thymomectomy and the onset of postoperative MG varies. Ito et al. [3] divided postthymectomy MG into earlyand late-onset types. Namba et al. [2] reported that patients with a shorter onset of postoperative MG had a better prognosis, but both Kondo’s and Ito’s studies did not find this tendency. Our results, although limited, support Namba’s findings. Ito et al. [3] ever reported five patients who had a delayed type of postoperative MG confirmed on thymoma recurrence. As mentioned in this letter, our patient showed that, after resection of recurrent thymoma, there is still a chance of developing late-onset type of postoperative MG. References

Invited commentary

The idea of clinical staging of thymoma was introduced by Bergh and colleagues [1Bergh N.P. Gatzinsky P. Larsson S. Lundin P. Ridell B. Tumors of the thymus and thymic region: I. Clinicopathological studies on thymomas.Ann Thorac Surg. 1978; 25: 91-98Abstract Full Text PDF PubMed Scopus (166) Google Scholar], which was later modified by Wilkins and Castleman [2Wilkins Jr, E.W. Castleman B. Thymoma a continuing survey at the Massachusetts General Hospital.Ann Thorac Surg. 1979; 28: 252-256Abstract Full Text PDF PubMed Scopus (114) Google Scholar], and was advanced by Masaoka and associates [3Masaoka A. Monden Y. Nakahara K. Tanioka T. Follow-up study of thymomas with special reference to their clinical stages.Cancer. 1981; 48: 2485-2492Crossref PubMed Scopus (1345) Google Scholar] in 1981. Masaoka’s system has been widely adopted and is an excellent system for predicting prognosis for thymomas. Several articles including the article by Bedini and associates [4Bedini A.V. Andreani S.M. Tavecchio L. et al.Proposal of a novel system for the staging of thymic epithelial tumors.Ann Thorac Surg. 2005; 80: 1994-2001Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar] have pointed out problems and have suggested that an update of the system is desirable. The authors identified seven major criticisms of the Masaoka system. I think that some criticisms are important (1 through 4), and I would like to add two additional staging issues (5 and 6): 1The classification system does not provide appreciable prognostic separation between stages I and II.2Some definitions are not clinically applicable because surgical or pathological assessment is required. In particular, the definition of stage II is unclear. Some pathologists propose that microscopic invasion into the capsule in stage II should be replaced by microscopic transcapsular invasion. The most recent World Health Organization classification of thymic epithelial tumors in 2004 defined T2 thymoma as “tumor invades pericapsular connective tissue” [5Müller-Hermelink H.K. Ströbel P. Zettl A. et al.Combined thymic epithelial tumours.in: Travis W.D. Brambilla E. Müller-Hermelink H.K. Harris C.C. Pathology and genetics of tumours of the lung, pleura, thymus and heart (WHO classification of tumours series). IARC Press, Lyon, France2004: 196-198Google Scholar].3The system is not well suited for staging thymic carcinomas.4Presence residual tumor is classified by use of the “R” category. Many reports demonstrate completeness of thymoma resection is the most important predictor of survival, although some reports show a value of so-called debulking procedures.5As stage III thymoma is highly heterogenous in terms of involved organs, classification should divide the subgroups according to prognosis. Okumura and associates [6Okumura 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: 605-613Abstract Full Text Full Text PDF PubMed Google Scholar] report that involvement of the great vessels is an independent prognostic factor in patients with stage III thymoma.6The TNM system classification of thymic epithelial tumors has not been established. Yamakawa and Masaoka [7Yamakawa Y. Masaoka A. Hashimoto T. et al.A tentative tumor-node-metastasis classification of thymoma.Cancer. 1991; 68: 1984-1987Crossref PubMed Scopus (147) Google Scholar] presented a tentative TNM system classification of thymoma in 1991, which some reports subsequently supported. In Masaoka’s system, the presence of local invasion (T factor) is strongly emphasized in comparison with lymphogenous and hematogenous metastasis (N and M factors) because of the rarity of lymphogenous and hematogenous metastasis in thymoma. However, it is necessary to determine how N or M factors influence prognosis to establish a TNM system classification of thymic epithelial tumors including thymic cancer and carcinoid. The World Health Organization’s histologic classification of 1999, which can distinguish thymic carcinoma and carcinoid from thymoma, has been widely adopted, and large-scale clinicopathologic studies of thymic carcinoma and carcinoid may provide sufficient prognostic information to include N or M factors in a TNM system of thymic epithelial tumor.

Long‐term disease‐free survival of patients with radically resected thymomas

Despite radical surgical resection, thymomas often recur. The objective of the current retrospective study was to investigate the prognostic relevance of the expression of cell-cycle proteins in these neoplasms to formulate a possible therapeutic surveillance strategy for the prevention of recurrence. The authors retrospectively reviewed the main clinicopathologic factors, including the World Health Organization (WHO) classification, of patients with thymoma who had undergone radical surgical resection. Specimens were studied using immunohistochemistry and the expression of cell-cycle proteins (i.e., p21, p27, and p53) was assessed. Univariate and multivariate analysis of predicting survival prognostic factors were performed. The authors analyzed 88 patients with thymoma who underwent radical surgical resection at the study institution. According to the Masaoka staging system, 41 patients had Stage I disease, 31 patients had Stage II disease, and 16 patients had Stage III disease. There were 24 tumor recurrences (27.3%), 4 of which were local, 16 of which were distant intrathoracic, and 4 of which were extrathoracic. The second radical resection provided a disease-free survival rate that was similar to the first. Only Masaoka stage (P = 0.001), WHO classification (P=0.001), high expression of p53 (P=0.03), and low expression of p21 (P=0.02) and p27 (P=0.001) were found to be correlated with a reduced disease-free survival. Low p27 expression was found to be the most significant predictive factor of a short disease-free survival (P=0.001), especially when associated with low p21 expression and high p53 expression (P=0.0001). Long-term disease-free survival in thymoma patients treated with radical surgical resection was found to be correlated with Masaoka stage, WHO classification, and expression of cell-cycle proteins, with the latter found to be the most significant predictive factor. Functional cooperation between cell-cycle proteins might constitute another level of regulation in tumor growth. More careful surveillance should be adopted whenever there is negative cell-cycle protein expression.

Videothoracoscopic Resection of Stage II Thymoma: Prospective Comparison of the Results Between Thoracoscopy and Open Methods

Although videothoracoscopic (VTS) resection of Masaoka stage I thymoma has been reported to be a less invasive method than open thoracotomy and to achieve a comparable surgical outcome, the usefulness of this method in the treatment of stage II thymoma has not yet been prospectively evaluated. We therefore compared the VTS and open (median sternotomy) methods to see whether VTS resection could be used as successfully to treat stage II thymoma disease.Patients (11 women and 11 men) with stage II thymoma were prospectively enrolled between November 1999 and September 2004. Of these, 12 patients (the VTS group) underwent tumor resection using a three-port endoscopic technique, and 10 patients (the open group) underwent tumor excision using a standard sternotomy approach. The diagnosis of all resected thymoma lesions and their stage were confirmed by histopathogic examination.Neither group experienced mortality or any major morbidity. The difference in mean age (+/- SD) between the VTS and open groups (40.2 +/- 16.3 years and 47.7 +/- 8.5 years, p = 0.202); mean operation time (193.3 +/- 79.6 min and 207.5 +/- 85.8 min, p = 0.692); mean duration of pleural drainage (4.2 +/- 2.1 days and 4.6 +/- 2.1 days, p = 0.702); and mean duration of postoperative hospital stay (6.8 +/- 2.3 days and 8.9 +/- 4.4 days, respectively; p = 0.157) were not statistically significant. However, mean intraoperative blood loss amounts were statistically different (119.2 +/- 70.6 mL and 238.5 +/- 110.2 mL, respectively; p = 0.006). During the mean follow-up period of 33.9 +/- 19.7 months, all patients survived without sign of recurrence, and the mean survival time was not statistically significant (32.3 +/- 22.0 months and 35.8 +/- 17.5 months, respectively; p = 0.686).Using careful and skillful technique, the VTS method is an effective treatment of stage II thymoma.

Mediastinitis and pseudoaneurysm of brachiocephalic artery long after the resection of invasive thymoma and postoperative irradiation

Mediastinitis is a complication after median sternotomy. We report a rare case of mediastinitis and mycotic pseudoaneurysm of the brachiocephalic artery that occurred long after the resection of invasive thymoma and postoperative irradiation and was treated with extensive procedures. Clinical Summary A 68-year-old woman was seen with skin ulceration and suppuration from the wound in the anterior chest wall. She had undergone resection of invasive thymoma through median sternotomy 65 months previously. This operative treatment included combined resection of pericardium, right lung, and superior vena cava, along with interposition of an artificial polytetrafluoroethylene graft between the brachiocephalic vein and the right atrium. The patient received adjuvant radiation therapy of 50 Gy to the mediastinum for pathologically diagnosed Masaoka stage III thymoma. Computed tomography of the chest showed a dilated branch of the aortic arch compressing the sternum posteriorly, an occluded artificial graft between the brachiocephalic vein and the right atrium, an dlow-densit yarea si nth emediastinu m(Figur e1) .A cultur eof the suppuration grew Pseudomonas aeruginosa. Arteriography showe da sacra laneurys mo fth ebrachiocephali carter y(Figur e2). The patient underwent excision of the aneurysm through median resternotomy and extended right collar incision for the diagnosis of mediastinitis and mycotic aneurysm of brachiocephalic artery. The implanted polytetrafluoroethylene graft was found to be filled with pus and was removed. After the sternum had been released from the aneurysm, the wall of which was found to be extremely thin, the aneurysm ruptured suddenly. Cardiopulmonary bypass was quickly instituted through the previously exposed cannulations of the femoral artery and vein, with the ruptured aneurysm compressed by the surgeon’s finger. Selective cerebral perfusion was established with additional cannulations of the right axillary artery and the right atrium. The aneurysm of the brachiocephalic artery was excised under conditions of circulatory arrest with profound hypothermia. A Dacron polyester fabric graft was anastomosed with the tailored aortic arch at the origin of the brachiocephalic artery proximally. The distal anastomosis was at the bifurcation of common carotid artery and subclavian artery, with cardiopulmonary bypass restarted without axillary artery perfusion. Circulatory arrest time was 22 minutes, and the duration of cardiopulmonary bypass was 224 minutes. After the patient was weaned from cardiopulmonary bypass, necrotic sternum was resected and the infected mediastinum was irrigated with povidone iodine. Pedicled

Stiff Man Syndrome With Thymoma

Paraneoplastic stiff man syndrome with a thymoma is rare disease. We treated a 57-year-old woman with a type B1 thymoma, based on the World Health Organization classification, who had stiff man syndrome. Her symptoms were alleviated after a thymectomy. Herein we report a case of stiff man syndrome with a thymoma and also review three cases reported previously.

World Health Organization histologic classification: An independent prognostic factor in resected thymomas

The histologic classification of thymoma remained controversial since 1999, when the World Health Organization (WHO) Consensus Committee published a histologic typing system for tumours of thymus. Clinical features, postoperative relapsing rates, and survival of patients with thymoma were evaluated with reference to the WHO histologic classification, based on a series of 178 patients, submitted to surgery between 1988 and 2000. There were 21 type A, 49 type AB, 45 type B1, 50 type B2 and 13 type B3 tumours. The invasiveness of tumours was 23.8%, 51%, 73.3%, 82% and 100% for types A, AB, B1, B2 and B3 tumours, respectively. The frequency of invasion of the great vessels increased according to the tumour type in the order A (0%), AB (4%), B1 (6.6%), B2 (22%), and B3 (23%). The 10-year disease-free survival was 95%, 90%, 85%, 71% and 40% for types A, AB, B1, B2 and B3, respectively. According to the Masaoka staging system, the disease-free survival rates were 94%, 88% and 66% for stages I, II and III, respectively, at 10 years. No stage IVA thymomas reached 10 years follow-up. Overall survival at 10 years were 88% and 25% when complete and incomplete resection were considered. By multivariate analysis, Masaoka staging system, WHO histologic classification and complete resection were significant independent prognostic factors, whereas age- and sex-associated myasthenia gravis were not. The present study demonstrated the World Health Organization histologic classification a good prognostic factor, such as completeness of surgical resection and Masaoka staging system.

Myasthenia gravis appearing after thymectomy for thymoma

A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.

Adjuvant Radiation of Stage III Thymoma: Is It Necessary?

The criteria for administration of adjuvant radiation therapy after thymoma resection remains controversial, and it is unclear whether patients with Masaoka stage III thymoma benefit from adjuvant radiation. The goal of this report was to determine whether or not this group benefits from radiation therapy in disease-specific survival and disease-free survival. Case records of the Massachusetts General Hospital were retrospectively reviewed from 1972 to 2004. One hundred and seventy-nine patients underwent resection for thymoma, of which 45 had stage III disease. Forty-five stage III patients underwent resection and in 36 it was complete. Thirty-eight stage III patients received radiation therapy. Baseline prognostic factors between radiated and nonradiated groups were similar. The addition of adjuvant radiotherapy did not alter local or distant recurrence rates in patients with stage III thymoma. Disease-specific survival at 10 years in stage III patients who did not receive radiation was 75% (95% confidence interval, 32% to 100%) and in patients who did receive radiation therapy it was 79% (95% confidence interval, 64% to 94%) (p = 0.21). The most common site of relapse was the pleura. Most patients who have stage III thymoma undergo complete resection. Some patients enjoy prolonged disease-free survival without adjuvant radiation after resection of stage III thymoma. Radiation does not seem to prevent pleural recurrences when given after resection of stage III thymomas. The use of routine adjuvant radiation after a complete resection of stage III thymoma needs to be re-addressed. There may be a role for the use of chemotherapy to reduce pleural recurrences.

Repetitive Endoscopic Laser Treatments for Palliation of Lung Malignancies

Endobronchial laser therapy is generally safe and well tolerated. Because the laser is a form of nonionizing radiation, therapy can be repeated as often as needed. Two male patients, 50 and 55 years old, were referred to our clinic because of severe dyspnea and massive hemoptysis, the first 3 years ago and the second 1.5 years ago. In his medical history, the former patient had a thoracotomy for thymoma resection 5 years ago. Rigid bronchoscopy was performed under general anesthesia, Nd:YAP (neodymium-yttrium, aluminum, pevroskite) laser resection and silicon stent insertion were carried out for an endobronchial mass that was almost completely obliterating the left main bronchus. During the next 2 years, the same procedure was repeated 6 times to prevent distal tracheal obliteration. The left lung has now been totally collapsed for 2 years and the patient is still alive and healthy. The latter was a patient with a centrally located nonsmall cell lung cancer invading the middle and lower trachea, right main and upper lobe bronchi causing near-total obstruction. Rigid bronchos-copy was performed under general anesthesia. Nd:YAP laser coagulation and mechanical resection were carried out and a Dumon “Y” stent was inserted. In 1.5 years, therapeutic bronchoscopy was repeated 6 times. The patient is alive without dyspnea or respiratory insufficiency, although with brain metastases. Endoscopic laser resection of lung malignancies is rapid, effective, repeatable, and complementary to other treatments; although it should be considered only palliative, it could be curative in benign lesions and early cancers.

A 41-Year-Old Man With Altered Mental Status and Acute Flaccid Paralysis

A 41-year-old man with a history of thymoma resection was admitted to the hospital with a 3-week history of generalized body aches and fever during late summer. He also reported severe headache for 1 week and photophobia for 3 weeks. He denied any recent travel, sick contacts, insect bites, rash, muscle weakness, or neck stiffness. He reported dizziness and blurred and double vision, and was noted to have an unsteady gait 1 day prior to hospital admission.

Long-term survival and prognostic factors in thymic epithelial tumours.

The aim of this study is to analyze long-term survival and the prognostic significance of some factors after surgical resection of thymic epithelial tumours. We performed a retrospective analysis of clinical and histopathological data on 132 patients operated on for thymic tumours, from 1970 and 2001. Histologic diagnosis based on the new WHO classification system was made by a single pathologist. A univariate and multivariate analysis of prognostic factors predicting survival was carried out. There were: 108 complete resections (81.8%), 12 partial resections (9.1%) and 12 biopsies (9.1%). Overall 5, 10 and 15-year survival rate was 72, 61 and 52.5%, respectively. The Masaoka staging system showed 44 stage I, 18 stage II, 52 stage III and 18 stage IV. Histologic results were: 14 subtype A, 31 AB, 20 B1, 28 B2, 29 B3 and 10 C; the respective proportions of invasive tumour (stage II-IV) was 28.6, 58.1, 50, 75, 86.2 and 100%. There were 16 tumour recurrences (14.8%) of 108 radically resected thymomas, 10 were treated with radical re-resection. In univariate analysis, four prognostic factors were statistically significant: radical resection, Masaoka clinical staging, WHO histologic subtype and resectable tumour recurrence. In multivariate analysis, the independent factors predicting long-term survival were WHO histology and Masaoka stage. The WHO histologic classification seems to be the most significant prognostic factor reflecting the invasiveness of the thymic tumour. Completeness of resection and Masaoka stage I and II assure a better survival. Unresectable recurrence of thymic tumour predicted a worse prognosis.

Myasthenia gravis occurring after resection of thymoma

The aim of this study was to analyses the clinicopathologic features of the patient with myasthenia gravis (MG) occurring after resection of thymoma. Data of 15 patients were collected. The follow-up range from 8 to 178 (average 76.7) months. A retrospective analysis was performed through comparison with data of all 112 cases without MG, which had not occurred MG during our average 5.5 years follow-up, operated for thymoma in same period. The statistics analysis adopted chi(2) and t test. (1) According to Masaoka's classification of thymoma, stage I in 7 cases, stage II in 4, stage III in 4. Histologic Bernatz's classification: lymphocyte predominant type in 4, epithelial type in 3, mixed type in 7, unknown in 1. According to Osserman's classification of MG, grade I in 7, IIa in 4, IIb in 3, III in 1. The MG onset times was the postoperative narcotic waking duration-137 (average 33.9) months, and the average remission time was 30.9 (0.5 - 120) months. (2) 4 cases who occur MG as soon as pull up narcotic tube, all adopted nondepolarizing muscular relaxants. (3) MG was discovered in 3 cases (3/67) during postoperative radiotherapy until a average dosage of 36 Gy was received in average 24 days. (4) The tendency of occurring MG following resection was found in female patients with longer duration of disease, mixed type, larger and later stage thymoma as compared with the thymoma group. The factors including the operation, relatively using overdose relaxation control, choosing unfavorable muscle relaxant and postoperative radiotherapy could induce postoperative MG. An intensive care should be put on the cases with the tendency of occurring postoperative MG.

Acquired rippling muscle disease with myasthenia gravis

Rippling muscle disease (RMD) is a rare disorder that occurs in both familial and sporadic forms. Seven patients have previously been reported with myasthenia gravis and sporadic RMD. There have been conflicting reports of the electrophysiological characteristics of rippling muscles in this acquired form. Another such patient is reported, and the clinical, electrophysiological, and laboratory features of this disorder are described. In addition, this patient had alopecia areata and recurrent metastatic thymoma, years after resection of a benign thymoma. This report emphasizes the clinical manifestations of RMD in association with myasthenia gravis (RMD-MG), and its distinctive features, in this and previously reported patients.

Thoracoscopic thymectomy using anterior chest wall lifting method

We performed a thoracoscopic resection of thymus and thymoma using a novel method whereby the chest wall was lifted by costal hooks placed on the bilateral third ribs. Since the thymus and fat tissue were also elevated, the mediastinal dissection was started at the underlying vessels and pericardium. This technique conforms to the purpose of endoscopic surgery, as it maximizes the operative field and minimizes chest wall trauma. We have applied this approach to benign mediastinal tumor and stage I thymoma with satisfactory results.

130 Resectable thymoma: treatment outcome and prognostic factors in the late adolescent and adult age group

Estudiar el efecto de un programa intensivo de modificación del estilo de vida en los valores de fibrinógeno plasmático en pacientes sin enfermedad cardiovascular, con fibrinógeno elevado y valores normales de colesterol. Analizar si el efecto sobre el fibrinógeno es independiente del efecto sobre los lípidos.Ensayo clínico controlado y aleatorizado.Once áreas básicas de L’Hospitalet de Llobregat y Barcelona.Se incluirá a 436 pacientes, 218 en cada grupo, de 35-75 años, sin enfermedad cardiovascular (cardiopatía isquémica, accidente cerebrovascular y arteriopatía periférica) con hiperfibrinogenemia (fibrinógeno > 300 mg/dl) y colesterol plasmático < 250 mg/dl.Un grupo de pacientes recibirá una intervención intensiva (en frecuencia e intensidad del consejo y tratamiento) sobre cambios de estilo de vida: dejar de fumar, dieta hipocalórica en caso de sobrepeso u obesidad y ejercicio físico. El seguimento del grupo intervención se realizará cada 2 meses. El grupo control seguirá los cuidados habituales.Se determinarán los valores de fibrinógeno plasmático. Además, se registrarán otros acontecimientos de interés (modificación de los factores de riesgo, cambios en la calidad de vida, acontecimientos cardiovasculares y muerte) durante un seguimiento de 2 años.La instauración de una intervención intensiva de prevención primaria (cambios de estilo de vida) en los pacientes que presentan hiperfibrinogenemia podría ser una medida más eficaz que la intervención habitual para reducir las cifras de fibrinógeno plasmático. Además, estas medidas podrían traducirse en una disminución del riesgo cardiovascular y en una mejora de la calidad de vida del paciente.To study the effect of an intensive programme to modify life-style on levels of plasma fibrinogen in patients without cardiovascular pathology, with high fibrinogen and normal cholesterol levels. To analyse whether the effect on fibrinogen is independent, or otherwise, of the effect on lipids.Randomised clinical trial with a control.11 health districts in L’Hospitalet de Llobregat and Barcelona.436 patients will be included, 218 individuals between 35 and 75 years old in each group, and without cardiovascular pathology (ischaemic cardiopathy, cerebral vascular accident or peripheral arteriopathy), with hyperfibrinogenaemia (fibrinogen ›300 mg/dL) and with plasma control ‹250 mg/dL.One group of patients will receive an intensive intervention (in frequency and intensity of counselling and treatment) for life-style changes, i.e. stopping smoking, low-calorie diet in case of overweight or obesity, and physical exercise. The follow-up of the intervention group will be every 2 months. The control group will follow customary treatments.Levels of plasma fibrinogen. In addition, other relevant events will be recorded over a 2-year monitoring period: modification of risk factors, changes in quality of life, cardiovascular events or death.The introduction of an intensive primary prevention intervention (life-style changes) in patients with hyperfibrinogenaemia could be a more effective measure than the habitual intervention for reducing plasma fibrinogen figures. In addition, these measures could be translated into a reduction of cardiovascular risk and an improvement in the patient́s quality of life.

Invited commentary

The CD44 receptor is a transmembrane glycoprotein whose principal ligand is hyaluronate. As such, the CD44 receptor plays a significant role in the anchoring of cells to a basement membrane and in the maintenance of epithelial cell polarity. Altered expression of the CD44 receptor (and its splice-variant isoforms) is known to be associated with tumor progression and metastases in a variety of cancers. Lee and colleagues have now examined CD44 expression in both normal human thymic tissue and in resected thymomas of varying histologic subtypes and clinical stages. Their results show that normal thymic tissue occasionally expresses the CD44 receptor, and typically shows no expression of the CD44v5 and CD44v6 isoforms. In contrast, a significant elevation in the expression of the CD44v5 isoform was observed in the neoplastic cells located in the tumor capsules of thymomas. Moreover; they have demonstrated a positive correlation between CD44v5 expression and the Masaoka stage of the thymomas. Using a proportional hazards model, they have further shown that the increased expression of the CD44v5 isoform is an independent adverse prognosticator in the survival of these patients. From a mechanistic viewpoint, these data suggest that specific alterations in molecules responsible for the maintenance of epithelial integrity do indeed influence the propensity of a malignancy to metastasize. Ultimately, these altered membrane receptors may prove to be useful targets for the directed delivery of chemotherapeutic or immunomodulatory agents. These data also join an increasing body of literature demonstrating the importance of the molecular staging of malignancy. To date, our clinical practice has been largely dictated by the anatomic staging of histologic findings. Lee and colleagues’ data suggest that a patient-specific finding of an altered molecular marker could, a priori, indicate the aggressiveness of an individual thymoma, irrespective of the clinical stage. It is likely within the next decade that the inclusion of molecular staging information into our current pathologic staging paradigms will not only allow us to better define an individual’s prognosis, but also permit us to tailor surgical and nonsurgical interventions to achieve the best clinical outcome.

Prognostic significance of CD44v5 expression in human thymic epithelial neoplasms

Background Cell surface glycoproteins of the CD44 family play roles in cell-cell and cell-matrix interactions. Their aberrant expression has been implicated in tumor invasion and metastasis of a variety of neoplasms, but not, to date, of thymic epithelial tumors. Methods To investigate the expression of CD44 molecules, immunohistochemical staining using monoclonal antibodies against human CD44 standard form (CD44 s) and two common splicing variant (CD44v) isoforms, CD44v5 and CD44v6, was performed on 64 resected thymomas and 20 normal thymuses. These tumors were categorized histologically according to the World Health Organization (WHO) histologic classification, and the pathologic staging was classified according to the definitions of Masaoka. Results The positive expression rates in these patients were as follows: CD44 s (normal thymuses, 10%; thymomas, 22%), CD44v5 (normal thymuses, 0%; thymomas, 67%), and CD44v6 (normal thymuses, 0%; thymomas, 26%). CD44 s and CD44v5 immunoreactivity showed a positive correlation with tumor stages ( p = 0.034 and 0.027, respectively). The CD44v5 expression of neoplastic cells in tumor capsules has significant correlation with tumor stages (II, 5%; III, 70%; IVA, 100%; p < 0.001). On the basis of univariate survival analysis, the Masaoka staging system, WHO histologic classification, and CD44v5 expression showed a statistically significant positive relation to survival ( p < 0.001, 0.002, 0.011, respectively). Using Cox’s regression model, increasing CD44v5 expression, the Masaoka staging, and the WHO classification system were found to be significant independent prognostic factors. Conclusions CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas.

Bilateral Pneumothoraces After Unilateral Transthoracic Needle Biopsy of a Lung Nodule

The occurrence of pneumothorax after an invasive transthoracic procedure is a well-known complication. Less well-recognized is the occurrence of bilateral pneumothoraces after a unilateral intervention with a potential for life-threatening consequences in patients who have undergone median sternotomies. We present a patient who had undergone a thymoma resection in the remote past and developed bilateral pneumothoraces after undergoing transthoracic needle biopsy of a right lung nodule.